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Sample records for 8-hydroxy-2-di-n-propylamino tetralin 8-oh-dpat

  1. The serotonin 5-Hydroxytryptaphan1A receptor agonist, (+)8-hydroxy-2-(di-n-propylamino)-tetralin, stimulates sympathetic-dependent increases in venous tone during hypovolemic shock.

    PubMed

    Tiniakov, Ruslan; Scrogin, Karie E

    2006-11-01

    Adjuvant treatment of hypovolemic shock with vasoconstrictors is controversial due to their propensity to raise arterial resistance and exacerbate ischemia. A more advantageous therapeutic approach would use agents that also promote venoconstriction to augment perfusion pressure through increased venous return. Recent studies indicate that 5-hydroxytryptophan (5-HT)(1A) receptor agonists increase blood pressure by stimulating sympathetic drive when administered after acute hypotensive hemorrhage. Given that venous tone is highly dependent upon sympathetic activation of alpha(2)-adrenergic receptors, we hypothesized that the 5-HT(1A) receptor agonist, (+)8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT), would increase venous tone in rats subject to hypovolemic shock through sympathetic activation of alpha(2)-adrenergic receptors. Systemic administration of 8-OH-DPAT produced a sustained rise in blood pressure (+44 +/- 3 mm Hg 35 min after injection, P < 0.01 versus saline) and mean circulatory filling pressure (+4.2 +/- 0.7 mm Hg, P < 0.01 versus saline) in conscious rats subjected to hypovolemic shock. An equipressor infusion of epinephrine failed to influence mean circulatory filling pressure (MCFP). Ganglionic blockade, alpha(1)-, or peripheral alpha(2)-adrenergic receptor blockade prevented the rise in MCFP observed with 8-OH-DPAT, but only alpha(1)-adrenergic receptor blockade diminished the pressor effect of the drug (P < 0.01). 8-OH-DPAT raises blood pressure in rats in hypovolemic shock through both direct vascular activation and sympathetic activation of alpha(1)-adrenergic receptors. The sympathoexcitatory effect of 8-OH-DPAT contributes to elevated venous tone through concurrent activation of both alpha(1)- and alpha(2)-adrenergic receptors. The data suggest that 5-HT(1A) receptor agonists may provide an advantageous alternative to currently therapeutic interventions used to raise perfusion pressure in hypovolemic shock.

  2. MDMA stimulus generalization to the 5-HT(1A) serotonin agonist 8-hydroxy-2- (di-n-propylamino)tetralin.

    PubMed

    Glennon, R A; Young, R

    2000-07-01

    The abused substance N-methyl-1-(3, 4-methylenedioxyphenyl)-2-aminopropane, or MDMA, serves as a training drug in animals. Because the 5-HT(1A) receptor antagonist NAN-190 has been shown to partially antagonize the MDMA stimulus, and because NAN-190 binds at several different types of receptors, in the present study we examined other agents (e.g., adrenergic, dopaminergic, sigma) in tests of stimulus generalization and stimulus antagonism to determine their influence on the MDMA stimulus. Each of these agents (i.e., clenbuterol, S(-)propranolol, R(+)SCH-23390, amantadine, NANM) was without effect on MDMA-appropriate responding. The finding that NAN-190 behaves as a 5-HT(1A) partial agonist in some studies prompted examination of the 5-HT(1A) receptor agonist 8-OH DPAT and its optical isomers. MDMA-stimulus generalization occurred to racemic 8-OH DPAT (ED(50) = 0.3 mg/kg), R(+)8-OH DPAT (ED(50) = 0.2 mg/kg), and to the 5-HT(1A) receptor partial agonist S(-)8-OH DPAT (ED(50) = 0.4 mg/kg). The results suggest that the MDMA stimulus might possess a 5-HT(1A) component of action. Furthermore, because 8-OH DPAT is known to enhance the stimulus effects of hallucinogens as discriminative stimuli, and because MDMA reportedly enhances the effects of hallucinogenic agents in humans ("flipping," "candy flipping"), this latter MDMA-induced phenomenon might involve a 5-HT(1A) mechanism.

  3. Antagonism by 8-hydroxy-2(di-n-propylamino)tetraline and other serotonin agonists of muscarinic M1-type receptors coupled to inositol phospholipid breakdown in human IMR-32 and SK-N-MC neuroblastoma cells

    SciTech Connect

    Fowler, C.J. Karolinska Institutet ); Ahlgren, P.C. ); O'Neill, C. )

    1991-01-01

    IMR-32 and SK-N-MC cells were found to contain ({sup 3}H)quinuclidinyl benzilate specific binding sites inhibited by pirenzepine in a manner suggesting the presence of both M1-type and M2-type muscarinic receptor recognition sites. Neither cell had detectable ({sup 3}H)8-OH-DPAT binding sites. Carbachol stimulated the rate of inositol phospholipid breakdown in IMR-32 and SK-N-MC human neuroblastoma cells with an EC{sub 50} value of about 50 {mu}M in both cases. Pirenzepine inhibited the carbachol stimulated inositol phospholipid breakdown in both cells with Hill slopes of unity and IC{sub 50} values of 15 nM (IMR-32) and 12 nM (SK-N-MC). The 5-HT{sub 1A} receptor agonist 8-OH-DPAT competitively inhibited carbachol-stimulated inositol phospholipid breakdown with pA{sub 2} values of 5.78 (IMR-32) and 5.61 (SK-N-MC). The 5-HT agonists 5-MeODMT and buspirone at micromolar concentrations inhibited carbachol-stimulated breakdown in IMR-32 cells. The inhibition by 8-OH-DPAT and 5-MeODMT was not affected by preincubation with (-)alprenolol. 5-HT was without effect on either basal or carbachol-stimulated breakdown. It is concluded that IMR-32 and SK-N-MC neuroblastoma cells express muscarinic M1-type but not serotoninergic receptors coupled to phosphoinositide-specific phospholipase C. 8-OH-DPAT acts as a weak antagonist at these muscarinic receptors.

  4. The effects of 8-OH-DPAT on neuroinflammation after sarin exposure in mice.

    PubMed

    Garrett, Teresa L; Joshi, Kaushal; Rapp, Christine M; Chapleau, Molly; Cool, David R; Schlager, John J; Lucot, James B

    2013-08-09

    Poisoning by organophosphate nerve agents can induce seizures which rapidly become refractory to treatment and result in brain damage. Current therapies have only a narrow time frame for effective administration after poisoning. 5-HT1A agonists were tested for efficacy in mice against a seizure-producing combination of the carboxylesterase inhibitor 2-(o-cresyl)-4H-1:3:2-benzodioxaphosphorin-2-oxide (CBDP) and sarin, producing an LD20-40. Administration of the 5-HT1A agonist, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) decreased glial fibrillary acidic protein (GFAP) staining in mice when administered 1min after CBDP and sarin while other 5-HT1A agonists buspirone and S-14506 were not effective. The reduction in GFAP staining by 8-OH-DPAT remained significant when a single dose was administered 2h after the toxic challenge. In addition, 8-OH-DPAT reversed the increase in the inflammatory factor IL-1β in the dentate gyrus and amygdala but did not reduce positive TUNEL staining in the dentate gyrus. Due to the failure of the two other agonists to provide protection, the 5-HT1A antagonist WAY-100635 was tested. WAY-100635 was found to neither reverse the neuroprotective effects of 8-OH-DPAT nor worsen the damage when given alone, making a role for this receptor unlikely. The neuroprotective effects of 8-OH-DPAT appear to lie within its secondary pharmacology.

  5. Effects of (+)-8-OH-DPAT on the duration of immobility during the forced swim test and hippocampal cell proliferation in ACTH-treated rats.

    PubMed

    Miyake, Ayaka; Kitamura, Yoshihisa; Miyazaki, Ikuko; Asanuma, Masato; Sendo, Toshiaki

    2014-07-01

    In the present study, we examined the effect of ACTH on the immobilization of rats in the forced swim test and hippocampal cell proliferation after administration of the 5-HT1A receptor agonist, R-(+)-8-hydroxy-2-di-n-propylamino tetralin ((+)-8-OH-DPAT). Chronic treatment with (+)-8-OH-DPAT (0.01-0.1 mg/kg, s.c.) significantly decreased the duration of immobility in saline- and ACTH-treated rats. Chronic administration of ACTH caused a significant decrease in hippocampal cell proliferation. However, (+)-8-OH-DPAT significantly normalized cell proliferation in ACTH-treated rats. We then investigated the effects of (+)-8-OH-DPAT on the expression of brain-derived neurotrophic factor (BDNF) and cyclin D1 (elements of cyclic adenosine monophosphate response element-binding protein (CREB)-BDNF and Wnt signaling pathways, respectively) in the hippocampus of saline- and ACTH-treated rats. ACTH treatment significantly decreased the expression of cyclin D1, while treatment with (+)-8-OH-DPAT normalized the expression of cyclin D1 in ACTH-treated rats. However, the expression of BDNF did not change in either saline- or ACTH-treated rats. These findings suggest that the antidepressant effects of (+)-8-OH-DPAT in treatment-resistant animals may be attributed to an enhancement of hippocampal cell proliferation, at least in part due to an enhancement of cyclin D1 expression.

  6. Role of 5-HT(1A) and 5-HT(7) receptors in the facilitatory response induced by 8-OH-DPAT on learning consolidation.

    PubMed

    Meneses, A; Terrón, J A

    2001-06-01

    The present study further explored the mechanisms involved in the facilitatory effect induced by (+/-)-8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) on learning consolidation. For this purpose, we analyzed in parallel the effects of LY215840 and ritanserin, two 5-HT(2) receptor antagonists with high affinity for the 5-HT(7) receptor, and WAY100635, a selective 5-HT(1A) receptor antagonist, on the facilitatory effect induced by 8-OH-DPAT on learning consolidation. We also determined whether LY215840 and/or ritanserin could be beneficial in restoring a deficient learning condition. Using the model of autoshaping task, post-training injection of LY215840 or WAY100635 had no effect on learning consolidation. However, both drugs abolished the enhancing effect of 8-OH-DPAT, with LY215840 being slightly more effective than WAY100635 in this respect. Ritanserin produced an increase in performance by itself and also abolished the effect of 8-OH-DPAT. Remarkably, selective blockade of 5-HT(2A) and 5-HT(2B/2C) receptors with MDL100907 and SB200646, respectively, failed to alter the 8-OH-DPAT effect. LY215840 and ritanserin, at the doses that inhibited the 8-OH-DPAT-induced response, reversed the learning deficits induced by scopolamine and dizocilpine. The present results suggest that the enhancing effect produced by 8-OH-DPAT on learning consolidation involves activation of 5-HT(1A) receptors and an additional mechanism, probably related to the 5-HT(7) receptor. Blockade of 5-HT(2) receptors, and perhaps of 5-HT(7) receptors as well, may provide some benefit in reversing learning deficits associated with decreased cholinergic and/or glutamatergic neurotransmission.

  7. Duloxetine and 8-OH-DPAT, but not fluoxetine, reduce depression-like behaviour in an animal model of chronic neuropathic pain.

    PubMed

    Hu, Bing; Doods, Henri; Treede, Rolf-Detlef; Ceci, Angelo

    2016-04-21

    The current study assessed whether antidepressant and/or antinociceptive drugs, duloxetine, fluoxetine as well as (±)-8-hydroxy-2-[di-n-propylamino] tetralin (8-OH-DPAT), are able to reverse depression-like behaviour in animals with chronic neuropathic pain. Chronic constriction injury (CCI) of the sciatic nerve in rats was selected as neuropathic pain model. Mechanical hypersensitivity and depression-like behaviour were evaluated 4 weeks after surgery by "electronic algometer" and forced swimming test (FST), which measured the time of immobility, and active behaviours climbing and swimming. The selective noradrenergic and serotonergic uptake blocker duloxetine (20mg/kg) and the selective 5-HT1A agonist 8-OH-DPAT (0.5mg/kg) significantly reversed both mechanical hypersensitivity and depression-like behaviour in CCI animals. Duloxetine significantly reversed depression-like behaviour in CCI rats by increasing the time of climbing and swimming, while 8-OH-DPAT attenuated depression-like behaviour mainly by increasing the time of swimming. However, the selective serotonergic uptake blocker fluoxetine (20mg/kg) failed to attenuate mechanical hypersensitivity and depression-like behaviour, possibly due to confounding pro-nociceptive actions at 5-HT3 receptors. These data suggest to target noradrenergic and 5-HT1A receptors for treatment of chronic pain and its comorbidity depression.

  8. Comparison of the effects of IVth ventricular administration of some tryptamine analogues with those of 8-OH-DPAT on autonomic outflow in the anaesthetized cat.

    PubMed Central

    Shepheard, S. L.; Jordan, D.; Ramage, A. G.

    1994-01-01

    1 The present study compares the effects on representative autonomic outflows of IVth ventricular application of tryptamine analogues which act at 5-HT1 receptors with 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT). 2 Cumulative doses of 8-OH-DPAT, N,N-di-n-propyl-5-carboxamidotryptamine (DP-5-CT) and 5-carboxamidotryptamine (5-CT, 2.5-40 nmol kg-1), sumatriptan (10-160 nmol kg-1), indorenate (100-800 nmol kg-1), 5-hydroxytryptamine (5-HT, 20-640 nmol kg-1) both alone and in the presence of cinanserin (0.1 mg kg-1) were given into the IVth ventricle of cats which were anaesthetized with a mixture of alpha-chloralose and pentobarbitone sodium, neuromuscularly blocked and artificially ventilated. Recordings were made of arterial blood pressure, heart rate, renal, cardiac, splanchnic and phrenic nerve activities, femoral arterial flow, tracheal and intragastric pressures. 3 Central application of each of the agonists evoked significant falls in arterial blood pressure. In addition 8-OH-DPAT, DP-5-CT, 5-CT and 5-HT all evoked a differential inhibition of sympathetic nerve activities, with renal nerve activity being the most sensitive and cardiac nerve activity the least sensitive. In the dose-ranges used, administration of sumatriptan evoked reductions only in renal and splanchnic nerve activities whilst indorenate reduced activity in all three sympathetic nerves to a similar extent. 4 The effect of the agonists on heart rate was more inconsistent than the effects on sympathetic outflow.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8004405

  9. Effects of 8-OH-DPAT, 5-CT and muscimol on behaviour maintained by a DRL20 schedule of reinforcement, following microinjection into the dorsal or median raphe nuclei.

    PubMed

    Fletcher, P.J.

    1994-06-01

    Experiments were performed to investigate the effects of microinjections of the 5-HT(1A) agonist 8- hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT), the non-selective 5-HT(1) agonist 5-carboxamidotryptamine (5-CT) and the GABA(A) agonist muscimol into the midbrain raphe nuclei, on behaviour maintained by a differential reinforcement of low rate (DRL) 20 schedule of food reinforcement. Following acquisition of responding under the DRL20 schedule, in which responses were reinforced only if they occurred at least 20s after the previous response, two groups of rats were prepared with a stainless steel guide cannula aimed at either the dorsal raphe nucleus or the median raphe nucleus. Injections of 8-OH-DPAT and 5-CT into the median raphe dose-dependently increased responding and reduced the number of reinforcers earned, leading to a net reduction in response efficiency from 45% to approximately 27% (5µg 8-OH-DPAT) and 22% (375ng 5-CT). Both drugs appeared to shift the frequency distribution of inter-response times (IRTs) towards shorter IRTs, and lowered the mean IRT. These effects were not observed after dorsal raphe injections of either drug. This pattern of results, together with results obtained in other paradigms measuring response inhibition, suggests that suppression of the activity of median raphe 5-HT neurones induces deficits in the ability to withhold responding. Muscimol increased responding, decreased the number of reinforcers earned and reduced response efficiency after both dorsal raphe and median raphe injections. These effects were more pronounced following median raphe injections, and were of considerably greater magnitude than those observed following treatment with the 5-HT agonists. Muscimol injected into the median raphe lowered the mean IRT, and increased the frequency of short duration IRTs. Thus, stimulation of GABA(A) receptors within the median raphe induces a pattern of behavioural disruption in the DRL task, that is more severe than that

  10. Mechanism of action of 8-OH-DPAT on learning and memory.

    PubMed

    Meneses, A; Hong, E

    1994-12-01

    It has been previously demonstrated that pretraining injection of 8-hydroxy-2-(di-n-propilamino)tetralin (8-OH-DPAT, a 5-HT1A agonist) impairs conditioned response (CR) in an autoshaping learning task. Therefore, in the present work we intended to determine whether such an effect could be prevented by pretraining, and whether pre- or postsynaptic 5-HT receptors are involved. Groups of rats received or did not receive food magazine training. On the next day, all groups in both conditions, pre- or posttraining, were treated with 8-OH-DPAT (0, 0.062, or 0.250 mg/kg). Posttraining groups were tested on a second session of autoshaping 24 h later. In a second experiment, naive rats received para-chlorophenylalanine (PCPA) (300 mg/kg x 3 days) before pre- or posttraining injection of 8-OH-DPAT. Results showed that in those groups trained to food magazine and treated 24 h later with 8-OH-DPAT, CR was not affected or enhanced. PCPA injection had no effect by itself, but blocked or attenuated the effect of a post- or pretraining injection of 8-OH-DPAT. The present data suggest that a) the pretraining effect of 8-OH-DPAT eliciting a decrease in CR can be eliminated by a food magazine training session; and b) presynaptic 5-HT1A receptors are involved in the effect of 8-OH-DPAT on the acquisition and consolidation of learning.

  11. Stimulation of serotonin-1A receptors in mammals to alleviate motion sickness and emesis induced by chemical agents

    NASA Technical Reports Server (NTRS)

    Lucot, James B. (Inventor); Crampton, George H. (Inventor)

    1990-01-01

    A method for the alleviation of both motion sickness and chemically-induced emesis is provided which includes the administration of a nontoxic, therapeutically effective amount of a composition which stimulates serotonin-1A receptors in a mammal in need of such treatment. The preferred compounds for use are buspirone and 8-hydroxy-2(di-n-propylamino)-tetralin (8-OH-DPAT).

  12. Carotid haemodynamics in pigs during infusions of 8-OH-DPAT: reduction in arteriovenous shunting is mediated by 5-HT1-like receptors.

    PubMed Central

    Bom, A. H.; Verdouw, P. D.; Saxena, P. R.

    1989-01-01

    1. The effects of intracarotid infusions of 8-hydroxy-2-[di-n-propyl-amino]-tetralin (8-OH-DPAT) on heart rate, blood pressure and carotid blood flow and its distribution were studied in anaesthetized pigs by use of radioactive microspheres of 15 microns diameter. 2. Control experiments with physiological saline showed that systemic and carotid haemodynamics remain essentially unchanged during the experimental period. In contrast to results obtained in rat, cat and dog experiments, 8-OH-DPAT did not decrease arterial blood pressure. 3. 8-OH-DPAT, which has a high affinity and is selective for the 5-HT1A recognition site, caused a dose-related decrease in arteriovenous anastomotic (non-nutrient) blood flow, resulting in a decrease in carotid blood flow. At the highest dose used, a small increase in arteriolar (nutrient) blood flow was observed. 4. The decrease in arteriovenous anastomotic and carotid blood flow induced by 8-OH-DPAT was not significantly modified by pretreatment with the 5-HT2 receptor antagonist ketanserin (0.5 mg kg-1), but was markedly reduced by pretreatment with methiothepin (1 mg kg-1), which blocks both the 5-HT1-like and 5-HT2 receptors. 5. It is concluded that the effects of 8-OH-DPAT on arteriovenous anastomotic blood flow are mediated by 5-HT1-like receptors. These receptors, however, cannot yet be classified as belonging to 5-HT1A receptor subtype. Since a number of antimigraine drugs reduce arteriovenous shunting, it is tempting to suggest that 8-OH-DPAT may have similar clinical efficacy. PMID:2522333

  13. 8-OH-DPAT does not interfere with habituation to motion-induced emesis in cats

    NASA Technical Reports Server (NTRS)

    Lucot, James B.; Crampton, George H.

    1991-01-01

    Experiments were performed to determine if suppression of motion-induced emesis (motion sickness) by 8-OH-DPAT altered the development or retention of habituation to the motion stimulus. Cats received 8-OH-DPAT followed by provocative motion on three consecutive treatment days. A drug-free test on the fourth day resulted in an incidence of emesis that was not different from that obtained on the fourth consecutive day of drug-free motion testing. Three consecutive days of treatment with 8-OH-DPAT without motion had no effect on the incidence of motion sickness on the fourth day. It was concluded that suppression of motion sickness by 8-OH-DPAT does not alter the acquisition or retention of habituation.

  14. 8-OH-DPAT suppresses vomiting in the cat elicited by motion, cisplatin or xylazine

    NASA Technical Reports Server (NTRS)

    Lucot, James B.; Crampton, George H.

    1989-01-01

    Vomiting was suppressed in cats pretreated with 8-OH-DPAT and then challenged with an emetic stimulus; motion, xylazine or cisplatin. The antiemetic effect is likely due to stimulation of postsynaptic serotonin-1A receptors. The most parsimonious explanation is that it acts at a convergent structure, presumably at or near the vomiting center. If so, 8-OH-DPAT may block emesis elicited by virtually any other stimulus. A supplementary experiment revealed that lorazepam suppressed motion sickness at a dose that produced ataxia, but did not suppress xylazine-induced emesis. These results do not support the possibility that the antiemetic effects of 8-OH-DPAT were the result of anxiolytic activity.

  15. Modification of 8-OH-DPAT effects on learning by manipulation of the assay conditions.

    PubMed

    Meneses, A; Hong, E

    1994-01-01

    A role for the 5-HT1A receptor in learning and memory has been suggested by diverse evidence. The present paper deals with the acute effect of 8-OH-DPAT (a 5-HT1A agonist) administered to rats before or after training in an autoshaped lever-press response (a model of associative learning). The results show that 8-OH-DPAT improved consolidation of the conditioned response (CR) when injected post-training, but impaired it with pretraining administration. Both effects were time-dependent. When the compound was administered pre- or post-training to free-feeding or prefeeding animals, they did not learn the CR. When it was administered to retrained food-deprived animals, the compound was also inactive. However, with retrained animals on a free-feeding schedule, pre- or post-training administration of 8-OH-DPAT enhanced retrieval in a dose-dependent fashion. Pretraining administration of 8-OH-DPAT impaired food intake and exploration, and therefore learning. The present results strongly suggest a role of 5-HT1A receptors in the consolidation and retrieval of learning. Such improvement is independent of food intake.

  16. 8-OH-DPAT facilitated memory consolidation and increased hippocampal and cortical cAMP production.

    PubMed

    Manuel-Apolinar, L; Meneses, A

    2004-01-05

    Animals were submitted to an associative learning task named Pavlovian/instrumental autoshaping (P/I-A) and treated with selective 5-HT1A and 5-HT7 receptor agonists and antagonists. Next, they were sacrificed, their brains removed, dissected and changes on cortical and hippocampal cyclic adenosine monophosphate (cAMP) production were determined. Results revealed that, the 8-OH-DPAT treatment facilitated memory consolidation of autoshaping and that effect was blocked completely by WAY100635 and partially by DR4004. WAY100635 or DR4004 alone had no effect on autoshaping. The cAMP results were complex and yielded no clear relationship to the memory results. Thus, cortical and hippocampal increased on cAMP production was observed following administration of the 5-HT(1A/7) agonist 8-OH-DPAT. The memory effect was, completely or partially, reversed by the selective antagonists WAY100635 (5-HT1A) or DR4004 (5-HT7), respectively.

  17. Effect of the postsynaptic 5-HT1A receptor antagonist MM-77 on stressed mice treated with 5-HT1A receptor agents.

    PubMed

    Alfredo, Briones-Aranda; Ofir, Picazo

    2005-01-31

    The pharmacological effect of the 5-HT1A receptor ligands, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), indorenate, and buspirone, alone or in combination with the antagonist MM-77, was studied in mice subjected to forced swimming. It was confirmed that this stressful factor produces an anxiolytic-like effect, which is reversed by the mentioned 5-HT1A receptor agonists. Only the 8-OH-DPAT-induced decrease of such an effect could be blocked by the postsynaptic antagonist of the 5-HT1A receptor 1-(2-methoxyphenyl)-4-[(4-succinimido)butyl]-piperazine (MM-77). Stressing by forced swimming seems to induce plastic changes in 5-HT1A receptors, which in turn modify the behavioural actions of 5-HT1A receptor agents.

  18. Sympathetic innervation of the splanchnic region mediates the beneficial hemodynamic effects of 8-OH-DPAT in hemorrhagic shock

    PubMed Central

    Tiniakov, Ruslan; Pahan, Kalipada

    2012-01-01

    Administration of the 5-HT1A receptor agonist, 8-OH-DPAT, improves cardiovascular hemodynamics and tissue oxygenation in conscious rats subjected to hypovolemic shock. This effect is mediated by sympathetic-dependent increases in venous tone. To determine the role of splanchnic nerves in this response, effects of 8-OH-DPAT (30 nmol/kg iv) were measured following fixed-arterial blood pressure hemorrhagic shock (i.e., maintenance of 50 mmHg arterial pressure for 25 min) in rats subjected to bilateral splanchnic nerve denervation (SD). Splanchnic denervation decreased baseline venous tone as measured by mean circulatory filling pressure (MCFP) and accelerated the onset of hypotension during blood loss. Splanchnic denervation did not affect the immediate pressor effect of 8-OH-DPAT but did reverse the drug's lasting pressor effect, as well as its ability to increase MCFP and improve metabolic acidosis. Like SD, adrenal demedullation (ADMX) lowered baseline MCFP and accelerated the hypotensive response to blood withdrawal but also reduced the volume of blood withdrawal required to maintain arterial blood pressure at 50 mmHg. 8-OH-DPAT raised MCFP early after administration in ADMX rats, but the response did not persist throughout the posthemorrhage period. In a fixed-volume hemorrhage model, 8-OH-DPAT continued to raise blood pressure in ADMX rats. However, it produced only a transient and variable rise in MCFP compared with sham-operated animals. The data indicate that 8-OH-DPAT increases venoconstriction and improves acid-base balance in hypovolemic rats through activation of splanchnic nerves. This effect is due, in part, to activation of the adrenal medulla. PMID:22718805

  19. Sympathetic innervation of the splanchnic region mediates the beneficial hemodynamic effects of 8-OH-DPAT in hemorrhagic shock.

    PubMed

    Tiniakov, Ruslan; Pahan, Kalipada; Scrogin, Karie E

    2012-09-01

    Administration of the 5-HT(1A) receptor agonist, 8-OH-DPAT, improves cardiovascular hemodynamics and tissue oxygenation in conscious rats subjected to hypovolemic shock. This effect is mediated by sympathetic-dependent increases in venous tone. To determine the role of splanchnic nerves in this response, effects of 8-OH-DPAT (30 nmol/kg iv) were measured following fixed-arterial blood pressure hemorrhagic shock (i.e., maintenance of 50 mmHg arterial pressure for 25 min) in rats subjected to bilateral splanchnic nerve denervation (SD). Splanchnic denervation decreased baseline venous tone as measured by mean circulatory filling pressure (MCFP) and accelerated the onset of hypotension during blood loss. Splanchnic denervation did not affect the immediate pressor effect of 8-OH-DPAT but did reverse the drug's lasting pressor effect, as well as its ability to increase MCFP and improve metabolic acidosis. Like SD, adrenal demedullation (ADMX) lowered baseline MCFP and accelerated the hypotensive response to blood withdrawal but also reduced the volume of blood withdrawal required to maintain arterial blood pressure at 50 mmHg. 8-OH-DPAT raised MCFP early after administration in ADMX rats, but the response did not persist throughout the posthemorrhage period. In a fixed-volume hemorrhage model, 8-OH-DPAT continued to raise blood pressure in ADMX rats. However, it produced only a transient and variable rise in MCFP compared with sham-operated animals. The data indicate that 8-OH-DPAT increases venoconstriction and improves acid-base balance in hypovolemic rats through activation of splanchnic nerves. This effect is due, in part, to activation of the adrenal medulla.

  20. Role of 5-HT1A receptors in the forced swimming wheel test in reserpine-treated mice.

    PubMed

    Kasahara, K; Nagatani, T; Takao, K; Hashimoto, S

    1993-01-01

    The antidepressant-like effect of 8-hydroxy-2-(di-n-propylamino)tetralin(8-OH-DPAT), a selective 5-HT1A receptor agonist, was studied in the forced swimming wheel test in reserpine-treated mice. 8-OH-DPAT and the antidepressant imipramine, dose-dependently increased the number of turns of a water wheel made by mice. This effect of imipramine (30 mg/kg, i.p.) was enhanced by reserpine treatment 24 hr before the test. The effect of 8-OH-DPAT (0.3 mg/kg, i.p.) was also enhanced in reserpine-treated mice. This enhanced effect of 8-OH-DPAT was blocked by pretreatment with the 5-HT1A receptor antagonists, (-)-propranolol (3 mg/kg, i.p.) and NAN-190 (1 mg/kg, i.p.), but was not blocked by a beta-blocker, (-)-atenolol (3 mg/kg, i.p.). 8-OH-DPAT did not affect locomotor activity in the reserpinized mice and did not affect the reduction of monoamine content induced by reserpine. These results suggest that the effect of 8-OH-DPAT in increasing the number of turns of the wheel made by mice was exerted through a 5-HT1A receptor and that this effect did not reflect only changes in the locomotor activity of the mice.

  1. Daily injections of fluoxetine induce dose-dependent desensitization of hypothalamic 5-HT1A receptors: reductions in neuroendocrine responses to 8-OH-DPAT and in levels of Gz and Gi proteins.

    PubMed

    Raap, D K; Evans, S; Garcia, F; Li, Q; Muma, N A; Wolf, W A; Battaglia, G; Van De Kar, L D

    1999-01-01

    The present studies examined the dose-response relationship of fluoxetine-induced desensitization of hypothalamic postsynaptic 5-HT1A receptors, as measured from the reduced neuroendocrine responses to a 5-HT1A agonist. Because hypothalamic Gz proteins mediate the ACTH and oxytocin responses to 5-HT1A receptor activation, we also determined the effect of fluoxetine on the levels of Gz proteins in the hypothalamus. Rats were injected daily for 14 days with saline or with fluoxetine doses of 0.3, 1, 3, 5, 7. 5, or 10 mg/kg/day. Fluoxetine produced a dose-dependent reduction in the oxytocin, ACTH, and corticosterone responses to the 5-HT1A agonist 8-hydroxy-2-(dipropylamino)tetralin (8-OH-DPAT, 50 micrograms/kg, s.c.). The lowest fluoxetine dose that significantly, although incompletely, reduced the neuroendocrine responses to 8-OH-DPAT was 5 mg/kg/day. The 10 mg/kg/day dose of fluoxetine maximally inhibited all neuroendocrine responses to 8-OH-DPAT. Hypothalamic levels of Gz protein were reduced by both the 7.5 and 10 mg/kg/day doses of fluoxetine, whereas Gi1 protein levels were reduced only after the highest dose (10 mg/kg/day) of fluoxetine. Gi2, Gi3, and Go levels were not reduced by any fluoxetine dose. Cytosolic levels of Gi1 and Gz proteins were unaltered, indicating that reductions in Gz and Gi1 proteins are not caused by a redistribution of the proteins from the membrane into the cytosol. The results from the present study indicate that fluoxetine-induced desensitization of hypothalamic postsynaptic 5-HT1A receptor systems is dose-dependent and may be caused in part by reductions in the hypothalamic levels of Gz proteins.

  2. Buspirone enhances immobility in the forced swim test in mice.

    PubMed

    Kitamura, Y; Nagatani, T

    1996-11-01

    We studied the effects of buspirone and 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) on duration of immobility in mice in the forced swim test. Buspirone [3-10 mg/kg, intraperitoneally (IP)] potently and dose dependently increased the duration of immobility in mice. In contrast, following a single dose of 8-OH-DPAT (1-3 mg/kg, IP), there was a dose-dependent decrease in the duration of immobility. Pretreatment with the 5-HT synthesis inhibitor p-chlorophenylalanine (200 mg/kg, IP, 3 days before further drug treatment) did not alter the effects of buspirone or 8-OH-DPAT. The increase in the duration of immobility induced by buspirone (3 mg/kg, IP) was blocked by NAN-190 [1-(2-methoxyphenyl)-4-(4-[2-phthalimido]butyl)-piperazine hydrobromide, 1 mg/kg, IP], a postsynaptic 5-HT1A receptor antagonist. However, the effect of 8-OH-DPAT (1 mg/kg, IP) was not blocked by NAN-190 (1 mg/kg, IP). The effect of buspirone (3 mg/kg, IP) was blocked by apomorphine (0.3 mg/kg, IP), a dopamine receptor agonist. Based on the results of this study, it is suggested that the effects of buspirone and of 8-OH-DPAT on immobility in the forced swim test may occur through different mechanisms.

  3. Effect of repeated co-treatment with fluoxetine and amantadine on the behavioral reactivity of the central dopamine and serotonin system in rats.

    PubMed

    Rogóz, Zofia; Skuza, Grazyna

    2009-01-01

    In the present study we found that repeated co-treatment with fluoxetine and amantadine for 14 days (but not for 7 days) enhanced the hyperactivity induced by amphetamine or quinpirole (a dopamine D(2/3) agonist), compared to treatment with either drug alone. Whereas repeated co-treatment with fluoxetine and amantadine for 7 days more potently inhibited the behavioral syndrome evoked by the 5-hydroxytryptamine (5-HT)(1A) receptor agonist (+/-)-8-hydroxy-2(di-n-propylamino)-tetralin hydrobromide (8-OH-DPAT), it did not change the action of the 5-HT(2) receptor agonist (+/-)-1-(4-iodo-2,5-dimethoxyphenyl)-2-aminopropane hydrochloride (/+/-/-DOI). The obtained results support the hypothesis that repeated co-treatment with fluoxetine and amantadine may evoke more effective antidepressant activity than treatment with fluoxetine alone. Moreover, our results suggest that 5-HT(1A) receptors are useful targets for the development of more rapidly acting and more effective medication.

  4. [Differences between the effects of indorenate and other 5-HT1A agonists on the rabbit aorta].

    PubMed

    Castillo, C; Rosas-Lezama, M A; Castillo, E F; Larios, F J; Hong, E

    1995-01-01

    The aim of this study was to determine if like buspirone, ipsapirone and 8-hydroxy-2(di-N-propylamino)tetralin (8-OH-DPAT), the alpha 1-adrenoceptors are involved in the responses elicited by indorenate in rabbit aorta. Exception made of ipsapirone, all the 5-HT1A agonists above mentioned contracted aortic rings. The contraction elicited by buspirone and 8-OH-DPAT was blocked with prazosin (alpha 1-adrenergic antagonist), whereas the effect of indorenate was unaffected with this blocker but it was inhibited with ritanserin (5-HT2 antagonist). On the other hand, buspirone, ipsapirone and 8-OH-DPAT but not indorenate relaxed arteries precontracted with methoxamine (alpha 1-adrenergic agonist) and none of the agonists relaxed preparations precontracted with acetylcholine or KCl. The results indicate that buspirone and 8-OH-DPAT are partial alpha 1-adrenoceptor agonists since they elicited contractions which are blocked with prazosin and relaxed only rings precontracted with methoxamine. Ipsapirone behaved as an alpha 1-adrenoceptor antagonist since it showed the relaxant but not the contractile effect. Finally, we found no evidence that indorenate has afinity for alpha 1-adrenoceptors. Contraction elicited by this agonist seems to be mediated by 5-HT2 receptors, inasmuch it was blocked with ritanserin.

  5. Increase in serotonin 5-HT sub 1A receptors in prefrontal and temporal cortices of brains from patients with chronic schizophrenia

    SciTech Connect

    Hashimoto, Takeshi; Nishino, Naoki; Nakai, Hisao; Tanaka, Chikako )

    1991-01-01

    Binding studies with ({sup 3}H)8-hydroxy-2-(di-n-propylamino)tetralin (({sup 3}H)8-OH-DPAT), a specific serotonin{sub 1A} (5-HT{sub 1A}) receptor agonist, were done on the autopsied brains from control subjects and from patients with chronic schizophrenia. In the controls, representative Scatchard plots for the specific ({sup 3}H)8-OH-DPAT bindings in the prefrontal cortex and hippocampus revealed a single component of high affinity binding site. The ({sup 3}H)8-OH-DPAT bindings to the prefrontal cortex and hippocampus were potently inhibited by serotonin and 5-HT{sub 1A} agonists, while other neurotransmitters, 5-HT{sub 2} and 5-HT{sub 3} related compounds did not inhibit the binding. The bindings were decreased in the presence of 0.1mM GTP and 0.1mM GppNHp but not in the presence of 0.1mM GMP. In the prefrontal and temporal cortices of schizophrenics, there was a significant increase in the specific ({sup 3}H)8-OH-DPAT binding, by 40% and 60%, respectively, with no change in the hippocampus, amygdala, cingulum, motor cortex, parietal or occipital cortex, as compared to findings in the controls.

  6. Effects of Thalamic Reticular Nucleus Electrical Stimulation in Rats in a T-maze Perseverative Behavior Model Induced by 8-OH-DPAT.

    PubMed

    Andrade, Pablo; Carrillo-Ruiz, José D; Ramírez, Ylián; Jiménez, Fiacro

    2010-01-01

    Objective. Evaluate the possible decrease of chemically induced perseverative behavior in rats after electrical stimulation at different frequencies in the thalamic reticular nucleus. Material and Methods. A total of 28 male rats were divided in four groups: control, sham, OFF stimulation, and ON stimulation (450 µsec, 1 V, 6 and 120 Hz) that underwent the administration of saline solution and 8-OH-DPAT. The animals were evaluated in a T-maze model in which three choices or more in the same branch are considered as perseverative. Intragroup analysis was done through paired T-student and intergroup analysis through an ANOVA test. Results. The numbers of perseverations mean for the control group were 1.3 before and 1.4 post saline solution injections. Sham group mean of 1.3 pre and 3.4 post 8-OH-DPAT administration; OFF stimulation group 1.1 pre and 3.3 post 8-OH-DPAT administration; and for ON stimulation 1.1 pre and 1.9 post 8-OH-DPAT administration for stimulation at low frequency (6 Hz) and 3.4 at high frequency (120 Hz). Evident intergroup statistical differences were shown (p < 0.01). Conclusions. Electrical stimulation with the low-frequency group was the only group that after manipulation with 8-OH-DPAT showed a decrease in perseverative behavior, even close to baseline.

  7. Effects of serotonin antagonists on motion sickness and its suppression by 8-OH-DPAT in cats

    NASA Technical Reports Server (NTRS)

    Lucot, James B.

    1990-01-01

    The antagonist properties of (-)propranolol, (+)propranolol, metergoline and BMY 7378 on the known effect of 8-OH-DPAT (DPAT) to decrease motion sickness in cats has been evaluated. (-)Propranolol produced a greater decrease in the antiemetic effect of DPAT than did (+)propranolol. Although metergoline produced a decrease in the antiemetic effect of DPAT, the decrease could not be clearly attributed to interactions with 5-HT(1A) receptors because metergoline alone slightly enhanced motion sickness. Depletion of 5-HT with PCPA produced a weaker, nonsignificant enhancement of motion sickness, while mesulergine had no effect. As neither nonspecific 5-HT receptor blockade with metergoline nor depletion of 5-HT mimicked the antiemetic effect of DPAT, it was concluded that DPAT acts on postsynaptic 5-HT(1A) receptors to prevent emesis. BMY 7378 alone decreased the incidence of motion sickness. A dose just below this agonist range did not decrease the effects of DPAT.

  8. The effect of the selective 5-HT1A agonists alnespirone (S-20499) and 8-OH-DPAT on extracellular 5-hydroxytryptamine in different regions of rat brain

    PubMed Central

    Casanovas, J M; Lésourd, M; Artigas, F

    1997-01-01

    We have examined the effects of the systemic administration of the selective 5-HT1A agonist alnespirone (S-20499) on in vivo 5-hydroxytryptamine (5-HT) release in the dorsal raphe nucleus, the median raphe nucleus and four forebrain areas innervated differentially by both (dorsal striatum, frontal cortex, ventral hippocampus and dorsal hippocampus). Alnespirone (0.1–3 mg kg−1, s.c.) dose-dependently reduced extracellular 5-HT in the six areas examined. In forebrain, the maximal reductions occurred in striatum and frontal cortex (maximal reduction to 23 and 29% of baseline, respectively). Those in dorsal and ventral hippocampus were more moderate (to ca 65% of baseline). In contrast, the decrease in 5-HT elicited in the median raphe nucleus was more marked than that in the dorsal raphe nucleus (to ca 30 and 60% of baseline, respectively). The selective 5-HT1A antagonist WAY-100635 (0.5 mg kg−1, s.c.) prevented the decrease in 5-HT induced by alnespirone (0.3 mg kg−1, s.c.) in frontal cortex. 8-OH-DPAT (0.025, 0.1 and 0.3 mg kg−1, s.c.) also reduced extracellular 5-HT in a regionally-selective manner (e.g., to 32% of baseline in striatum and to 69% in dorsal hippocampus at 0.1 mg kg−1, s.c.). In midbrain, 8-OH-DPAT reduced the dialysate 5-HT slightly more in the median than in the dorsal raphe nucleus at all doses examined. Doses of both compounds close to their respective ED50 values (0.3 mg kg−1 alnespirone, 0.025 mg kg−1 8-OH-DPAT) reduced 5-HT to a comparable extent in all regions examined. However, the reductions attained at higher doses were more pronounced for 8-OH-DPAT. These data show that the reduction of 5-HT release elicited by alnespirone and 8-OH-DPAT is more important in forebrain areas innervated by 5-hydroxytryptaminergic neurones of the dorsal raphe nucleus. This regional selectivity seems unlikely to be accounted for by differences in the sensitivity of 5-HT1A autoreceptors controlling 5-HT release, given

  9. The effects of serotonin1A receptor on female mice body weight and food intake are associated with the differential expression of hypothalamic neuropeptides and the GABAA receptor.

    PubMed

    Butt, Isma; Hong, Andrew; Di, Jing; Aracena, Sonia; Banerjee, Probal; Shen, Chang-Hui

    2014-10-01

    Both common eating disorders anorexia nervosa and bulimia nervosa are characteristically diseases of women. To characterize the role of the 5-HT1A receptor (5-HT1A-R) in these eating disorders in females, we investigated the effect of saline or 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) treatment on feeding behavior and body weight in adult WT female mice and in adult 5-HT1A-R knockout (KO) female mice. Our results showed that KO female mice have lower food intake and body weight than WT female mice. Administration of 8-OH-DPAT decreased food intake but not body weight in WT female mice. Furthermore, qRT-PCR was employed to analyze the expression levels of neuropeptides, γ-aminobutyric acid A receptor subunit β (GABAA β subunits) and glutamic acid decarboxylase in the hypothalamic area. The results showed the difference in food intake between WT and KO mice was accompanied by differential expression of POMC, CART and GABAA β2, and the difference in body weight between WT and KO mice was associated with significantly different expression levels of CART and GABAA β2. As such, our data provide new insight into the role of 5-HT1A-R in both feeding behavior and the associated expression of neuropeptides and the GABAA receptor.

  10. Changes of body temperature and extracellular serotonin level in the preoptic area and anterior hypothalamus after thermal or serotonergic pharmacological stimulation of freely moving rats.

    PubMed

    Ishiwata, Takayuki; Saito, Takehito; Hasegawa, Hiroshi; Yazawa, Toru; Otokawa, Minoru; Aihara, Yasutsugu

    2004-10-15

    Although many studies has been shown that serotonin (5-HT) in the preoptic area and anterior hypothalamus (PO/AH) is important for regulating body temperature (Tb), the exact role is not established yet due to conflicting results probably related to experimental techniques or conditions such as the use of anesthesia. The purpose of present study was to clarify the role of 5-HT in the PO/AH using the combined methods of telemetry, microdialysis and high performance liquid chromatography (HPLC), with a special emphasis on the regulation of Tb in freely moving rats. Firstly, we measured changes in Tb and levels of extracellular 5-HT and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) in the PO/AH during cold (5 degrees C) and heat (35 degrees C) exposure. We also perfused fluoxetine (5-HT re-uptake inhibitor) and 8-hydroxy-2-(Di-n-propylamino)tetralin (8-OH-DPAT: 5-HT1A agonist) into the PO/AH. During both exposures, although Tb changed significantly, no significant changes were noted in extracellular levels of 5-HT and 5-HIAA in the PO/AH. In addition, although perfusion of fluoxetine or 8-OH-DPAT into the PO/AH increased or decreased extracellular 5-HT and 5-HIAA levels in the PO/AH respectively, but Tb did not change at all. Our results suggest that 5-HT in the PO/AH may not mediate acute changes in thermoregulation.

  11. A delayed and chronic treatment regimen with the 5-HT1A receptor agonist 8-OH-DPAT after cortical impact injury facilitates motor recovery and acquisition of spatial learning

    PubMed Central

    Cheng, Jeffrey P.; Hoffman, Ann N.; Zafonte, Ross D.; Kline, Anthony E.

    2008-01-01

    An early (i.e., 15 min) single systemic administration of the 5-HT1A receptor agonist 8-OH-DPAT enhances behavioral recovery after experimental traumatic brain injury (TBI). However, acute administration of pharmacotherapies after TBI may be clinically challenging and thus the present study sought to investigate the potential efficacy of a delayed and chronic 8-OH-DPAT treatment regimen. Forty-eight isoflurane-anesthetized adult male rats received either a controlled cortical impact or sham injury and beginning 24 hrs later were administered 8-OH-DPAT (0.1 or 0.5 mg/kg) or saline vehicle (1.0 mL/kg) intraperitoneally once daily until all behavioral assessments were completed. Neurobehavior was assessed by motor and cognitive tests on post-operative days 1–5 and 14–19, respectively. The lower dose of 8-OH-DPAT (0.1 mg/kg) enhanced motor performance, acquisition of spatial learning, and memory retention vs. both the higher dose (0.5 mg/kg) and vehicle treatment (p < 0.05). These data replicate previous findings from our laboratory showing that 8-OH-DPAT improves neurobehavior after TBI, and extend those results by demonstrating that the benefits can be achieved even when treatment is withheld for 24 hrs. A delayed and chronic treatment regimen may be more clinically feasible. PMID:18638506

  12. Evidence for a role of the 5-HT2C receptor in central lipopolysaccharide-, interleukin-1 beta-, and leptin-induced anorexia.

    PubMed

    von Meyenburg, Claudia; Langhans, Wolfgang; Hrupka, Brian J

    2003-03-01

    We examined the role of serotonin (5-HT) and the 5-HT(1A) and 5-HT(2C) receptors in the anorectic effects of centrally administered lipopolysaccharide (LPS), interleukin-1 beta (IL-1 beta), and leptin. Food intake was measured in rats after intracerebroventricular (ICV) injections of LPS (20 ng), IL-1 beta (10 ng), or leptin (1 microg) at lights out, followed by intraperitoneal (IP) injections of either the 5-HT(1A) autoreceptor agonist 8-hydroxy-2-(di-n-propylamino)tetraline (8-OH-DPAT) (125 microg/kg) or the 5-HT(2C) receptor antagonist SB 242084 (0.3 mg/kg) at the onset of anorexia. SB 242084 significantly attenuated the food intake reduction caused by all compounds (all P<.01). IP 8-OH-DPAT attenuated ICV IL-1 beta-induced anorexia (P<.01). We also tested the involvement of the median raphe 5-HT(1A) receptors in peripheral LPS- and IL-1 beta-induced anorexia. Rats were injected intraperitoneally with either LPS (100 microg/kg) or IL-1 beta (2 microg/kg) at lights out, and 8-OH-DPAT (4 nmol) was administered directly into the median raphe nucleus at the onset of anorexia. Median raphe injections of 8-OH-DPAT significantly attenuated both IL-1 beta- and LPS-induced anorexia (both P<.01). These results implicate the 5-HT(2C) receptors in the mediation of central LPS-, IL-1 beta-, and leptin-induced anorexia. Our results also suggest that the midbrain raphe nuclei play a role in mediating the anorectic response to peripheral LPS and IL-1 beta.

  13. The guinea-pig ileum preparation as a model for 5-HT1A receptors: anomalous effects with RS-30199-193.

    PubMed Central

    Small, C.; Brown, C. M.; Redfern, W. S.; Spedding, M.

    1991-01-01

    1. Agents that have high and selective affinity for the 5-HT1A site such as 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) and N,N-dipropyl-5-carboxamidotryptamine (DP5CT) inhibited the responses to field stimulation in guinea-pig ileum preparations; the inhibitory effects were antagonized by methiothepin and spiperone, consistent with effects at the 5-HT1A site. 2. The inhibitory effects of DP5CT were pronounced in Tyrode solution containing low Ca2+ (0.9 mM), but were much less apparent in Tyrode solution containing 1.8 or 5.4 mM Ca2+. 3. Responses to DP5CT were abolished by pretreatment with phorbol dibutyrate (3 microM), whereas the responses to UK14304 were only slightly inhibited. 4. Buspirone and ipsapirone (1 microM) inhibited the responses to field stimulation, and the effects were resistant to idazoxan, but inhibited by 8-OH-DPAT or spiperone. 5. RS-30199-193 (5-chloro-2-methyl-1,2,3,4,8,9,10,10a-octahydronaphth-[1,8-cd]- aze pine hydrochloride) an azepine with high affinity for the 5-HT1A site in rat cerebral cortex in binding experiments, augmented contractions, but did not antagonize the responses to DP5CT or to 8-OH-DPAT. 6. The hybrid compound of RS-30199-193 with buspirone, RS-64459-193 (5-chloro-2-[4-(8-azaspiro[4,5]decane-7,9-dione)-but-1-yl]- 1,2,3,4,8,9,10,10a-octahydronaphth[1,8-cd]-3-azepine hydrochloride) maintained high affinity for the 5-HT1A binding site in rat brain and both inhibited the response to field stimulation and antagonized the responses to 8-OH-DPAT and DP5CT.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1839137

  14. Schizophrenia-like disruptions of sensory gating by serotonin receptor stimulation in rats: effect of MDMA, DOI and 8-OH-DPAT.

    PubMed

    Thwaites, Shane J; Gogos, Andrea; Van den Buuse, Maarten

    2013-11-01

    Schizophrenia pathophysiology is associated with alterations in several neurotransmitter systems, particularly dopamine, glutamate and serotonin (5-HT). Schizophrenia patients also have disruptions in sensory gating, a brain information filtering mechanism in response to repeated sensory stimuli. Dopamine and glutamate have been implicated in sensory gating; however, little is known about the contribution of serotonin. We therefore investigated the effects of several psychoactive compounds that alter serotonergic neuronal activity on event-related potentials (ERP) to paired auditory pulses. Male Sprague-Dawley rats were implanted with cortical surface electrodes to measure ERPs to 150 presentations of two 85 dB bursts of white noise, 500 ms apart (S1 and S2). Saline-treated animals suppressed the response to S2 to less than 50% of S1. In contrast, treatment with the serotonin releaser, MDMA (ecstasy; 2.0mg/kg), the 5-HT2A/2C receptor agonist, DOI (0.5mg/kg), or the 5-HT1A/7 receptor agonist, 8-OH-DPAT (0.5mg/kg), caused an increase in S2/S1 ratios. Analysis of waveform components suggested that the S2/S1 ratio disruption by MDMA was due to subtle effects on the ERPs to S1 and S2; DOI caused the disruption primarily by reducing the ERP to S1; 8-OH-DPAT-induced disruptions were due to an increase in the ERP to S2. These results show that 5-HT receptor stimulation alters S2/S1 ERP ratios in rats. These results may help to elucidate the sensory gating deficits observed in schizophrenia patients.

  15. A behavioural and biochemical study in mice and rats of putative selective agonists and antagonists for 5-HT1 and 5-HT2 receptors.

    PubMed Central

    Goodwin, G. M.; Green, A. R.

    1985-01-01

    Radioligand binding techniques have demonstrated the existence of 5-hydroxytryptamine (5-HT) binding subtypes: 5-HT2, 5-HT1A and 5-HT1B. These techniques have also indicated that certain drugs appear to show sub-type specificity: 8-hydroxy-2-(di-n-propylamino)tetralin(8-OH-DPAT), a 5-HT1A agonist; 5-methoxy-3(1,2,3,6-tetrahydropyridin-4-yl)1-H indole (RU 24969), a 5-HT1B agonist; and ritanserin, a 5-HT2 antagonist. (-)-Propranolol is a 5-HT1 antagonist of uncertain sub-type specificity. An examination has been made in mice and rats of the behavioural and biochemical effects of these drugs to determine whether the binding sites have physiological functions and further characterise the behavioural models. Administration of carbidopa (25 mg kg-1) plus 5-hydroxytryptophan (100 mg kg-1) produced head-twitch behaviour in mice which was antagonized by ritanserin (ED50 = 65 micrograms kg-1) but not (-)-propranolol (20 mg kg-1). 8-OH-DPAT (1-10 mg kg-1 s.c.) and RU 24949 (5 mg kg-1 i.p.) did not produce head-twitch behaviour. 8-OH-DPAT decreased 5-HTP- but not 5-methoxy-N-N-dimethyltryptamine (5 mg kg-1)-induced head-twitch by a (-)-propranolol-insensitive mechanism. Locomotor activity produced in mice by RU 24969 (3 mg kg-1) was antagonized by (-)-propranolol (20 mg kg-1) but not the (+)-isomer. (-)-Propranolol did not antagonize the behaviour induced in rats. In mice, both 8-OH-DPAT and RU 24969 markedly inhibited whole brain 5-HT synthesis and this effect was not antagonized by (-)-propranolol. In rats, 8-OH-DPAT (3 mg kg-1 s.c.) produced all the behavioural changes seen after quipazine (25 mg kg-1). (-)-Propranolol inhibited the behaviour changes produced by both agonists, while ritanserin antagonized the behaviour produced by quipazine but not 8-OH-DPAT. It is concluded, therefore, that the 5-HT1A receptor exists between the 5-HT2 receptor and the behavioural effectors. 8-OH-DPAT (at 20 degrees C ambient temperature) rapidly decreased rat body temperature, an effect

  16. Effects of fenfluramine, 8-OH-DPAT, and tryptophan-enriched diet on the high-ethanol intake by rats bred for susceptibility to stress.

    PubMed

    West, Charles H K; Boss-Williams, Katherine A; Weiss, Jay M

    2011-12-01

    The swim-test susceptible (SUS) line of rats has been bred in our laboratory for the characteristic of reduced motor activity in the swim test following exposure to an acute stressor. Testing of multiple generations of SUS rats has also revealed that they consume large amounts of ethanol voluntarily. As reported for lines of rats that show a propensity for high-ethanol intake, the SUS rats show evidence of low serotonergic function. Because serotonergic function has often been shown to be involved in the regulation of alcohol consumption, here we examined the effects of manipulations of serotonin transmission on intake of ethanol by SUS rats. Fenfluramine, a serotonin-releasing drug, was injected at various doses (0.625, 1.25, 2.5, and 5.0mg/kg) twice per day and ethanol intake was measured using a two-bottle free-choice method. The 8-OH-DPAT, a 5‑HT(1A) agonist, was injected at various doses (0.03125, 0.0625, 0.125, 0.25, 0.5, and 1.0mg/kg) before a 1-h session of exposure to ethanol (single-bottle test, water available the other 23h per day). A diet enriched with 3% tryptophan (TRP), the amino acid precursor for serotonin synthesis, was administered in a restricted feeding schedule (5h per day) with ethanol intake measured the last 4h. Fenfluramine decreased ethanol intake at all doses tested. The 8-OH-DPAT increased ethanol intake at lower doses, presumably acting at autoreceptors, which inhibit serotonergic neurons, and decreased intake at higher doses, presumably acting at postsynaptic 5-HT(1A) receptors. TRP-enriched diet also significantly decreased ethanol intake. Food and water intake were less or unaffected by these three manipulations. With all three manipulations, ethanol intake remained suppressed one or more days after the day of tests that decreased ethanol intake. These data suggest that SUS rats, like many other lines/strains of rodents that consume large amounts of alcohol, show an inverse relationship between serotonin transmission and

  17. Behavioural evidence for a functional interaction between central 5-HT2 and 5-HT1A receptors.

    PubMed Central

    Backus, L. I.; Sharp, T.; Grahame-Smith, D. G.

    1990-01-01

    1. The possibility of 5-HT2 receptor modulation of central 5-HT1A receptor function has been examined using the 5-hydroxytryptamine (5-HT) behavioural syndrome induced by 5-HT1A receptor active drugs in rats. 2. The 5-HT2/5-HTIC antagonist ritanserin (0.1-2 mg kg-1) increased the 5-HT behavioural syndrome induced by submaximally effective doses of 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), 5-methoxy-N,N-dimethyltryptamine (5-MeODMT) and gepirone. 3. Pretreatment with the 5-HT2/5-HT1C antagonist ICI 170,809 (0.25-5 mg kg-1) also enhanced the behavioural syndrome induced by 8-OH-DPAT or 5-MeODMT. 4. The 5-HT2/alpha 1-adrenoceptor antagonist ketanserin in a low dose (0.25 mg kg-1) significantly increased the 5-HT behavioural syndrome induced by 8-OH-DPAT or 5-MeODMT, while in a higher dose (2.5 mg kg-1) this drug decreased the response. Experiments with prazosin indicate that the higher dose of ketanserin might reduce the 5-HT behavioural syndrome through blockade of alpha 1-adrenoceptors. 5. Ritanserin and ICI 170,809 had no effect on apomorphine-induced stereotypy or hyperactivity, indicating that these drugs do not produce non-specific behavioural activation. 6. Ritanserin and ICI 170,809 inhibited quipazine-induced wet dog shakes at doses similar to those enhancing the 5-HT behavioural syndrome. 7. We suggest that ritanserin, ICI 170,809 and ketanserin enhance 5-HT1A agonist-induced behaviour through blockade of an inhibitory 5-HT2 receptor regulating or coupled to 5-HT1A receptor-mediated function. PMID:2145051

  18. The phytocannabinoid, Δ9-tetrahydrocannabivarin, can act through 5-HT1A receptors to produce antipsychotic effects

    PubMed Central

    Cascio, Maria Grazia; Zamberletti, Erica; Marini, Pietro; Parolaro, Daniela; Pertwee, Roger G

    2015-01-01

    Background and Purpose This study aimed to address the questions of whether Δ9-tetrahydrocannabivarin (THCV) can (i) enhance activation of 5-HT1A receptors in vitro and (ii) induce any apparent 5-HT1A receptor-mediated antipsychotic effects in vivo. Experimental Approach In vitro studies investigated the effect of THCV on targeting by 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) of 5-HT1A receptors in membranes obtained from rat brainstem or human 5-HT1A CHO cells, using [35S]-GTPγS and 8-[3H]-OH-DPAT binding assays. In vivo studies investigated whether THCV induces signs of 5-HT1A receptor-mediated antipsychotic effects in rats. Key Results THCV (i) potently, albeit partially, displaced 8-[3H]-OH-DPAT from specific binding sites in rat brainstem membranes; (ii) at 100 nM, significantly enhanced 8-OH-DPAT-induced activation of receptors in these membranes; (iii) produced concentration-related increases in 8-[3H]-OH-DPAT binding to specific sites in membranes of human 5-HT1A receptor-transfected CHO cells; and (iv) at 100 nM, significantly enhanced 8-OH-DPAT-induced activation of these human 5-HT1A receptors. In phencyclidine-treated rats, THCV, like clozapine (i) reduced stereotyped behaviour; (ii) decreased time spent immobile in the forced swim test; and (iii) normalized hyperlocomotor activity, social behaviour and cognitive performance. Some of these effects were counteracted by the 5-HT1A receptor antagonist, WAY100635, or could be reproduced by the CB1 antagonist, AM251. Conclusions and Implications Our findings suggest that THCV can enhance 5-HT1A receptor activation, and that some of its apparent antipsychotic effects may depend on this enhancement. We conclude that THCV has therapeutic potential for ameliorating some of the negative, cognitive and positive symptoms of schizophrenia. PMID:25363799

  19. Systemic treatment with a 5HT1a agonist induces anti-oxidant protection and preserves the retina from mitochondrial oxidative stress.

    PubMed

    Biswal, Manas R; Ahmed, Chulbul M; Ildefonso, Cristhian J; Han, Pingyang; Li, Hong; Jivanji, Hiral; Mao, Haoyu; Lewin, Alfred S

    2015-11-01

    Chronic oxidative stress contributes to age related diseases including age related macular degeneration (AMD). Earlier work showed that the 5-hydroxy-tryptamine 1a (5HT1a) receptor agonist 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT) protects retinal pigment epithelium (RPE) cells from hydrogen peroxide treatment and mouse retinas from oxidative insults including light injury. In our current experiments, RPE derived cells subjected to mitochondrial oxidative stress were protected from cell death by the up-regulation of anti-oxidant enzymes and of the metal ion chaperone metallothionein. Differentiated RPE cells were resistant to oxidative stress, and the expression of genes for protective proteins was highly increased by oxidative stress plus drug treatment. In mice treated with 8-OH-DPAT, the same genes (MT1, HO1, NqO1, Cat, Sod1) were induced in the neural retina, but the drug did not affect the expression of Sod2, the gene for manganese superoxide dismutase. We used a mouse strain deleted for Sod2 in the RPE to accelerate age-related oxidative stress in the retina and to test the impact of 8-OH-DPAT on the photoreceptor and RPE degeneration developed in these mice. Treatment of mice with daily injections of the drug led to increased electroretinogram (ERG) amplitudes in dark-adapted mice and to a slight improvement in visual acuity. Most strikingly, in mice treated with a high dose of the drug (5 mg/kg) the structure of the RPE and Bruch's membrane and the normal architecture of photoreceptor outer segments were preserved. These results suggest that systemic treatment with this class of drugs may be useful in preventing geographic atrophy, the advanced form of dry AMD, which is characterized by RPE degeneration.

  20. Serotonin modifies the spontaneous spiking activity of gracile nucleus neurons in rats: role of 5-HT1A and 5-HT2 receptors.

    PubMed

    Grasso, C; Li Volsi, G; Barresi, M

    2016-06-01

    We tested the effects of microiontophoretic application of serotonin (5-HT) on the firing rate of neurons located in the gracile nucleus (GN) of rats. Application of 5-HT1A and 5-HT2 agonists and antagonists respectively mimicked/ modulated and blocked the effects produced by the amine, respectively. Among the tested neurons, 88.2% modified their background firing activity in the presence of 5-HT. Responsive neurons decreased their mean firing activity (MFA) in 56.7% of cases and increased it in the remaining 43.3%. To ascertain the specificity of the effects induced by 5-HT, we utilized 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) and alpha-methyl-5-hydroxytryptamine (α-MET-5-HT), agonists for 5-HT1A and 5-HT2 receptors, respectively. The microiontophoresis of 8-OH-DPAT modified the background firing rate of all GN neurons (100% of tested neurons) mimicking the decrease of MFA evoked by 5-HT. The application of a-MET-5-HT modified the MFA in 76.9% of tested neurons, decreasing it in 61.5% of cases and increasing in the remaining 23.1%. The decrease of MFA induced by 8-OH-DPAT was antagonized by application of the 5-HT1A receptor antagonist N-[2-[-(2-Methoxyphenyl)-1-piperazinyl]ethyl]-N-2-pyridinylcyclohexanecarboxamide maleate salt (WAY100635), while application of 5-HT2 receptor antagonist ketanserine tartrate (KET) antagonized only the increase of MFA induced by a-MET-5-HT. These results indicate that 5-HT is able to modulate the background firing activity of GN neurons by 5-HT1A and 5-HT2 receptors.

  1. Delta(9)-tetrahydrocannabinol prolongs the immobility time in the mouse forced swim test: involvement of cannabinoid CB(1) receptor and serotonergic system.

    PubMed

    Egashira, Nobuaki; Matsuda, Tomomi; Koushi, Emi; Higashihara, Fuminori; Mishima, Kenichi; Chidori, Shozo; Hasebe, Nobuyoshi; Iwasaki, Katsunori; Nishimura, Ryoji; Oishi, Ryozo; Fujiwara, Michihiro

    2008-07-28

    In the present study, we investigated the effect of Delta(9)-tetrahydrocannabinol (THC), the principal psychoactive component of marijuana, on immobility time during the forced swim test. THC (2 and 6 mg/kg, i.p.) significantly prolonged the immobility time. In addition, THC at the same doses did not significantly affect locomotor activity in the open-field test. The selective cannabinoid CB(1) receptor antagonist rimonabant (3 mg/kg, i.p.) significantly reduced the enhancement of immobility by THC (6 mg/kg). Similarly, the selective serotonin (5-HT) reuptake inhibitor (SSRI) citalopram (10 mg/kg, i.p.) and 5-HT(1A/7) receptor agonist 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT, 0.3 mg/kg, i.p.) significantly reduced this THC-induced effect. Moreover, the selective 5-HT(1A) receptor antagonist N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl) cyclohexane carboxamide dihydrochloride (WAY100635, 1 mg/kg, i.p.) and the postsynaptic 5-HT(1A) receptor antagonist MM-77 (0.1 mg/kg, i.p.) reversed this reduction effect of 8-OH-DPAT (0.3 mg/kg). In contrast, the selective 5-HT(7) receptor antagonist (R)-3-[2-[2-(4-methylpiperidin-1-yl)ethyl]pyrrolidine-1-sulfonyl]phenol hydrochloride (SB269970) had no effect on this reduction effect of 8-OH-DPAT. WAY100635 (1 mg/kg) also reversed the reduction effect of citalopram (10 mg/kg). These findings suggest that the 5-HT(1A) receptors are involved in THC-induced enhancement of immobility.

  2. Selective pharmacological blockade of the 5-HT7 receptor attenuates light and 8-OH-DPAT induced phase shifts of mouse circadian wheel running activity

    PubMed Central

    Shelton, Jonathan; Yun, Sujin; Losee Olson, Susan; Turek, Fred; Bonaventure, Pascal; Dvorak, Curt; Lovenberg, Timothy; Dugovic, Christine

    2015-01-01

    Recent reports have illustrated a reciprocal relationship between circadian rhythm disruption and mood disorders. The 5-HT7 receptor may provide a crucial link between the two sides of this equation since the receptor plays a critical role in sleep, depression, and circadian rhythm regulation. To further define the role of the 5-HT7 receptor as a potential pharmacotherapy to correct circadian rhythm disruptions, the current study utilized the selective 5-HT7 antagonist JNJ-18038683 (10 mg/kg) in three different circadian paradigms. While JNJ-18038683 was ineffective at phase shifting the onset of wheel running activity in mice when administered at different circadian time (CT) points across the circadian cycle, pretreatment with JNJ-18038683 blocked non-photic phase advance (CT6) induced by the 5-HT1A/7 receptor agonist 8-OH-DPAT (3 mg/kg). Since light induced phase shifts in mammals are partially mediated via the modulation of the serotonergic system, we determined if JNJ-18038683 altered phase shifts induced by a light pulse at times known to phase delay (CT15) or advance (CT22) wheel running activity in free running mice. Light exposure resulted in a robust shift in the onset of activity in vehicle treated animals at both times tested. Administration of JNJ-18038683 significantly attenuated the light induced phase delay and completely blocked the phase advance. The current study demonstrates that pharmacological blockade of the 5-HT7 receptor by JNJ-18038683 blunts both non-photic and photic phase shifts of circadian wheel running activity in mice. These findings highlight the importance of the 5-HT7 receptor in modulating circadian rhythms. Due to the opposite modulating effects of light resetting between diurnal and nocturnal species, pharmacotherapy targeting the 5-HT7 receptor in conjunction with bright light therapy may prove therapeutically beneficial by correcting the desynchronization of internal rhythms observed in depressed individuals. PMID:25642174

  3. Selective pharmacological blockade of the 5-HT7 receptor attenuates light and 8-OH-DPAT induced phase shifts of mouse circadian wheel running activity.

    PubMed

    Shelton, Jonathan; Yun, Sujin; Losee Olson, Susan; Turek, Fred; Bonaventure, Pascal; Dvorak, Curt; Lovenberg, Timothy; Dugovic, Christine

    2014-01-01

    Recent reports have illustrated a reciprocal relationship between circadian rhythm disruption and mood disorders. The 5-HT7 receptor may provide a crucial link between the two sides of this equation since the receptor plays a critical role in sleep, depression, and circadian rhythm regulation. To further define the role of the 5-HT7 receptor as a potential pharmacotherapy to correct circadian rhythm disruptions, the current study utilized the selective 5-HT7 antagonist JNJ-18038683 (10 mg/kg) in three different circadian paradigms. While JNJ-18038683 was ineffective at phase shifting the onset of wheel running activity in mice when administered at different circadian time (CT) points across the circadian cycle, pretreatment with JNJ-18038683 blocked non-photic phase advance (CT6) induced by the 5-HT1A/7 receptor agonist 8-OH-DPAT (3 mg/kg). Since light induced phase shifts in mammals are partially mediated via the modulation of the serotonergic system, we determined if JNJ-18038683 altered phase shifts induced by a light pulse at times known to phase delay (CT15) or advance (CT22) wheel running activity in free running mice. Light exposure resulted in a robust shift in the onset of activity in vehicle treated animals at both times tested. Administration of JNJ-18038683 significantly attenuated the light induced phase delay and completely blocked the phase advance. The current study demonstrates that pharmacological blockade of the 5-HT7 receptor by JNJ-18038683 blunts both non-photic and photic phase shifts of circadian wheel running activity in mice. These findings highlight the importance of the 5-HT7 receptor in modulating circadian rhythms. Due to the opposite modulating effects of light resetting between diurnal and nocturnal species, pharmacotherapy targeting the 5-HT7 receptor in conjunction with bright light therapy may prove therapeutically beneficial by correcting the desynchronization of internal rhythms observed in depressed individuals.

  4. 5-HT2 presynaptic receptors mediate inhibition of glutamate release from cerebellar mossy fibre terminals.

    PubMed

    Maura, G; Carbone, R; Guido, M; Pestarino, M; Raiteri, M

    1991-09-17

    'Giant' synaptosomes originating from mossy fibre terminals and having sedimentation properties different from those of standard synaptosomes were obtained from rat cerebellum. Exposure of superfused giant synaptosomes to 15 mM KCl caused the release of endogenous glutamate in a largely (about 80%) calcium-dependent manner. The K(+)-evoked overflow of glutamate was inhibited in a concentration-dependent manner by 5-hydroxytryptamine (5-HT) and by the 5-HT2 receptor agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane HCl (DOI), but not by the 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT). The effects of 5-HT and DOI were quite potent, already reaching significant inhibition (about 25%) at 10 nM. The 5-HT2 receptor antagonist ketanserin counteracted the inhibitory effect of 5-HT. In cerebellar slices, ketanserin increased on its own the calcium-dependent K(+)-evoked release of glutamate and this effect was not prevented by tetrodotoxin (TTX). The results support the idea that cerebellar mossy fibres use glutamate as a transmitter and show that the release of glutamate can be inhibited via presynaptic heteroreceptors of the 5-HT2 type probably localized on the mossy fibre terminals.

  5. Blockade of glucocorticoid receptors with ORG 34116 does not normalize stress-induced symptoms in male tree shrews.

    PubMed

    Van Kampen, Marja; De Kloet, E Ronald; Flügge, Gabriele; Fuchs, Eberhard

    2002-12-20

    Glucocorticoid receptors play an important role in the regulation of the activity of the hypothalamo-pituitary-adrenal axis, and are thought to be involved in the pathophysiology of depressive disorders. The present study investigated the effect of the specific glucocorticoid receptor antagonist ORG 34116 (a substituted 11,21 bisarylsteroid compound) in the tree shrew (Tupaia belangeri) chronic psychosocial stress model, an established animal model for depressive disorders. Animals were stressed for 10 days before treatment with ORG 34116 started (25 mg/kg p.o. for 28 days). Stress induced a decrease in body weight, which just failed significance, whereas ORG 34116 did not affect body weight in stress and control animals. ORG 34116 enhanced the stress-induced increase in the concentration of urinary-free cortisol, although no differences between the different experimental groups existed during the last week of treatment. In stressed animals, ORG 34116 did not affect marking behavior, but decreased locomotor activity. Post mortem analysis of 5-HT(1A) receptors revealed a decreased affinity of 3[H]-8-OH-DPAT (3[H]-8-hydroxy-2-[di-n-propylamino]tetralin) binding sites in the hippocampus of animals treated with the glucocorticoid receptor antagonist. In conclusion, under our experimental conditions, the glucocorticoid receptor antagonist ORG 34116 did not normalize the depressive-like symptoms in the psychosocial stress model of male tree shrews. This finding, however, does not exclude that specific central, neuroendocrine and behavioral features are affected by the compound.

  6. 6-Substituted tricyclic partial ergoline compounds are selective and potent 5-hydroxytryptamine sub 1A receptor agents

    SciTech Connect

    Slaughter, J.L.; Harrington, M.A.; Peroutka, S.J. )

    1990-01-01

    A series of 6 tricyclic partial ergoline derivatives was analyzed using radioligand binding assays. Four agents (LY 178210, LY 254089, LY 197205, and LY 197206) display high affinity for 5-hydroxytryptamine{sub 1A} (5-HT{sub 1A}) receptor binding sites labeled by ({sup 3}H)8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) and display {ge} 150 fold selectivity for the 5-HT{sub 1A} over the 5-HT{sub 1D} receptor binding site. The most potent agent investigated, LY 178210, is essentially inactive at a total of 12 other neurotransmitter receptor binding sites in the brain. Using a forskolin-stimulated adenylate cyclase assay as a model of 5-HT{sub 1A} receptor function, LY 178210 was found to display partial agonist activity which was blocked by 10{sup {minus}5} M ({minus})pindolol. These data indicate that LY 178210 is a potent and selective 5-HT{sub 1A} receptor partial agonist.

  7. Evidence for excitatory 5-HT2-receptors on rat brainstem neurones.

    PubMed Central

    Davie, M.; Wilkinson, L. S.; Roberts, M. H.

    1988-01-01

    1. The technique of microiontophoresis was used to investigate the identity of the receptor mediating the excitatory effects of 5-hydroxytryptamine (5-HT) upon neurones in the midline of the medullary brainstem of the rat in vivo. 2. The 5-HT1-like receptor agonists 5-carboxamidotryptamine (5-CT) and 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) failed to excite the majority of neurones excited by 5-HT. The mobilities of 5-CT and 8-OH-DPAT when tested in vitro were found not to differ significantly from that of 5-HT, suggesting that the lack of effect of these agonists was not due to a lower rate of release from the microelectrodes. 3. The excitatory responses to 5-HT were attenuated by the 5-HT 2-receptor antagonists ketanserin and methysergide when applied microiontophoretically or administered intravenously (0.3 and 1 mg kg-1 respectively). Excitatory responses to glutamate and noradrenaline were not reduced. 4. The 5-HT3-receptor antagonist MDL 72222 failed to attenuate selectively the excitatory response to 5-HT when applied either by microiontophoresis or administered intravenously (1 mg kg-1). 5. Microiontophoretic application of the alpha 1-adrenoceptor antagonist prazosin did not attenuate excitatory responses to either 5-HT or noradrenaline. Intravenously administered prazosin (0.8 mg kg-1) also failed to attenuate excitatory responses to 5-HT, but did block excitatory responses to noradrenaline. 6. These results suggest that 5-HT2-receptors, but not 5-HT1-like receptors, 5-HT3-receptors or alpha 1-adrenoceptors, are involved in the excitatory response of midline medullary neurones to 5-HT. PMID:3395786

  8. Effects of 5-HT1A receptor agonists and L-5-HTP in Montgomery's conflict test.

    PubMed

    Söderpalm, B; Hjorth, S; Engel, J A

    1989-01-01

    The effects of the pyrimidinyl-piperazines buspirone, gepirone, ipsapirone and their common metabolite 1-(2-pyrimidinyl)-piperazine (PmP) as well as of 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) and L-5-hydroxytryptophan (L-5-HTP) were investigated in Montgomery's conflict test--an animal anxiety model based on the animal's inborn urge to explore a new environment and its simultaneous fear of elevated, open spaces. Subcutaneous buspirone (32-128 nmol/kg), gepirone (32-128 nmol/kg), ipsapirone (32-512 nmol/kg) and 8-OH-DPAT (50-200 nmol/kg), as well as intraperitoneal L-5-HTP (56 mumol/kg) produced anxiolytic-like effects. However, at higher doses the magnitude of these effects decreased and overall the dose-response curves displayed inverted U-shapes. The highest doses (2048 nmol/kg) of buspirone and of gepirone even decreased responding below control levels, possibly in part due to concomitant sedation/motor impairment. After L-5-HTP (448 mumol/kg) and PmP (512 nmol/kg) anxiogenic-like effects were observed. The results indicate that anxiolytic- and anxiogenic-like effects of drugs affecting central serotonergic neurotransmission can be obtained in a sensitive rat anxiety model which neither involves consummatory behavior nor punishment. The anxiolytic-like effects of these compounds may be due to their 5-HT1A agonistic properties. Moreover, the present data may provide support for a possible reciprocal association of presynaptic 5-HT1A receptors vs. postsynaptic 5-HT1A as well as 5-HT2 receptors with regard to anxiety.

  9. The presence of a serotonin uptake inhibitor alters pharmacological manipulations of serotonin release.

    PubMed

    Kreiss, D S; Wieland, S; Lucki, I

    1993-01-01

    The present study investigated the effects of the presence of the serotonin uptake inhibitor citalopram in the perfusion medium on pharmacological manipulations which increased and decreased striatal serotonin release using in vivo microdialysis. A high performance liquid chromatography detection system equipped with a microbore column was used which reduced the detection limit to 0.5 fmol serotonin/5 microliters sample and enabled basal striatal serotonin release to be measured without the addition of a serotonin uptake inhibitor to the perfusion medium. Although serotonin uptake inhibitors have frequently been used to enhance the serotonin content of dialysate samples, the effects of the presence of serotonin uptake inhibitors on pharmacological manipulations which increased and decreased the release of serotonin have not yet been characterized. Serotonin release was reduced by the systemic administration of the 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT). Although 5-HT release was reduced by 8-OH-DPAT after the addition of citalopram, the 5-HT1A receptor agonist did not reduce absolute levels of extracellular serotonin below basal values of serotonin measured in the absence of citalopram. In addition, citalopram dramatically prevented the four-fold increase in the release of serotonin produced by the systemic administration of the serotonin-releasing agent fenfluramine. The blockade of fenfluramine's effects by citalopram supports the hypothesis that transport of fenfluramine into serotonergic neurons is necessary to increase serotonin release. This study demonstrates that the use of an HPLC detection system equipped with a microbore column can reliably measure basal serotonin release using in vivo microdialysis.(ABSTRACT TRUNCATED AT 250 WORDS)

  10. 5-HT1A-receptor agonist modified amygdala activity and amygdala-associated social behavior in a valproate-induced rat autism model.

    PubMed

    Wang, Chao-Chuan; Lin, Hui-Ching; Chan, Yun-Han; Gean, Po-Wu; Yang, Yen Kung; Chen, Po See

    2013-10-01

    Accumulating evidence suggests that dysfunction of the amygdala is related to abnormal fear processing, anxiety, and social behaviors noted in autistic spectrum disorders (ASDs). In addition, studies have shown that disrupted brain serotonin homeostasis is linked to ASD. With a valproate (VPA)-induced rat ASD model, we investigated the possible role of amygdala serotonin homeostasis in autistic phenotypes and further explored the underlying mechanism. We first discovered that the distribution of tryptophan hydroxylase immunoreactivity in the caudal raphe system was modulated on postnatal day (PD) 28 of the VPA-exposed offspring. Then, we found a significantly higher serotonin transporter availability in the amygdala of the VPA-exposed offspring on PD 56 by using single photon emission computed tomography and computed tomography co-registration following injection of (123)I-labeled 2-((2-(dimethylamino)methyl)phenyl)thio)-5-iodophenylamine((123)I[ADAM]). Furthermore, treatment with 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), a 5-HT1A receptor agonist, increased social interaction and improved fear memory extinction in the VPA-exposed offspring. 8-OH-DPAT treatment also reversed the characteristics of miniature excitatory post-synaptic currents as well as paired pulse facilitation observed in lateral amygdala slices. These results provided further evidence to support the role of the amygdala in characteristic behavioral changes in the rat ASD model. The serotonergic projections that modulate the amygdala function might play a certain role in the development and treatment of behavioral symptoms exhibited in individuals with ASD.

  11. 5-HT1A receptor-responsive pedunculopontine tegmental neurons suppress REM sleep and respiratory motor activity.

    PubMed

    Grace, Kevin P; Liu, Hattie; Horner, Richard L

    2012-02-01

    Serotonin type 1A (5-HT(1A)) receptor-responsive neurons in the pedunculopontine tegmental nucleus (PPTn) become maximally active immediately before and during rapid eye movement (REM) sleep. A prevailing model of REM sleep generation indicates that activation of such neurons contributes significantly to the generation of REM sleep, and if correct then inactivation of such neurons ought to suppress REM sleep. We test this hypothesis using bilateral microperfusion of the 5-HT(1A) receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT, 10 μm) into the PPTn; this tool has been shown to selectively silence REM sleep-active PPTn neurons while the activity of wake/REM sleep-active PPTn neurons is unaffected. Contrary to the prevailing model, bilateral microperfusion of 8-OH-DPAT into the PPTn (n = 23 rats) significantly increased REM sleep both as a percentage of the total recording time and sleep time, compared with both within-animal vehicle controls and between-animal time-controls. This increased REM sleep resulted from an increased frequency of REM sleep bouts but not their duration, indicating an effect on mechanisms of REM sleep initiation but not maintenance. Furthermore, an increased proportion of the REM sleep bouts stemmed from periods of low REM sleep drive quantified electrographically. Targeted suppression of 5-HT(1A) receptor-responsive PPTn neurons also increased respiratory rate and respiratory-related genioglossus activity, and increased the frequency and amplitude of the sporadic genioglossus activations occurring during REM sleep. These data indicate that 5-HT(1A) receptor-responsive PPTn neurons normally function to restrain REM sleep by elevating the drive threshold for REM sleep induction, and restrain the expression of respiratory rate and motor activities.

  12. Galanin (1-15) enhances the antidepressant effects of the 5-HT1A receptor agonist 8-OH-DPAT: involvement of the raphe-hippocampal 5-HT neuron system.

    PubMed

    Millón, Carmelo; Flores-Burgess, Antonio; Narváez, Manuel; Borroto-Escuela, Dasiel O; Santín, Luis; Gago, Belen; Narváez, José Angel; Fuxe, Kjell; Díaz-Cabiale, Zaida

    2016-12-01

    Galanin N-terminal fragment (1-15) [GAL(1-15)] is associated with depression-related and anxiogenic-like effects in rats. In this study, we analyzed the ability of GAL(1-15) to modulate 5-HT1A receptors (5-HT1AR), a key receptor in depression. GAL(1-15) enhanced the antidepressant effects induced by the 5-HT1AR agonist 8-OH-DPAT in the forced swimming test. These effects were stronger than the ones induced by Galanin (GAL). This action involved interactions at receptor level since GAL(1-15) affected the binding characteristics and the mRNA levels of 5-HT1AR in the dorsal hippocampus and dorsal raphe. The involvement of the GALR2 was demonstrated with the GALR2 antagonist M871. Proximity ligation assay experiments indicated that 5-HT1AR are in close proximity with GALR1 and GALR2 in both regions and in raphe RN33B cells. The current results indicate that GAL(1-15) enhances the antidepressant effects induced by 8-OH-DPAT acting on 5-HT1AR operating as postjunctional or as autoreceptors. These results may give the basis for the development of drugs targeting potential GALR1-GALR2-5-HT1AR heteroreceptor complexes linked to the raphe-hippocampal 5-HT neurons for the treatment of depression.

  13. Discriminative stimulus properties of indorenate, a serotonin agonist.

    PubMed Central

    Velázquez-Martínez, D N; López Cabrera, M; Sánchez, H; Ramírez, J I; Hong, E

    1999-01-01

    OBJECTIVE: To determine whether indorenate, a serotonin-receptor agonist, can exert discriminative control over operant responses, to establish the temporal course of discriminative control and to compare its stimulus properties to a (5-HT)IA receptor agonist. [3H]-8-hydroxy-2-(di-N-propylamino) tetralin (8-OH-DPAT). DESIGN: Prospective animal study. ANIMALS: Ten male Wistar rats. INTERVENTIONS: Rats were trained to press either of 2 levers for sucrose solution according to a fixed ratio schedule, which was gradually increased. Rats were given injections of either indorenate or saline solution during discrimination training. Once they had achieved an 83% accuracy rate, rats underwent generalization tests after having received a different dose of indorenate, the training dose of indorenate at various intervals before the test, various doses of 8-OH-DPT, or NAN-190 administered before indorenate or 8-OH-DPAT. OUTCOME MEASURES: Distribution of responses between the 2 levers before the first reinforcer of the session, response rate for all the responses in the session, and a discrimination index that expressed the drug-appropriate responses as a proportion of the total responses. RESULTS: Indorenate administration resulted in discriminative control over operant responses, maintained at fixed ratio 10, at a dose of 10.0 mg/kg (but not 3.0 mg/kg). When the interval between the administration of indorenate and the start of the session was varied, the time course of its cue properties followed that of its described effects on 5-HT turnover. In generalization tests, the discrimination index was a function of the dose of indorenate employed; moreover, administration of 8-OH-DPAT (from 0.1 to 1.0 mg/kg) fully mimicked the stimulus properties of indorenate in a dose-dependent way. The (5-HT)IA antagonist NAN-190 prevented the stimulus generalization from indorenate to 8-OH-DPAT. Also, NAN-190 antagonized the stimulus control of indorenate when administered 45 minutes before

  14. Synthesis and molecular modeling of new 1-aryl-3-[4-arylpiperazin-1-yl]-1-propane derivatives with high affinity at the serotonin transporter and at 5-HT(1A) receptors.

    PubMed

    Orús, Lara; Pérez-Silanes, Silvia; Oficialdegui, Ana-M; Martínez-Esparza, Javier; Del Castillo, Juan-C; Mourelle, Marisa; Langer, Thierry; Guccione, Salvatore; Donzella, Giuseppina; Krovat, Eva M; Poptodorov, Konstantin; Lasheras, Berta; Ballaz, Santiago; Hervías, Isabel; Tordera, Rosa; Del Río, Joaquín; Monge, Antonio

    2002-09-12

    It has been proposed that 5-HT(1A) receptor antagonists augment the antidepressant efficacy of selective serotonin (5-HT) reuptake inhibitors. In a search toward new and efficient antidepressants, 1-(aryl)-3-[4-arylpiperazin-1-yl]-1-propane molecular hybrids were designed, synthesized, and evaluated for 5-HT reuptake inhibition and 5-HT(1A) receptor affinity. The design was based in coupling structural moieties related to inhibition of serotonin reuptake, such as benzo[b]thiophene derivatives to arylpiperazines, typical 5-HT(1A) receptor ligands. In binding studies, several compounds showed affinity at the 5-HT transporter and at 5-HT(1A) receptors. Molecular modeling studies predicted the pharmacophore elements required for high affinity binding and the features that enable to discriminate between agonist, partial agonist, or antagonist action at 5-HT(1A) receptors and 5-HT transporter inhibition. Solvent interactions in desolvation prior to the binding step along with enthalpy and enthropy compensations might be responsible to explain agonist, partial agonist, and antagonist character. Hydrogen-bonding capability seems to be important to break hydrogen interhelical hydrogen bonds or alternatively to form other bonds upon ligand binding. Partial agonists and antagonists are unable to do this as the full agonist, which interacts closely by long-range forces or directly. The compounds showing the higher affinity at both the 5-HT transporter (K(i) < 50 nM) and the 5-HT(1A) receptors (K(i) < 20 nM) were further explored for their ability to stimulate [(35)S]GTPgammaS binding or to antagonize 8-hydroxy-2-di-n-propylamino-tetralin (8-OH-DPAT)-stimulated [(35)]GTPgammaS binding to rat hippocampal membranes, an index of agonist/antagonist action at 5-HT(1A) receptors, respectively. Compound 8g exhibited agonist activity (EC(50) = 30 nM) in this assay, whereas compounds 7g and 8h,i behaved as weak partial agonists and 7h-j and 8j,l antagonized the R(+)-8-OH-DPAT

  15. Effects on serotonin of (-)nicotine and dimethylphenylpiperazinium in the dorsal raphe and nucleus accumbens of freely behaving rats.

    PubMed

    Ma, Z; Strecker, R E; McKenna, J T; Thakkar, M M; McCarley, R W; Tao, R

    2005-01-01

    The aim of this study was to investigate the neurochemical mechanism underlying the effect of nicotine and dimethylphenylpiperazinium (DMPP) on 5-hydroxytryptamine (5-HT) release in the dorsal raphe nucleus and nucleus accumbens of freely behaving rats. For comparison, lobeline, cytisine and RJR-2403 were also investigated. It was found that all drugs, when infused locally, evoked an increase of 5-HT in the dorsal raphe nucleus. However, the magnitudes of the 5-HT increase were comparatively different between the drugs in the ranking of their potency: DMPP>RJR 2403>nicotine>lobeline>cytisine. Both methyllycaconitine, a nicotinic acetylcholine receptor (nAChR) antagonist and methyllycaconitine, a selective alpha7-containing nAChR antagonist blocked the effects of nicotine and DMPP, suggesting that alpha7 subunit mediated the increases in 5-HT. However, DMPP was reported to increase 5-HT using non-nAChR mechanism [Lendvai B, Sershen H, Lajtha A, Santha E, Baranyi M, Vizi ES (1996) Differential mechanisms involved in the effect of nicotinic agonists DMPP and lobeline to release [3H]5-HT from rat hippocampal slices. Neuropharmacology 35:1769-1777]. To test if 5-HT carriers were involved, a selective 5-HT reuptake inhibitor citalopram (1 microM) was infused into the dorsal raphe nucleus before administration of nicotine or DMPP. As a result, citalopram significantly blocked the effect of DMPP, whereas it had no influence on nicotine. Finally, the 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) was used to test whether the increases in 5-HT were depolarization-dependent. Administration of 8-OH-DPAT (0.1 mg/kg, s.c.) produced significant decreases in 5-HT in the animals treated with nicotine. In contrast, the effect of DMPP was not altered by 8-OH-DPAT, suggesting that the increases in 5-HT were independent of cell membrane depolarization. In conclusion, there are different mechanisms involved in nicotine- and DMPP-evoked increases in 5-HT. This

  16. 5-HT1 agonists reduce 5-hydroxytryptamine release in rat hippocampus in vivo as determined by brain microdialysis.

    PubMed Central

    Sharp, T.; Bramwell, S. R.; Grahame-Smith, D. G.

    1989-01-01

    1. An intracerebral perfusion method, brain microdialysis, was used to assess changes of 5-hydroxytryptamine (5-HT) release in the ventral hippocampus of the chloral hydrate-anaesthetized rat in response to systemic administration of a variety of 5-HT1 receptor agonists. 2. A stable output of reliably detectable endogenous 5-HT was measured in dialysates collected from ventral hippocampus with the 5-HT reuptake inhibitor, citalopram, present in the perfusion medium. 3. Under these conditions the putative 5-HT1A agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) caused a dose-dependent (5-250 micrograms kg-1, s.c.) reduction of 5-HT in hippocampal dialysates. 4. Similarly, the putative 5-HT1A agonists gepirone (5 mg kg-1, s.c.), ipsapirone (5 mg kg-1, s.c.) and buspirone (5 mg kg-1, s.c.) markedly reduced levels of 5-HT in hippocampal perfusates whereas their common metabolite 1-(2-pyrimidinyl) piperazine (5 mg kg-1, s.c.), which does not bind to central 5-HT1A recognition sites, had no effect. 5. 5-Methoxy-3-(1,2,3,6-tetrahydro-4-pyridinyl)-1H-indole (RU 24969), a drug with reported high affinity for brain 5-HT1B binding sites, also produced a dose-dependent (0.25-5 mg kg-1, s.c.) decrease of hippocampal 5-HT output. 6. These data are direct biochemical evidence that systemically administered putative 5-HT1A and 5-HT1B agonists markedly inhibit 5-HT release in rat ventral hippocampus in vivo. PMID:2466516

  17. Effects of standardized extracts of St. John's wort on the single-unit activity of serotonergic dorsal Raphe neurons in awake cats: comparisons with fluoxetine and sertraline.

    PubMed

    Fornal, C A; Metzler, C W; Mirescu, C; Stein, S K; Jacobs, B L

    2001-12-01

    St. John's wort is widely used as an herbal remedy for depression. Although its mechanism of action remains unknown, some evidence suggests that St. John's wort might act via brain serotonin (e.g., as a serotonin reuptake inhibitor). To determine whether St. John's wort affects the central serotonergic system, we monitored the discharge rate of serotonin-containing neurons in the dorsal raphe nucleus of awake cats following systemic administration of two clinical preparations of St. John's wort, Jarsin 300 (15-600 mg/kg, p.o.) and Hyperforat (0.5-4.0 ml, i.v.). Both preparations were found to have no effect on neuronal activity. This contrasts sharply with the action of fluoxetine and sertraline (2 mg/kg, p.o.), two selective serotonin reuptake inhibitors (SSRIs), which markedly depressed neuronal activity by increasing the synaptic availability of serotonin at inhibitory somatodendritic 5-HT(1A) autoreceptors. The failure of St. John's wort to depress neuronal activity cannot be attributed to an impairment of the 5-HT(1A) autoreceptor mechanism, since pretreatment with Jarsin 300 (300 mg/kg, p.o.) did not alter the responsiveness of serotonergic neurons to the 5-HT(1A) agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) (10 microg/kg, i.v.). Overall, these findings indicate that the mode of action of St. John's wort is different from that of conventional antidepressant drugs, which elevate brain serotonin and evoke negative feedback control of serotonergic neurons.

  18. Characterization of the 5-HT receptor subtypes involved in the motor behaviours produced by intrathecal administration of 5-HT agonists in rats.

    PubMed Central

    Fone, K. C.; Robinson, A. J.; Marsden, C. A.

    1991-01-01

    1. The motor behavioural effects of intrathecal injections of 5-hydroxytryptamine (5-HT) and a variety of 5-HT receptor agonists were examined in adult Wistar rats to establish; (a) which 5-HT receptor subtype/s elicit each behaviour and (b) whether these receptors are located within the spinal cord. 2. Intrathecal injection of 5-methoxy-N,N'-dimethyltryptamine (5-MeODMT), (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane hydrochloride (DOI) or 2,5-dimethoxy-alpha,4-dimethylbenzene ethamine hydrochloride (DOM) produced dose-related back muscle contractions (BMC) and wet dog shakes (WDS) which were both markedly attenuated by intraperitoneal pretreatment with either ritanserin (1 mg kg-1), ketanserin (0.16 mg kg-1) or mianserin (0.6 mg kg-1) indicating the involvement of 5-HT2 receptors in both these motor behaviours. Both fluoxetine (1-20 mg kg-1, i.p.) and high doses of 5-HT (50 micrograms) following fluoxetine (5 mg kg-1, i.p.) also elicited BMC, further confirming the involvement of 5-HT in this behaviour. 3. Intrathecal 5-carboxamidotryptamine (5-CT) evoked a marked wet-dog shake response without producing any BMC. Intrathecal pretreatment with 8-hydroxy-2-(di-n-propylamino)tetraline (8-OH-DPAT) enhanced, while in contrast 2-methyl-5-HT pretreatment attenuated, 5-HT agonist-induced BMC without affecting WDS. These data suggest that the spinal 5-HT2 receptors mediating BMC are positively modulated by 5-HT1A but negatively influenced by 5-HT3 receptor activation and may be of a different subtype to the supra-spinal 5-HT2 receptors which elicit WDS.(ABSTRACT TRUNCATED AT 250 WORDS) Images Figure 1 Figure 5 PMID:1832068

  19. Multiple receptor subtypes mediate the effects of serotonin on rat subfornical organ neurons

    NASA Technical Reports Server (NTRS)

    Scrogin, K. E.; Johnson, A. K.; Schmid, H. A.

    1998-01-01

    The subfornical organ (SFO) receives significant serotonergic innervation. However, few reports have examined the functional effects of serotonin on SFO neurons. This study characterized the effects of serotonin on spontaneously firing SFO neurons in the rat brain slice. Of 31 neurons tested, 80% responded to serotonin (1-100 microM) with either an increase (n = 15) or decrease (n = 10) in spontaneous activity. Responses to serotonin were dose dependent and persisted after synaptic blockade. Excitatory responses could also be mimicked by the 5-hydroxytryptamine (5-HT)2A/2C receptor agonist 2,5-dimethoxy-4-iodoamphetamine (DOI; 1-10 microM) and could be blocked by the 5-HT2A/2C-receptor antagonist LY-53,857 (10 microM). LY-53,857 unmasked inhibitory responses to serotonin in 56% of serotonin-excited cells tested. Serotonin-inhibited cells were also inhibited by the 5-HT1A-receptor agonist 8-hydroxy-2(di-n-propylamino)tetralin (8-OH-DPAT; 1-10 microM; n = 7). The data indicate that SFO neurons are responsive to serotonin via postsynaptic activation of multiple receptor subtypes. The results suggest that excitatory responses to serotonin are mediated by 5-HT2A or 5-HT2C receptors and that inhibitory responses may be mediated by 5-HT1A receptors. In addition, similar percentages of serotonin-excited and -inhibited cells were also sensitive to ANG II. As such the functional relationship between serotonin and ANG II in the SFO remains unclear.

  20. Motor effects of the non-psychotropic phytocannabinoid cannabidiol that are mediated by 5-HT1A receptors.

    PubMed

    Espejo-Porras, Francisco; Fernández-Ruiz, Javier; Pertwee, Roger G; Mechoulam, Raphael; García, Concepción

    2013-12-01

    The broad presence of CB1 receptors in the basal ganglia, mainly in GABA- or glutamate-containing neurons, as well as the presence of TRPV1 receptors in dopaminergic neurons and the identification of CB2 receptors in some neuronal subpopulations within the basal ganglia, explain the powerful motor effects exerted by those cannabinoids that can activate/block these receptors. By contrast, cannabidiol (CBD), a phytocannabinoid with a broad therapeutic profile, is generally presented as an example of a cannabinoid compound with no motor effects due to its poor affinity for the CB1 and the CB2 receptor, despite its activity at the TRPV1 receptor. However, recent evidence suggests that CBD may interact with the serotonin 5-HT1A receptor to produce some of its beneficial effects. This may enable CBD to directly influence motor activity through the well-demonstrated role of serotonergic transmission in the basal ganglia. We have investigated this issue in rats using three different pharmacological and neurochemical approaches. First, we compared the motor effects of various i.p. doses of CBD with the selective 5-HT1A receptor agonist, 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT; i.p.). Second, we investigated whether the motor effects of CBD are sensitive to 5-HT1A receptor blockade in comparison with CB1 receptor antagonism. Finally, we investigated whether CBD was able to potentiate the effect of a sub-effective dose of 8-OH-DPAT. Our results demonstrated that: (i) only high doses of CBD (>10 mg/kg) altered motor behavior measured in a computer-aided actimeter; (ii) these alterations were restricted to vertical activity (rearing) with only modest changes in other parameters; (iii) similar effects were produced by 8-OH-DPAT (1 mg/kg), although this agonist affected exclusively vertical activity, with no effects on other motor parameters, and it showed always more potency than CBD; (iv) the effects of 8-OH-DPAT (1 mg/kg) and CBD (20 mg/kg) on vertical activity

  1. Cloning, expression and pharmacology of a truncated splice variant of the human 5-HT7 receptor (h5-HT7(b))

    PubMed Central

    Jasper, J R; Kosaka, A; To, Z P; Chang, D J; Eglen, R M

    1997-01-01

    The rat 5-hydroxytryptamine (5-HT)7 receptor displays two splice variations, a long form, and a truncated splice isoform, arising from the introduction of a stop codon near the carboxy-terminus. The human 5-HT7 receptor gene contains at least two introns and encodes a 445 amino acid 5-HT receptor. A truncated splice variation in the human 5-HT7 receptor was isolated from a human placental cDNA library. In accordance with current NC-IUPHAR nomenclature guidelines, it is suggested that this receptor be denoted as the h5-HT7(b) receptor and the long form of the receptor as h5-HT7(a). The h5-HT7(b) receptor was stably expressed in HEK 293 cells and ligand affinities were determined by displacement of [3H]-5-carboxyamidotryptamine (5-CT; Kd=0.28±0.06 nM, Bmax=7.3±1.7 pmol mg−1 protein). The rank order of affinities (pKi) for a series of ligands was: 5-carboxamidotryptamine (5-CT, 9.65)>5-hydroxytryptamine (5-HT, 9.41)>methiothepin (8.87)>mesulergine (7.87)>8-hydroxy-2(di-n-propylamino)tetralin (8-OH-DPAT, 6.85)>ketanserin (6.44). The h5-HT7(b) receptor coupled positively to adenylyl cyclase in HEK 293 cells. This response was elicited by a number of agonists with the following order of potency (pEC50): 5-CT (8.7±0.11)>5-MeOT (5-methoxytryptamine; 8.1±0.20)>5-HT (7.5±0.13)>tryptamine (5.6±0.36)>8-OH-DPAT (5.3±0.28)>5-methoxytryptamine (5.0±0.06). This rank order was comparable to that observed in the radioligand binding studies. In a similar fashion to that described for the 5-HT7(a) receptor, PCR studies suggested that the 5-HT7(b) receptor mRNA is found in great abundance throughout the brain, in the small intestine and aorta. It is concluded that the h5-HT7 receptor, like the rat receptor, exists as splice variants exhibiting similar pharmacology, signal transduction and distribution. It is thus likely that there exists a complex physiological role for alternate splicing products of the 5-HT7 receptor gene. PMID:9298538

  2. Functional expression of the serotonin 5-HT7 receptor in human glioblastoma cell lines

    PubMed Central

    Mahé, Cécile; Bernhard, Michel; Bobirnac, Ionel; Keser, Corinna; Loetscher, Erika; Feuerbach, Dominik; Dev, Kumlesh K; Schoeffter, Philippe

    2004-01-01

    Serotonin 5-HT7 receptors are present in astrocytes. Understanding their role in this type of cell would greatly benefit from the identification of astroglial cell lines expressing this receptor type. The aim of the present study was to assess the expression of native 5-HT7 receptors and 5-HT7 receptor mRNA in a number of human glioblastoma cell lines, by means of cAMP measurements, Western blot analysis and reverse transcriptase–polymerase chain reaction (RT–PCR) analysis. 5-Hydroxytryptamine (5-HT), 5-carboxamidotryptamine (5-CT), 5-methoxytryptamine (5-MeOT) and 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) induced concentration-dependent stimulations of cAMP accumulation in the human glioblastoma cell lines, U-373 MG, U-138 MG, U-87 MG, DBTRG-05MG, T98G, H4, CCF-STTG1 and Hs 683. The rank order of potency was 5-CT>5-HT=5-MeOT≫8-OH-DPAT. The effect of 5-CT was inhibited in a concentration-dependent manner by the selective 5-HT7 receptor antagonist SB-269970 in all human glioblastoma cells. Schild analyses yielded slope factors close to unity (0.89–1.13) and pA2 values of 8.69–9.05. Western blot analysis revealed the presence of immunoreactive bands corresponding to the human 5-HT7 receptor in extracts of all human glioblastoma cell lines. The presence of the three splice variants of the 5-HT7 receptor (5-HT7(a/b/d)) was visualized by RT–PCR analysis with specific primers in all human glioblastoma cell lines. In conclusion, human glioblastoma cell lines express functional 5-HT7 receptors and the three splice variants of the corresponding mRNA. These cell lines could serve as model systems of native 5-HT7 receptors in glial cells to investigate their putative role in processes like release of neurotrophic factors or inflammatory cytokines. PMID:15339860

  3. Activation of 5-HT1A receptors in the rat dorsomedial hypothalamus inhibits stress-induced activation of the hypothalamic-pituitary-adrenal axis.

    PubMed

    Stamper, Christopher E; Hassell, James E; Kapitz, Adam J; Renner, Kenneth J; Orchinik, Miles; Lowry, Christopher A

    2017-03-27

    Acute activation of the hypothalamic-pituitary-adrenal (HPA) axis, leading to the release of corticosteroid hormones into the circulation, is an adaptive response to perceived threats. Persistent activation of the HPA axis can lead to impaired physiological or behavioral function with maladaptive consequences. Thus, efficient control and termination of stress responses is essential for well-being. However, inhibitory control mechanisms governing the HPA axis are poorly understood. Previous studies suggest that serotonergic systems, acting within the medial hypothalamus, play an important role in inhibitory control of stress-induced HPA axis activity. To test this hypothesis, we surgically implanted chronic jugular cannulae in adult male rats and conducted bilateral microinjection of vehicle or the 5-HT1A receptor agonist, 8-hydroxy-2-(di-n-propylamino) tetralin hydrobromide (8-OH-DPAT; 8 nmol, 0.2 μL, 0.1 μL/min, per side) into the dorsomedial hypothalamus (DMH) immediately prior to a 40 min period of restraint stress. Repeated blood sampling was conducted using an automated blood sampling system and plasma corticosterone concentrations were determined using enzyme-linked immunosorbent assay. Bilateral intra-DMH microinjections of 8-OH-DPAT suppressed stress-induced increases in plasma corticosterone within 10 min of the onset of handling prior to restraint and, as measured by area-under-the-curve analysis of plasma corticosterone concentrations, during the 40 min period of restraint. These data support an inhibitory role for serotonergic systems, acting within the DMH, on stress-induced activation of the HPA axis. Lay summary: Inhibitory control of the hypothalamic-pituitary-adrenal (HPA) stress hormone response is important for well-being. One neurochemical implicated in inhibitory control of the HPA axis is serotonin. In this study we show that activation of serotonin receptors, specifically inhibitory 5-HT1A receptors in the dorsomedial

  4. Similar anxiolytic effects of agonists targeting serotonin 5-HT1A or cannabinoid CB receptors on zebrafish behavior in novel environments

    PubMed Central

    Connors, Kristin A.; Valenti, Theodore W.; Lawless, Kelly; Sackerman, James; Onaivi, Emmanuel S.; Brooks, Bryan W.; Gould, Georgianna G.

    2014-01-01

    The discovery that selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine are present and bioaccumulate in aquatic ecosystems have spurred studies of fish serotonin transporters (SERTs) and changes in SSRI-sensitive behaviors as adverse outcomes relevant for risk assessment. Many SSRIs also act at serotonin 5-HT1A receptors. Since capitolizing on this action may improve treatments of clinical depression and other psychiatric disorders, novel multimodal drugs that agonize 5-HT1A and block SERT were introduced. In mammals both 5-HT1A and CB agonists, such as buspirone and WIN55,212-2, reduce anxious behaviors. Immunological and behavioral evidence suggests that 5-HT1A-like receptors may function similarly in zebrafish (Danio rerio), yet their pharmacological properties are not well characterized. Herein we compared the density of [3H] 8-hydroxy-2-di-n-propylamino tetralin (8-OH-DPAT) binding to 5-HT1A-like sites in the zebrafish brain, to that of simalarly Gαi/o-coupled cannabinoid receptors. [3H] 8-OH-DPAT specific binding was 176 ± 8, 275 ± 32, and 230 ± 36 fmol/mg protein in the hypothalamus, optic tectum, and telencephalon. [3H] WIN55,212-2 binding density was higher in those same brain regions at 6 ± 0.3, 5.5 ± 0.4 and 7.3 ± 0.3 pm/mg protein. The aquatic light-dark plus maze was used to examine behavioral effects of 5-HT1A and CB receptor agonists on zebrafish novelty-based anxiety. With acute exposure to the 5-HT1A partial-agonist buspirone (50 mg/L), or dietary exposure to WIN55,212-2 (7 μg/week) zebrafish spent more time in and/or entered white arms more often than controls (p < 0.05). Acute exposure to WIN55,212-2 at 0.5-50 mg/L, reduced mobility. These behavioral findings suggest that azipirones, like cannabinoid agonists, have anxiolytic and/or sedative properties on fish in novel environments. These observations highlight the need to consider potential ecological risks of azapirones and multimodal antidepressants in the future. PMID

  5. Cloned human 5-HT1A receptor pharmacology determined using agonist binding and measurement of cAMP accumulation.

    PubMed

    Sharif, Najam A; Drace, Colene D; Williams, Gary W; Crider, Julie Y

    2004-10-01

    Twenty agonists and nine antagonists were evaluated for their ability to compete for [3H]-8-hydroxy-2-(di-n-propylamino)tetralin ([3H]-8-OH-DPAT) binding to the cloned human serotonin-1A (ch-5-HT1A) receptor expressed in Chinese hamster ovary cells and for their ability to alter adenylyl cyclase activity in the same cells. The most potent full agonists of high affinity included N,N-dipropyl-5-carboxamidotryptamine (pEC50=9.6 +/- 0.1), MDL 73005EF (pEC50=9.3 +/- 0.2), 5-methyl-urapidil (pEC50=9.2 +/- 0.1), 5-carboxamidotryptamine (pEC50=9.1 +/- 0.2), R(+)-8-OH-DPAT (pEC50=8.6 +/- 0.1) and BMY-7378 (pEC50=8.6 +/- 0.1). WB-4101 (pEC50=8.3 +/- 0.2; IA=79%), clozapine (pEC50=8.1 +/- 0.3; IA=29%), (buspirone (pEC50=7.6 +/- 0.2; IA=79%), quipazine (pEC50 <5; IA=45%) and R-DOI (pEC50 < 5; IA=31%) were weaker agonists with partial agonist properties. The most potent antagonists were WAY-100,635 (pKi=10.2 +/- 0.1), methiothepin (pKi=8.8 +/- 0.2), spiperone (pKi=8.7 +/- 0.2) and NAN-190 (pKi=8.5 +/- 0.2). The receptor affinities and functional potencies were well correlated (r=0.88; P <0.0001). Our binding data correlated well with the pharmacology of endogenous 5-HT1A receptors in the rabbit iris-ciliary body (r=0.91; P <0.001) and rat hippocampus (r=0.93, P <0.0001). Our functional cAMP data correlated well with other cAMP accumulation data (r=0.8, P <0.01 vs calf hippocampus) but less so with [35S]-GTPgammaS binding to the ch-5-HT(1A) receptor as a functional activity read-out (r=0.58, P <0.05). The present study provides a detailed pharmacological characterization of the ch-5-HT1A receptor using binding and functional assays.

  6. Sustained desensitization of hypothalamic 5-Hydroxytryptamine1A receptors after discontinuation of fluoxetine: inhibited neuroendocrine responses to 8-hydroxy-2-(Dipropylamino)Tetralin in the absence of changes in Gi/o/z proteins.

    PubMed

    Raap, D K; Garcia, F; Muma, N A; Wolf, W A; Battaglia, G; van de Kar, L D

    1999-02-01

    Long-term exposure to fluoxetine produces a desensitization of hypothalamic postsynaptic 5-hydroxytryptamine (5-HT)1A receptors, indicated by a substantial inhibition of the 5-HT1A receptor-mediated stimulation of oxytocin and adrenocorticotropic hormone (ACTH) secretion. The present study investigated the time course and mechanism of this desensitization after discontinuation of fluoxetine administration. Male rats were injected with saline or fluoxetine (10 mg/kg/day, i.p.) for 14 days and were challenged with a 5-HT1A agonist, [8-hydroxy-2-(dipropylamino)tetralin (8-OH-DPAT) 50 microg/kg, s.c.] 2, 4, 7, 14, 28, or 60 days post-treatment. In control animals, 8-OH-DPAT significantly increased (approximately 15-fold) plasma levels of oxytocin and ACTH. At 2 days post-treatment, oxytocin and ACTH responses to 8-OH-DPAT were reduced by 74% and 68%, respectively. During further withdrawal from fluoxetine, there was a gradual increase in the oxytocin response toward control levels. However, even 60 days after discontinuation of fluoxetine, the oxytocin response was still significantly reduced by 26% compared with controls. In contrast, the suppressed ACTH response to 8-OH-DPAT (a less-sensitive indicator of desensitization) gradually returned to control levels by day 14 of withdrawal from fluoxetine. Interestingly, the sustained reductions in the hormone responses occurred in the absence of reductions in Gz or Gi protein levels in the hypothalamus. Furthermore, this desensitization was sustained in the absence of detectable levels of fluoxetine and norfluoxetine in plasma and brain tissue. These findings suggest that the sustained desensitization of hypothalamic 5-HT1A receptor systems, observed during fluoxetine withdrawal, may be due to altered interactions among the protein components of the 5-HT1A receptor system, rather than their absolute levels.

  7. Distinct Contributions of Median Raphe Nucleus to Contextual Fear Conditioning and Fear-Potentiated Startle

    PubMed Central

    Silva, R. C. B.; Cruz, A. P. M.; Avanzi, V.; Landeira-Fernandez, J.; Brandão, M. L.

    2002-01-01

    Ascending 5-HT projections from the median raphe nucleus (MRN), probably to the hippocampus, are implicated in the acquisition of contextual fear (background stimuli), as assessed by freezing behavior. Foreground cues like light, used as a conditioned stimulus (CS) in classical fear conditioning, also cause freezing through thalamic transmission to the amygdala. As the MRN projects to the hippocampus and amygdala, the role of this raphe nucleus in fear conditioning to explicit cues remains to be explained. Here we analyzed the behavior of rats with MRN electrolytic lesions in a contextual conditioning situation and in a fear-potentiated startle procedure. The animals received MRN electrolytic lesions either before or on the day after two consecutive training sessions in which they were submitted to 10 conditioning trials, each in an experimental chamber (same context) where they. received foot-shocks (0.6 mA, 1 sec) paired to a 4-sec light CS. Seven to ten days later, the animals were submitted to testing sessions for assessing conditioned fear when they were placed for five shocks, and the duration of contextual freezing was recorded. The animals were then submitted to a fear-potentiated startle in response to a 4-sec light-CS, followed by white noise (100 dB, 50 ms). Control rats (sham) tested in the same context showed more freezing than did rats with pre- or post-training MRN lesions. Startle was clearly potentiated in the presence of light CS in the sham-lesioned animals. Whereas pretraining lesions reduced both freezing and fear-potentiated startle, the post-training lesions reduced only freezing to context, without changing the fear-potentiated startle. In a second experiment, neurotoxic lesions of the MRN with local injections of N-methyl-D-aspartate or the activation of 5-HT1A somatodendritic auto-receptors of the MRN by microinjections of the 5-HT1A receptor agonist 8-hydroxy- 2-(di-n-propylamino)tetralin (8-OH-DPAT) before the training sessions also

  8. Centrally acting hypotensive agents with affinity for 5-HT1A binding sites inhibit forskolin-stimulated adenylate cyclase activity in calf hippocampus.

    PubMed Central

    Schoeffter, P.; Hoyer, D.

    1988-01-01

    1. A number of centrally acting hypotensive agents and other ligands with high affinity for 5-hydroxytryptamine1A (5-HT1A) recognition sites have been tested on forskolin-stimulated adenylate cyclase activity in calf hippocampus, a functional model for 5-HT1A-receptors. 2. Concentration-dependent inhibition of forskolin-stimulated adenylate cyclase activity was elicited by the reference 5-HT1-receptor agonists (mean EC50 value, nM): 5-HT (22), 5-carboxamidotryptamine (5-CT, 3.2), 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT, 8.6), N,N-dipropyl-5-carboxamidotryptamine (DP-5-CT, 2.3), 1-[2-(4-aminophenyl)ethyl]-4-(3-trifluoromethylphenyl)-piperazine (PAPP or LY 165163, 20), 5-methoxy-3-(1,2,3,6-tetrahydro-4-pyridinyl)-1H indole (RU 24969, 20), buspirone (65) and ipsapirone (56). Emax amounted to 18-20% inhibition for all but the latter two agonists (14%). 3. The following hypotensive agents with high affinity for 5-HT1A sites were potent agonists in this system (mean EC50 value, nM): flesinoxan (24), indorenate (99), erythro-1-(1-[2-(1,4-benzodioxan-2-yl)-2-hydroxyethyl]-4-piperidyl )- 2-benzimidazolinone (R 28935, 2.5), urapidil (390) and 5-methyl-urapidil (3.5). The first two agents were full agonists, whereas the latter three acted as partial agonists with 60-80% efficacy. 4. Metergoline and methysergide behaved as full agonists and cyanopindolol as a partial agonist with low efficacy. Spiroxatrine and 2-(2,6-dimethoxyphenoxyethyl)aminomethyl- 1,4-benzodioxane (WB 4101) which bind to 5-HT1A sites with nanomolar affinity, were agonists and inhibited potently forskolin-stimulated adenylate cyclase in calf hippocampus, showing mean EC50 values of 23 and 15 nM, respectively. Spiroxatrine and WB 4101 yielded 90% and 50% efficacy, respectively. 5. Spiperone and methiothepin (each 1 microM) caused rightward shifts of the concentration-effect curve to 8-OH-DPAT, without loss of the maximal effect, as did the partial agonist cyanopindolol (0.1 microM) and the

  9. (R)-(-)-10-methyl-11-hydroxyaporphine: a highly selective serotonergic agonist.

    PubMed

    Cannon, J G; Mohan, P; Bojarski, J; Long, J P; Bhatnagar, R K; Leonard, P A; Flynn, J R; Chatterjee, T K

    1988-02-01

    Prior work in these laboratories identified (+/-)-5-hydroxy-6-methyl-2- (di-n-propylamino)tetralin as a dopaminergic agonist prodrug. The ortho methyl hydroxy aromatic substitution pattern in this molecule has now been incorporated into the aporphine ring system to give a congener of the dopaminergic agonist apomorphine in which the position 10 OH group has been replaced by methyl. Preparation of the target compound involved acid-catalyzed rearrangement of the 3-(1-phenyltetrazolyl) ether of morphine and subsequent molecular modification of the product, the 10-(1-phenyltetrazolyl) ether of (R)-(-)-apomorphine. Surprisingly, the target compound elicited no responses in any assays for effects at dopamine receptors, but rather it displayed pharmacological properties consistent with its being a serotonergic agonist with a high degree of selectivity for 5-HT1A receptors similar to the serotonergic agonist 8-hydroxy-2-(di-n-propylamino)tetralin.

  10. Antidepressant-like effect of 17beta-estradiol: involvement of dopaminergic, serotonergic, and (or) sigma-1 receptor systems.

    PubMed

    Dhir, Ashish; Kulkarni, S K

    2008-10-01

    -1 receptor antagonist), or BD 1047 (1 mg/kg, i.p.; a novel sigma-1 receptor antagonist) reversed the antiimmobility effects of 17beta-estradiol (20 microg/kg, i.p.). Similarly, in mice pretreated with a subthreshold dose of 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT, a 5-HT1A serotonin receptor agonist), 17beta-estradiol (5 microg/kg, i.p.) produced an antidepressant-like effect. These findings demonstrate that 17beta-estradiol exerted an antidepressant-like effect preferentially through the modulation of dopaminergic and serotonergic receptors. This action may also involve the participation of sigma-1 receptors.

  11. The metabolism of tetralin

    PubMed Central

    Elliott, T. H.; Hanam, J.

    1968-01-01

    1. [1-14C]Tetralin was synthesized and fed to rabbits. 2. Of the radioactivity, 87–90% was excreted in the urine within two days and 0·5–3·7% on the third day. The faeces contained 0·6–1·8%. No radioactivity was found in the breath and negligible amounts were retained in the tissues. About 90–99% of an administered dose was accounted for. 3. The main metabolite in the urine was the glucuronide of α-tetralol (52·4%). Other conjugated metabolites were β-tetralol (25·3%), 4-hydroxy-α-tetralone (6·1%), cis-tetralin-1,2-diol (0·4%) and trans-tetralin-1,2-diol (0·6%). 4. β-Tetralone, α-naphthol, 1,2-dihydronaphthalene and naphthalene, previously reported as metabolites, are artifacts, and tetralin, α-tetralone, β-naphthol, 5-hydroxytetralin, and 6-hydroxytetralin are not metabolites. 5. The major metabolite of tetralin, α-tetralol and α-tetralone is the glucuronide of α-tetralol, which was isolated as methyl (1,2,3,4-tetrahydro-1-naphthyl tri-O-acetyl-β-d-glucosid)uronate; the major metabolite of β-tetralol and β-tetralone is the glucuronide of β-tetralol, which was characterized as methyl (1,2,3,4-tetrahydro-2-naphthyl tri-O-acetyl-β-d-glucosid)uronate. 5-Hydroxytetralin is conjugated with glucuronic acid, and was characterized as methyl (5,6,7,8-tetrahydro-1-naphthyl tri-O-acetyl-β-d-glucosid)uronate. 6-Hydroxytetralin is conjugated with glucuronic acid, and was characterized as methyl (5,6,7,8-tetrahydro-2-naphthyl tri-O-acetyl-β-d-glucosid)uronate. 6. A metabolic sequence accounting for the observed biological transformation products is proposed. PMID:4875412

  12. 5HT1A receptor agonist differentially increases cyclic AMP concentration in intact and lesioned goldfish retina. In vitro inhibition of outgrowth by forskolin.

    PubMed

    Urbina, M; Schmeer, C; Lima, L

    1996-11-01

    5HT1A receptors occur in the retina of various species and the administration of 5HT1A agonists results in the inhibition of outgrowth from postcrush goldfish retinal explants. The levels of cyclic AMP (cAMP) play a role in the modulation of the outgrowth of the nevous system. Moreover, the stimulation of central 5HT1A receptors with the agonist 8-hydroxy-2-(di-n-propylamino)tetralin has been reported to produce an increase or decrease in the activity of adenylate cyclase. In the present investigation we studied the effect of adenylate cyclase stimulation by forskolin, as well as the modulatory effects of 5HT1A receptor agonists and antagonists on the production of cAMP in the goldfish retina, and on the outgrowth of this tissue in vitro. 8-Hydroxy-2-(di-n-propylamino)tetralin produced a significant and dose-dependent increase in cAMP concentration. This effect was not additive to the stimulation produced by forskolin. By contrast, as previously described, the 5HT1A agonist decreased cAMP concentration in the hippocampus of the rat. Both effects were significantly impaired by the 5HT1A antagonist WAY-100,135. A significant effect of the antagonist alone was observed only in the goldfish retina. The increase in cAMP levels was greater in the intact than in the postcrush retina. In addition, forskolin decreased the outgrowth of postcrush retinal explants in a dose-dependent manner, suggesting the importance of critical levels of cAMP in this process. Taken together, 5HT1A receptors seem to be positively coupled to adenylate cyclase in the goldfish retina, where cAMP plays a role as a modulator of outgrowth and regeneration. The inhibitory effect of 5HT1A receptor agonists on retinal outgrowth might be mediated through the production of cAMP. The activation of other subtypes of 5HT receptors positively coupled to adenylate cyclase by the 5HT1A agonist, such as 5HT7, cannot be discarded.

  13. Serotonergic modulation of hippocampal pyramidal cells in euthermic, cold-acclimated, and hibernating hamsters

    NASA Technical Reports Server (NTRS)

    Horrigan, D. J.; Horwitz, B. A.; Horowitz, J. M.

    1997-01-01

    Serotonergic fibers project to the hippocampus, a brain area previously shown to have distinctive changes in electroencephalograph (EEG) activity during entrance into and arousal from hibernation. The EEG activity is generated by pyramidal cells in both hibernating and nonhibernating species. Using the brain slice preparation, we characterized serotonergic responses of these CA1 pyramidal cells in euthermic, cold-acclimated, and hibernating Syrian hamsters. Stimulation of Shaffer-collateral/commissural fibers evoked fast synaptic excitation of CA1 pyramidal cells, a response monitored by recording population spikes (the synchronous generation of action potentials). Neuromodulation by serotonin (5-HT) decreased population spike amplitude by 54% in cold-acclimated animals, 80% in hibernating hamsters, and 63% in euthermic animals. The depression was significantly greater in slices from hibernators than from cold-acclimated animals. In slices from euthermic animals, changes in extracellular K+ concentration between 2.5 and 5.0 mM did not significantly alter serotonergic responses. The 5-HT1A agonist 8-hydroxy-2(di-n-propylamino)tetralin mimicked serotonergic inhibition in euthermic hamsters. Results show that 5-HT is a robust neuromodulator not only in euthermic animals but also in cold-acclimated and hibernating hamsters.

  14. Photoaffinity labeling of the 5-hydroxytryptamine 1A receptor in rat hippocampus.

    PubMed

    Ransom, R W; Asarch, K B; Shih, J C

    1986-10-01

    1-[2-(4-Azidophenyl)ethyl]-4-(3-trifluoromethylphenyl)piperazine (p-azido-PAPP) inhibits [3H]5-hydroxytryptamine [( 3H]5-HT) binding to 5-HT1A and 5-HT1B sites in rat brain with equilibrium dissociation constants (KD) of 0.9 nM and 230 nM, respectively. [3H]p-Azido-PAPP was synthesized and its reversible and irreversible binding properties to the hippocampal 5-HT1A site characterized. [3H]p-Azido-PAPP labeled a single class of sites in rat hippocampal membranes with a KD of 1 nM and a maximal binding density of 370 fmol/mg protein. The pharmacological profile of [3H]p-azido-PAPP binding was consistent with the radioligand's selective interaction with the 5-HT1A receptor. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of membranes preincubated with [3H]p-azido-PAPP and irradiated showed a major band of incorporation of radioactivity at approximately 55,000 daltons. This incorporation could be blocked when membranes were incubated with 1 microM of several agents that have high affinity for 5-HT1A sites [5-HT, 8-hydroxy-2-(di-n-propylamino)tetraline, TVX Q 7821, spiperone, buspirone, d-lysergic acid diethylamide, metergoline]. The results indicate that on photolysis [3H]p-azido-PAPP irreversibly labels a polypeptide that is, or is a subunit of, the 5-HT1A receptor in rat hippocampus.

  15. The Autoignition of Tetralin, an Endothermic Fuel

    NASA Astrophysics Data System (ADS)

    Gerken, William James

    The history of the evolution of jet fuel, starting with JP-1 in the early 1950s and resulting in JP-8-100 is presented. The importance of fuel properties from a perspective of balancing availability, cost, and performance is illustrated with insight from the XB-70, SR-71, and U-2. Current jet fuel advancements are discussed, and found to revolve around the need for increased heat capacity for high speed aircraft. Benefits of increased thermal management, such as reduced emissions, engine weight, and increased performance are also discussed. Endothermic fuels, which undergo controlled pyrolysis at high temperatures reduce the formation of coke through hydrogen donation, and absorb energy in their pyrolysis reaction. Due to the potential applications of tetralin, an endothermic hydrocarbon, as an additive or fuel to increase the capacity of aircraft fuels to absorb energy, the ignition delay characteristics of tetralin are experimentally investigated and compared with other fuels containing aromatic and naphthenic functionalities. Future work should focus on developing a kinetic model to describe tetralin oxidation and ignition for use in combustion simulations.

  16. Activation of dorsal raphe serotonin neurons is necessary for waiting for delayed rewards.

    PubMed

    Miyazaki, Kayoko W; Miyazaki, Katsuhiko; Doya, Kenji

    2012-08-01

    The forebrain serotonergic system is a crucial component in the control of impulsive behaviors. We previously reported that the activity of serotonin neurons in the midbrain dorsal raphe nucleus increased when rats performed a task that required them to wait for delayed rewards. However, the causal relationship between serotonin neural activity and the tolerance for the delayed reward remained unclear. Here, we test whether the inhibition of serotonin neural activity by the local application of the 5-HT(1A) receptor agonist 8-hydroxy-2-(di-n-propylamino) tetralin in the dorsal raphe nucleus impairs rats' tolerance for delayed rewards. Rats performed a sequential food-water navigation task that required them to visit food and water sites alternately via a tone site to get rewards at both sites after delays. During the short (2 s) delayed reward condition, the inhibition of serotonin neural activity did not significantly influence the numbers of reward choice errors (nosepoke at an incorrect reward site following a conditioned reinforcer tone), reward wait errors (failure to wait for the delayed rewards), or total trials (sum of reward choice errors, reward wait errors, and acquired rewards). By contrast, during the long (7-11 s) delayed reward condition, the number of wait errors significantly increased while the numbers of total trials and choice errors did not significantly change. These results indicate that the activation of dorsal raphe serotonin neurons is necessary for waiting for long delayed rewards and suggest that elevated serotonin activity facilitates waiting behavior when there is the prospect of forthcoming rewards.

  17. Low nanomolar serotonin inhibits the glutamate receptor/nitric oxide/cyclic GMP pathway in slices from adult rat cerebellum.

    PubMed

    Maura, G; Guadagnin, A; Raiteri, M

    1995-09-01

    The function of serotonin afferents to the cerebellum has been investigated by monitoring the effects of serotoninergic drugs on the production of cyclic GMP elicited in cerebellar slices by activation of ionotropic glutamate receptors. Exposure of adult rat cerebellar slices to N-methyl-D-aspartate (1 nM to 1 microM) or to (RS)-alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA; 1 nM to 10 microM) elicited concentration-dependent and saturable rises in the levels of cyclic GMP. These responses were blocked by selective antagonists at the N-methyl-D-aspartate or AMPA receptors and by inhibiting nitric oxide synthase, but were insensitive to tetrodotoxin. When tested between 0.1 and 10 nM, serotonin, the serotonin1A receptor agonist (+/-)-8-hydroxy-2-(di-n-propylamino)tetralin and the serotonin2 receptor agonist (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane inhibited, concentration-dependently, the cyclic GMP responses evoked by near-maximal (0.1 microM) concentrations of N-methyl-D-aspartate or AMPA. The EC50 values (concentrations causing half-maximal effect) ranged between 0.7 and 2.1 nM. The actions of serotonin were totally abolished by methiothepin, a mixed-type serotonin receptor antagonist. Thus, the serotonergic cerebellar afferents may exert a potent inhibitory control on the excitatory transmission mediated by N-methyl-D-aspartate and AMPA receptors; the inhibition occurs through both serotonin1A and serotonin2 receptors. As the glutamate receptor-dependent cyclic GMP responses involve production of nitric oxide, a diffusible activator of guanylate cyclase, the above inhibitory serotonin receptors may have multiple localization.(ABSTRACT TRUNCATED AT 250 WORDS)

  18. The zebra mussel (Dreissena polymorpha), a new pest in North America: reproductive mechanisms as possible targets of control strategies

    USGS Publications Warehouse

    Ram, Jeffrey L.; Fong, Peter; Croll, Roger P.; Nichols, Susan J.; Wall, Darcie

    1992-01-01

    The zebra mussel (Dreissena polymorpha) has spread rapidly in temperate fresh waters of North America since its introduction into the Great Lakes in 1985 or 1986. It attaches to hard substrates, forming layers, occluding water intakes, encrusting and killing native mussels, filtering algae in competition with other planktivores, and possibly interfering with fish spawning. It reproduces prolifically, suggesting that an approach to its control may be by controlling its reproduction. Previous literature suggests that spawning in bivalves is regulated by both environmental and internal chemical cues. A suggested sequence is that phytoplankton chemicals initially trigger spawning; chemicals associated with gametes provide a species-specific pheromonal positive feedback for spawning; and the response to environmental chemicals is mediated internally by serotonin (5-HT). The role of 5-HT in zebra mussels is under investigation. Both males and females can be induced to spawn by either injection or external application of 5-HT. The response can also be activated by 8-hydroxy-2-(di-n-propylamino)-tetralin, an agonist at 5-HT1A receptors. HPLC analysis has detected 5-HT as the major biogenic amine in both male and female gonads. 5-HT immunocytochemistry demonstrates nerves containing serotonergic fibers innervating gonads of both males and females, with prominent varicosities surrounding the follicles in both sexes. A role of 5-HT in mediating spawning responses in zebra mussels is thus strongly supported. These studies have shown that reproductive behavior of zebra mussels can be modified by outside chemicals, a property that may be exploited for purposes of control.

  19. Dual Role of Endogenous Serotonin in 2,4,6-Trinitrobenzene Sulfonic Acid-Induced Colitis

    PubMed Central

    Rapalli, Alberto; Bertoni, Simona; Arcaro, Valentina; Saccani, Francesca; Grandi, Andrea; Vivo, Valentina; Cantoni, Anna M.; Barocelli, Elisabetta

    2016-01-01

    Background and Aims: Changes in gut serotonin (5-HT) content have been described in Inflammatory Bowel Disease (IBD) and in different experimental models of colitis: the critical role of this monoamine in the pathogenesis of chronic gastrointestinal inflammation is gradually emerging. Aim of the present study was to evaluate the contribution of endogenous 5-HT through the activation of its specific receptor subtypes to the local and systemic inflammatory responses in an experimental model of IBD. Materials and Methods: Colitis was induced by intrarectal 2,4,6-TriNitroBenzene Sulfonic acid in mice subacutely treated with selective antagonists of 5-HT1A (WAY100135), 5-HT2A (Ketanserin), 5-HT3 (Ondansetron), 5-HT4 (GR125487), 5-HT7 (SB269970) receptors and with 5-HT1A agonist 8-Hydroxy-2-(di-n-propylamino)tetralin. Results: Blockade of 5-HT1A receptors worsened TNBS-induced local and systemic neutrophil recruitment while 5-HT1A agonist delayed and mitigated the severity of colitis, counteracting the increase in colonic 5-HT content. On the contrary, blockade of 5-HT2A receptors improved global health conditions, reduced colonic morphological alterations, down-regulated neutrophil recruitment, inflammatory cytokines levels and colonic apoptosis. Antagonism of 5-HT3, 5-HT4, and 5-HT7 receptor sites did not remarkably affect the progression and outcome of the pathology or only slightly improved it. Conclusion: The prevailing deleterious contribution given by endogenous 5-HT to inflammation in TNBS-induced colitis is seemingly mediated by 5-HT2A and, to a lesser extent, by 5-HT4 receptors and coexists with the weak beneficial effect elicited by 5-HT1A stimulation. These findings suggest how only a selective interference with 5-HT pro-inflammatory actions may represent an additional potential therapeutic option for intestinal inflammatory disorders. PMID:27047383

  20. Conservation of 5-HT1A receptor-mediated autoinhibition of serotonin (5-HT) neurons in mice with altered 5-HT homeostasis.

    PubMed

    Araragi, Naozumi; Mlinar, Boris; Baccini, Gilda; Gutknecht, Lise; Lesch, Klaus-Peter; Corradetti, Renato

    2013-01-01

    Firing activity of serotonin (5-HT) neurons in the dorsal raphe nucleus (DRN) is controlled by inhibitory somatodendritic 5-HT1A autoreceptors. This autoinhibitory mechanism is implicated in the etiology of disorders of emotion regulation, such as anxiety disorders and depression, as well as in the mechanism of antidepressant action. Here, we investigated how persistent alterations in brain 5-HT availability affect autoinhibition in two genetically modified mouse models lacking critical mediators of serotonergic transmission: 5-HT transporter knockout (Sert-/-) and tryptophan hydroxylase-2 knockout (Tph2-/-) mice. The degree of autoinhibition was assessed by loose-seal cell-attached recording in DRN slices. First, application of the 5-HT1A-selective agonist R(+)-8-hydroxy-2-(di-n-propylamino)tetralin showed mild sensitization and marked desensitization of 5-HT1A receptors in Tph2-/- mice and Sert-/- mice, respectively. While 5-HT neurons from Tph2-/- mice did not display autoinhibition in response to L-tryptophan, autoinhibition of these neurons was unaltered in Sert-/- mice despite marked desensitization of their 5-HT1A autoreceptors. When the Tph2-dependent 5-HT synthesis step was bypassed by application of 5-hydroxy-L-tryptophan (5-HTP), neurons from both Tph2-/- and Sert-/- mice decreased their firing rates at significantly lower concentrations of 5-HTP compared to wildtype controls. Our findings demonstrate that, as opposed to the prevalent view, sensitivity of somatodendritic 5-HT1A receptors does not predict the magnitude of 5-HT neuron autoinhibition. Changes in 5-HT1A receptor sensitivity may rather be seen as an adaptive mechanism to keep autoinhibition functioning in response to extremely altered levels of extracellular 5-HT resulting from targeted inactivation of mediators of serotonergic signaling.

  1. Characterization of midline medulla role in the trigeminal depressor response.

    PubMed

    Clement, M E; McCall, R B

    1989-05-01

    The purpose of the present investigation was to determine the role of the midline medulla in mediating the trigeminal depressor response. Previously we found that lesions of the midline medulla abolished the decrease in blood pressure resulting from electrical stimulation of the spinal trigeminal complex. Electrical stimulation (5 Hz) of the spinal trigeminal tract elicited a decrease in arterial blood pressure that was associated with an inhibition of sympathetic nerve activity recorded from the inferior cardiac nerve of anesthetized cats. The effect of single shocks applied to the trigeminal complex on sympathetic activity was determined using computer-averaging techniques. Single shock stimulation consistently elicited an excitation of sympathetic activity that was followed by an inhibition of sympathetic nerve discharge. The gamma-aminobutyric acid antagonist picrotoxin blocked the depressor response elicited by electrical stimulation of the midline medulla but not by stimulation of the spinal trigeminal complex. Extracellular recordings of the discharges of midline medullary neurons were made to determine the effects of trigeminal stimulation on sympathoinhibitory, sympathoexcitatory, and serotonin neurons. Sympathoinhibitory and sympathoexcitatory neurons were identified by the relationship between unitary discharges and sympathetic nerve activity and by their response to baroreceptor reflex activation. Serotonin (5-HT) neurons were identified using criteria previously developed in our laboratory. These included 1) a slow regular discharge rate, 2) sensitivity to the inhibitory action of the 5-HT1A agonist 8-OH 8-hydroxy-2-(di-n-propylamino)tetralin, 3) failure to respond to baroreceptor reflex activation, and 4) the discharges of the 5-HT neurons were not related to sympathetic activity. Stimulation of the spinal trigeminal complex typically inhibited the discharges of sympathoinhibitory neurons. In contrast, stimulation of the trigeminal complex

  2. Role of 5-HT(1A) and 5-HT(1B) receptors in the antidepressant-like effect of piperine in the forced swim test.

    PubMed

    Mao, Qing-Qiu; Huang, Zhen; Ip, Siu-Po; Xian, Yan-Fang; Che, Chun-Tao

    2011-10-24

    Our previous studies have showed that treating mice with piperine significantly decreased the immobility time of the animals in the forced swim test and tail suspension test, which was related to up-regulation of serotonin (5-HT) level in the brain. The purpose of this study is to explore the contribution of 5-HT receptors in the antidepressant-like effect of piperine. The results showed that pre-treating mice with methiothepin (a non-selective 5-HT receptor antagonist, 0.1mg/kg, intraperitoneally), 4-(2'-methoxy-phenyl)-1-[2'-(n-2″-pyridinyl)-p-iodobenzamino-]ethyl-piperazine (a selective 5-HT(1A) receptor antagonist, 1mg/kg, subcutaneously) or 1-(2-(1-pyrrolyl)-phenoxy)-3-isopropylamino-2-propanol (a 5-HT(1B) receptor antagonist, 2.5mg/kg, intraperitoneally) was found to abolish the anti-immobility effect of piperine (10mg/kg, intraperitoneally) in the forced swim test. On the other hand, a sub-effective dose of piperine (1mg/kg, intraperitoneally) produced a synergistic antidepressant-like effect with (+)-8-hydroxy-2-(di-n-propylamino)tetralin (a 5-HT(1A) receptor agonist, 1mg/kg, intraperitoneally) or anpirtoline (a 5-HT(1B) receptor agonist, 0.25mg/kg, intraperitoneally). Taken together, these results suggest that the antidepressant-like effect of piperine in the mouse forced swim test may be mediated, at least in part, by the activation of 5-HT(1A) and 5-HT(1B) receptors.

  3. Density and viscosity of tetralin and trans-decalin

    NASA Astrophysics Data System (ADS)

    Gonçalves, F. A.; Hamano, K.; Sengers, J. V.

    1989-07-01

    New measurements are reported for the density and viscosity of tetralin and trans-decalin. The density was determined from room temperature to 60°C for tetralin and to 95°C for trans-decalin. The kinematic viscosity was measured up to temperatures slightly above 100°C. Our results improve upon the values recommended by the American Petroleum Institute for these liquids.

  4. Alkaline pretreatment and the synergic effect of water and tetralin enhances the liquefaction efficiency of bagasse.

    PubMed

    Li, Zhixia; Cao, Jiangfei; Huang, Kai; Hong, Yaming; Li, Cunlong; Zhou, Xinxin; Xie, Ning; Lai, Fang; Shen, Fang; Chen, Congjin

    2015-02-01

    Bagasse liquefaction (BL) in water, tetralin, and water/tetralin mixed solvents (WTMS) was investigated, and effects of tetralin content in WTMS, temperature, and alkaline pretreatment of bagasse on liquefaction efficiency were studied. At 300°C, bagasse conversion in WTMS with tetralin content higher than 50 wt% was 86-87 wt%, whereas bagasse conversion in water or tetralin was 67 wt% or 84 wt%, respectively. Because the solid conversion from liquefaction in WTMS with tetralin content higher than 50 wt% was always higher than that in water or tetralin at temperatures between 250 and 300°C, a synergic effect between water and tetralin is suggested. Alkaline pretreatment of bagasse resulted in significantly higher conversion and heavy oil yield from BL in water or WTMS. The effect of deoxygenation by the present liquefaction method is demonstrated by lower oxygen contents (16.01-19.59 wt%) and higher heating values (31.9-34.8 MJ/kg) in the produced oils.

  5. (3H)WB4101 labels the 5-HT1A serotonin receptor subtype in rat brain. Guanine nucleotide and divalent cation sensitivity

    SciTech Connect

    Norman, A.B.; Battaglia, G.; Creese, I.

    1985-12-01

    In the presence of a 30 nM prazosin mask, (/sup 3/H)-2-(2,6-dimethoxyphenoxyethyl) aminomethyl-1,4-benzodioxane ((/sup 3/H)WB4101) can selectively label 5-HT1 serotonin receptors. Serotonin exhibits high affinity (Ki = 2.5 nM) and monophasic competition for (/sup 3/H) WB4101 binding in cerebral cortex. We have found a significant correlation (r = 0.96) between the affinities of a number of serotonergic and nonserotonergic compounds at (/sup 3/H)WB4101-binding sites in the presence of 30 nM prazosin and (/sup 3/H) lysergic acid diethylamide ((/sup 3/H)LSD)-labeled 5-HT1 serotonin receptors in homogenates of rat cerebral cortex. Despite similar pharmacological profiles, distribution studies indicate that, in the presence of 5 mM MgSO4, the Bmax of (/sup 3/H)WB4101 is significantly lower than the Bmax of (/sup 3/H)LSD in various brain regions. WB4101 competition for (/sup 3/H) LSD-labeled 5-HT1 receptors fits best to a computer-derived model assuming two binding sites, with the KH for WB4101 being similar to the KD of (/sup 3/H)WB4101 binding derived from saturation experiments. This suggests that (/sup 3/H)WB4101 labels only one of the subtypes of the 5-HT1 serotonin receptors labeled by (/sup 3/H)LSD. The selective 5-HT1A serotonin receptor antagonist, spiperone, and the selective 5-HT1A agonist, 8-hydroxy-2-(di-n-propylamino) tetraline, exhibit high affinity and monophasic competition for (/sup 3/H)WB4101 but compete for multiple (/sup 3/H)LSD 5-HT1 binding sites. These data indicate that (/sup 3/H)WB4101 selectively labels the 5-HT1A serotonin receptor, whereas (/sup 3/H) LSD appears to label both the 5-HT1A and the 5-HT1B serotonin receptor subtypes. The divalent cations, Mn2+, Mg2+, and Ca2+ were found to markedly increase the affinity and Bmax of (/sup 3/H)WB4101 binding in cerebral cortex. Conversely, the guanine nucleotides guanylylimidodiphosphate and GTP, but not the adenosine nucleotide ATP, markedly reduce the Bmax of (/sup 3/H)WB4101 binding.

  6. Effects of the membrane action of tetralin on the functional and structural properties of artificial and bacterial membranes.

    PubMed Central

    Sikkema, J; Poolman, B; Konings, W N; de Bont, J A

    1992-01-01

    Tetralin is toxic to bacterial cells at concentrations below 100 mumol/liter. To assess the inhibitory action of tetralin on bacterial membranes, a membrane model system, consisting of proteoliposomes in which beef heart cytochrome c oxidase was reconstituted as the proton motive force-generating mechanism, and several gram-positive and gram-negative bacteria were studied. Because of its hydrophobicity, tetralin partitioned into lipid membranes preferentially (lipid/buffer partition coefficient of tetralin is approximately 1,100). The excessive accumulation of tetralin caused expansion of the membrane and impairment of different membrane functions. Studies with proteoliposomes and intact cells indicated that tetralin makes the membrane permeable for ions (protons) and inhibits the respiratory enzymes, which leads to a partial dissipation of the pH gradient and electrical potential. The effect of tetralin on the components of the proton motive force as well as disruption of protein-lipid interaction(s) could lead to impairment of various metabolic functions and to low growth rates. The data offer an explanation for the difficulty in isolating and cultivating microorganisms in media containing tetralin or other lipophilic compounds. PMID:1314806

  7. Quantitative separation of tetralin hydroperoxide from its decomposition products by high performance liquid chromatography

    NASA Technical Reports Server (NTRS)

    Worstell, J. H.; Daniel, S. R.

    1981-01-01

    A method for the separation and analysis of tetralin hydroperoxide and its decomposition products by high pressure liquid chromatography has been developed. Elution with a single, mixed solvent from a micron-Porasil column was employed. Constant response factors (internal standard method) over large concentration ranges and reproducible retention parameters are reported.

  8. Food restriction and streptozotocin differentially modify sensitivity to the hypothermic effects of direct- and indirect-acting serotonin receptor agonists in rats.

    PubMed

    Li, Jun-Xu; Koek, Wouter; France, Charles P

    2009-06-24

    Food restriction and experimentally-induced diabetes (streptozotocin) can modify serotonin (5-HT) neurotransmission and sensitivity to drugs acting on 5-HT systems. This study examined the effects of food restriction and streptozotocin on the hypothermic effects of the 5-HT(1A) receptor agonist (+)-8-hydroxy-2-(dipropylamino)tetralin hydrobromide (8-OH-DPAT), the 5-HT(2) receptor agonist (+/-)-2,5-dimethoxy-4-methylamphetamine hydrochloride (DOM), the 5-HT releaser fenfluramine, and the selective 5-HT reuptake inhibitor (SSRI) fluoxetine. All four drugs significantly decreased body temperature in free feeding rats. Limiting rats to 10 g/day of food for 7 days decreased body weight and sensitivity to 8-OH-DPAT induced hypothermia, without affecting sensitivity to DOM, fenfluramine, or fluoxetine induced hypothermia. Subsequently, 7 days of free feeding restored body weight and sensitivity to 8-OH-DPAT. Sensitivity to all drugs was significantly decreased 7 days after 50 mg/kg streptozotocin; subsequently, 10 days of insulin replacement restored sensitivity to all drugs. These results extend to body temperature the observation that food restriction and experimentally-induced diabetes differentially modify sensitivity to drugs acting on 5-HT systems and they further suggest that the clinical response to therapeutic drugs acting on 5-HT systems might be impacted by nutritional and insulin status.

  9. Effects of 5-HT-receptor and alpha 2-adrenoceptor ligands on the haemodynamic response to acute central hypovolaemia in conscious rabbits.

    PubMed Central

    Evans, R. G.; Haynes, J. M.; Ludbrook, J.

    1993-01-01

    1. We set out to elucidate the pharmacological mechanisms by which alpha 2-adrenoceptor and 5-HT-receptor ligands affect the haemodynamic response to acute central hypovolaemia in conscious rabbits. 2. Acute central hypovolaemia was produced by inflating an inferior vena caval cuff so that cardiac output fell at a constant rate of approximately 8.5% of its baseline level per min. 3. Drugs were administered into the fourth cerebral ventricle in either 154 mM NaCl (saline) or 20% w/v 2-hydroxypropyl-beta-cyclodextrin (beta-CDX). After vehicle treatments, the haemodynamic response to acute central hypovolaemia had the usual two phases. During Phase I, systemic vascular conductance fell in proportion to cardiac output so that mean arterial pressure fell by only 8 mmHg. Phase II commenced when cardiac output had fallen to approximately 60% of its baseline level, when vascular conductance rose abruptly and arterial pressure fell to < or = 40 mmHg. The haemodynamic response was not dependent on the vehicle used (saline or beta-CDX). 4. Methysergide delayed the occurrence of Phase II in a dose-dependent manner, and prevented it at a dose of 30- 600 nmol (geometric mean = 186 nmol). The effects and potency of methysergide were not dependent on the vehicle used, indicating that beta-CDX can be used as a vehicle for fourth ventricular administration of lipophilic drugs to conscious rabbits. Clonidine (10 nmol) reversed the effects of a critical dose of methysergide. 5. Phase II was also prevented by 8-hydroxy-2-(di-n-propylamino)tetralin (5-HT1A-selective agonist, geometric mean critical dose (range) = 13.1 (10-30) nmol), sumatriptan (5-HT1D-selective agonist, 72.1 (10-300) nmol), mesulergine (5-HT2/1C-selective antagonist, 173 (30-1000) nmol), idazoxan (alpha 2-adrenoceptor-selective antagonist, 548 (100-3000) nmol), and mianserin (5-HT2/1C-selective antagonist, 548 (100-3000) nmol). It was not affected by MDL 72222 (5-HT3-selective antagonist, 300 nmol) or ketanserin (5-HT2

  10. Generalized kinetic model of catalyzed hydroliquefaction of coal incorporating tetralin dehydrogenation reaction

    SciTech Connect

    Ghosh, A.K.; Prasad, G.N.; Sridhar, T.

    1987-09-01

    A three-component kinetic model previously reported for uncatalyzed liquefaction has been used to simulate hydroliquefaction of Victorian brown coal with three different types of catalysts: iron-tin; iron; and haematite. The presence of catalyst is found to enhance hydrogenation of coal as well as the equilibrium hydrogenation-dehydrogenation reactions involving donor solvent. The thermal dissolution and autohydrogenation reaction rates are independent of catalyst used. Iron-tin-based catalyst has been found to be most effective for the hydrogenation reaction step. The simulation shows that the reactions producing hydrogen from tetralin are much slower than the coal-hydrogen reactions; hence, efforts aimed at efficient abstraction of hydrogen from the hydrogen donors may be beneficial.

  11. Effect of the particle size of a heterogeneous catalyst on the kinetics of liquid-phase oxidation of tetralin

    SciTech Connect

    Artemov, A.V.; Vainshtein, E.F.

    1988-01-10

    The dependence of the initial rate of oxidation of tetralin on the particle size of the Co/sup 2 +//SiO/sub 2/ catalyst is shown. The method proposed permitted explanation of the dependence of the kinetics of liquid-phase processes in the absence of extra- and intradiffusion hindrances on the particle size of a heterogeneous catalyst and estimation of the values of the kinetic constants from this dependence.

  12. Ab initio study for the hydrogen abstraction reactions on toluene and tetralin.

    SciTech Connect

    Beste, Ariana; Harrison, Robert J; Britt, Phillip F; Buchanan III, A C

    2006-01-01

    Hydrogen abstraction reactions play a key role in many thermal and catalytic processes involved in the production of fuels and chemicals. In this paper, the hydrogen abstraction reactions on toluene and tetralin by the benzyl radical are investigated by ab initio methods. These reactions are representatives of similar reactions occurring in the thermolysis of lignin model compounds containing the phenethyl phenyl ether (PPE) structural moiety. The title reactions serve to calibrate the theoretical methods to be used in the study of PPE pyrolysis through comparison of the reaction barriers with reliable experimental values. We used two different hybrid density functionals (BHandHLYP, B3LYP) and second-order perturbation theory to obtain equilibrium and transition state geometries. We recomputed selected energy barriers at the B3LYP geometries with the coupled cluster singles and doubles (CCSD) method. Multiple transition states were found for both reactions. BHandHLYP underestimates and second-order perturbation theory overestimates the reaction barriers; B3LYP energy barriers agree well with experiment and the corresponding CCSD energy barriers. The flat potential energy surface around the saddle points causes numerical inaccuracies. We observe the break down of the harmonic approximation in the calculation of low frequencies.

  13. Thermal gravitational separation of ternary mixture n-dodecane/isobutylbenzene/tetralin components in a porous medium

    NASA Astrophysics Data System (ADS)

    Larabi, Mohamed Aziz; Mutschler, Dimitri; Mojtabi, Abdelkader

    2016-06-01

    Our present work focuses on the coupling between thermal diffusion and convection in order to improve the thermal gravitational separation of mixture components. The separation phenomenon was studied in a porous medium contained in vertical columns. We performed analytical and numerical simulations to corroborate the experimental measurements of the thermal diffusion coefficients of ternary mixture n-dodecane, isobutylbenzene, and tetralin obtained in microgravity in the international space station. Our approach corroborates the existing data published in the literature. The authors show that it is possible to quantify and to optimize the species separation for ternary mixtures. The authors checked, for ternary mixtures, the validity of the "forgotten effect hypothesis" established for binary mixtures by Furry, Jones, and Onsager. Two complete and different analytical resolution methods were used in order to describe the separation in terms of Lewis numbers, the separation ratios, the cross-diffusion coefficients, and the Rayleigh number. The analytical model is based on the parallel flow approximation. In order to validate this model, a numerical simulation was performed using the finite element method. From our new approach to vertical separation columns, new relations for mass fraction gradients and the optimal Rayleigh number for each component of the ternary mixture were obtained.

  14. Ab initio study of the kinetics of hydrogen abstraction reactions on toluene and tetralin

    SciTech Connect

    Beste, Ariana; Britt, Phillip F; Buchanan III, A C; Harrison, Robert J; Hathorn, Bryan C

    2008-01-01

    Hydrogen abstraction reactions play a key role in many thermal and catalytic processes involved in the production of fuels and chemicals. In this paper, the reaction barriers and rate constants for the hydrogen abstraction reactions on toluene and tetralin by the benzyl radical are calculated by ab initio methods. These reactions are representatives of similar reactions occurring in the thermolysis of lignin model compounds containing the phenethyl phenyl ether (PPE) structural moiety. Thermolysis of PPE occurs by a free radical chain mechanism in which the product selectivity arises from competitive hydrogen abstraction at the benzylic and nonbenzylic methylen sites by chain carrying benzyl and phenoxyl radicals. The title reactions serve to calibrate the theoretical methods to be used in the study of PPE through comparison of the rate constants and the reaction enthalpies with reliable experimental values. In this study, we used two different hybrid density functionals (BHandHLYP, B3LYP) and second-order perturbation theory to obtain equilibrium and transition state geometries. Multiple transition states were found for both reactions. BHandHLYP underestimates and second-order perturbation theory overestimates the reaction barriers; B3LYP energy barriers agree well with experiment. Absolute and relative rate constants were calculated using transition state theory. We found that the relative rate constant using the B3LYP functional agrees within a factor of 2.0 with experiment at the experimental temperature of 333 K, indicating that the B3LYP functional will be successful in predicting relative rate constants for hydrogen abstraction reactions participating in the pyrolysis of PPE.

  15. Redox proteins of hydroxylating bacterial dioxygenases establish a regulatory cascade that prevents gratuitous induction of tetralin biodegradation genes.

    PubMed

    Ledesma-García, Laura; Sánchez-Azqueta, Ana; Medina, Milagros; Reyes-Ramírez, Francisca; Santero, Eduardo

    2016-03-31

    Bacterial dioxygenase systems are multicomponent enzymes that catalyze the initial degradation of many environmentally hazardous compounds. In Sphingopyxis granuli strain TFA tetralin dioxygenase hydroxylates tetralin, an organic contaminant. It consists of a ferredoxin reductase (ThnA4), a ferredoxin (ThnA3) and a oxygenase (ThnA1/ThnA2), forming a NAD(P)H-ThnA4-ThnA3-ThnA1/ThnA2 electron transport chain. ThnA3 has also a regulatory function since it prevents expression of tetralin degradation genes (thn) in the presence of non-metabolizable substrates of the catabolic pathway. This role is of physiological relevance since avoids gratuitous and wasteful production of catabolic enzymes. Our hypothesis for thn regulation implies that ThnA3 exerts its action by diverting electrons towards the regulator ThnY, an iron-sulfur flavoprotein that together with the transcriptional activator ThnR is necessary for thn gene expression. Here we analyze electron transfer among ThnA4, ThnA3 and ThnY by using stopped-flow spectrophotometry and determination of midpoint reduction potentials. Our results indicate that when accumulated in its reduced form ThnA3 is able to fully reduce ThnY. In addition, we have reproduced in vitro the regulatory circuit in the proposed physiological direction, NAD(P)H-ThnA4-ThnA3-ThnY. ThnA3 represents an unprecedented way of communication between a catabolic pathway and its regulatory system to prevent gratuitous induction.

  16. Redox proteins of hydroxylating bacterial dioxygenases establish a regulatory cascade that prevents gratuitous induction of tetralin biodegradation genes

    PubMed Central

    Ledesma-García, Laura; Sánchez-Azqueta, Ana; Medina, Milagros; Reyes-Ramírez, Francisca; Santero, Eduardo

    2016-01-01

    Bacterial dioxygenase systems are multicomponent enzymes that catalyze the initial degradation of many environmentally hazardous compounds. In Sphingopyxis granuli strain TFA tetralin dioxygenase hydroxylates tetralin, an organic contaminant. It consists of a ferredoxin reductase (ThnA4), a ferredoxin (ThnA3) and a oxygenase (ThnA1/ThnA2), forming a NAD(P)H–ThnA4–ThnA3–ThnA1/ThnA2 electron transport chain. ThnA3 has also a regulatory function since it prevents expression of tetralin degradation genes (thn) in the presence of non-metabolizable substrates of the catabolic pathway. This role is of physiological relevance since avoids gratuitous and wasteful production of catabolic enzymes. Our hypothesis for thn regulation implies that ThnA3 exerts its action by diverting electrons towards the regulator ThnY, an iron-sulfur flavoprotein that together with the transcriptional activator ThnR is necessary for thn gene expression. Here we analyze electron transfer among ThnA4, ThnA3 and ThnY by using stopped-flow spectrophotometry and determination of midpoint reduction potentials. Our results indicate that when accumulated in its reduced form ThnA3 is able to fully reduce ThnY. In addition, we have reproduced in vitro the regulatory circuit in the proposed physiological direction, NAD(P)H–ThnA4–ThnA3–ThnY. ThnA3 represents an unprecedented way of communication between a catabolic pathway and its regulatory system to prevent gratuitous induction. PMID:27030382

  17. Effect of structural alteration on the macromolecular properties of brown and bituminous coals, quantitative relationships to the hydrogenation reactivity with tetralin

    SciTech Connect

    Kuznetsov, P.N.; Kuznetsova, L.I.; Bimer, J.; Salbut, P.D.; Gruber, R.

    1996-12-31

    The mobility of macromolecular network has been found to be the fundamental property of both brown and bituminous coals governing the reactivity for hydrogenation with tetralin. In Kansk-Achinsk brown coal, this was primarily affected by carboxylate cross-linking via polyvalent cations like Ca.

  18. cis-Diastereoselective synthesis of chroman-fused tetralins as B-ring-modified analogues of brazilin.

    PubMed

    Gogoi, Dimpee; Devi, Runjun; Pahari, Pallab; Sarma, Bipul; Das, Sajal Kumar

    2016-01-01

    We have synthesized a series of cis-6a,7,8,12b-tetrahydro-6H-naphtho[2,1-c]chromen-6a-ols as B-ring-modified analogues of (±)-brazilin. A completely regio- and cis-diastereoselective intramolecular Friedel-Crafts epoxy-arene cyclization of 1-tetralone-derived glycidyl ethers catalyzed by Brønsted acids was used as the key step. Our worries concerning the formation of cis-trans product mixtures and their probable conversion to naphthopyran derivatives via dehydration of the tertiary hydroxy group were laid to rest. Additionally, the angular hydroxy group of one of the synthesized products has been reductively removed by a diastereoselective method which should be useful in future for preparing libraries of chroman-fused tetralins with trans-stereochemistry at the ring junction.

  19. cis-Diastereoselective synthesis of chroman-fused tetralins as B-ring-modified analogues of brazilin

    PubMed Central

    Gogoi, Dimpee; Devi, Runjun; Pahari, Pallab; Sarma, Bipul

    2016-01-01

    We have synthesized a series of cis-6a,7,8,12b-tetrahydro-6H-naphtho[2,1-c]chromen-6a-ols as B-ring-modified analogues of (±)-brazilin. A completely regio- and cis-diastereoselective intramolecular Friedel–Crafts epoxy–arene cyclization of 1-tetralone-derived glycidyl ethers catalyzed by Brønsted acids was used as the key step. Our worries concerning the formation of cis–trans product mixtures and their probable conversion to naphthopyran derivatives via dehydration of the tertiary hydroxy group were laid to rest. Additionally, the angular hydroxy group of one of the synthesized products has been reductively removed by a diastereoselective method which should be useful in future for preparing libraries of chroman-fused tetralins with trans-stereochemistry at the ring junction. PMID:28144354

  20. Donor-Acceptor Cyclopropanes as 1,2-Dipoles in GaCl3-Mediated [4 + 2]-Annulation with Alkenes: Easy Access to the Tetralin Skeleton.

    PubMed

    Novikov, Roman A; Tarasova, Anna V; Korolev, Victor A; Shulishov, Evgeny V; Timofeev, Vladimir P; Tomilov, Yury V

    2015-08-21

    A new process for (4 + 2)-annulation of donor-acceptor cyclopropanes (DACs) with unsaturated compounds in the presence of anhydrous GaCl3 has been developed. In this process, DACs act as sources of formal 1,2- and 1,4-dipoles to give polysubstituted tetralins in high yields and with high regio- and diastereoselectivity. Alkenes with both aryl and alkyl substituents at the double bond undergo this reaction equally readily. A most likely mechanism of the reaction has been proposed. It involves preliminary generation of a key 1,2-dipolar gallium complex and its subsequent participation in annulation with an alkene.

  1. Flow pyrolysis and direct and silicon tetrafluoride-sensitized laser-induced decomposition of tetralin. Identification of retro-[2 + 4] cleavage as the primary homogeneous thermal decomposition channel

    SciTech Connect

    Berman, Michael R.; Comita, Paul B.; Moore, C. Bradley; Bergman, Robert G.

    1980-08-01

    In an effort to determine the products and mechanism of the truly homogeneous thermal decomposition of the aromatic hydrocarbon tetralin, we have examined the products formed from this compound upon energization by conventional flow pyrolysis, infrared multiphoton excitation, and SiF{sub 4}-sensitized infrared laser thermal activation. Six major products are formed in these reactions, but the product ratios depend upon the mode of energization. Flow pyrolysis gives a result analogous to those observed earlier; i.e. almost exclusive dehydrogenation, leading to dihydronaphthalene and naphthalene. Direct and sensitized IR laser-induced decomposition, however, leads to ethylene loss (presumably by an initial retro-[2+4] reaction) as the predominent decomposition mode, giving benzocyclobutene. We believe these results are due to the fact that direct thermal decomposition, both in our experiments as well as in previous studies, involves predominant surface-catalysis. In the laser-induced reactions, which are uncomplicated by problems due to surface-catalysis, the true homogeneous decomposition takes place, and this involves retro-[2+4] cleavage. Mechanistic details of these processes were studied by examining the isotope distribution in the products formed on SiF{sub 4}-sensitized laser photolysis of 1,1,4,4-tetradeuteriotetralin.

  2. 2-amino-nonyl-6-methoxyl-tetralin muriate activity against Candida albicans augments endogenous reactive oxygen species production --a microarray analysis study.

    PubMed

    Liang, Rong Mei; Yong, Xiao Lan; Jiang, Yun Ping; Tan, Yong Hong; Dai, Bao Di; Wang, Shi Hua; Hu, Ting Ting; Chen, Xi; Li, Nan; Dong, Zhao Hui; Huang, Xiao Chun; Chen, Jun; Cao, Yong Bing; Jiang, Yuan Ying

    2011-04-01

    Candida infections have become an increasingly significant problem, mainly because of the widespread nature of Candida and drug resistance. There is an urgent need to develop new classes of drugs for the treatment of opportunistic Candida infections, especially in medically complex patients. Previous studies have confirmed that 2-amino-nonyl-6-methoxyl-tetralin muriate (10b) possesses powerful antifungal activity in vitro against Candia albicans. To clarify the underlying action mechanism, an oligonucleotide microarray study was performed in C. albicans SC5314 without and with 10b treatment. The analytical results showed that energy metabolism-related genes, including glycolysis-related genes (PFK1, CDC19 and HXK2), fermentation-related genes (PDC11, ALD5 and ADH1) and respiratory electron transport chain-related genes (CBP3, COR1 and QCR8), were downregulated significantly. Functional analysis revealed that 10b treatment increased the generation of endogenous reactive oxygen species, and decreased mitochondrial membrane potential, ubiquinone-cytochrome c reductase (complex III) activity and intracellular ATP levels in C. albicans SC5314. Also, addition of the antioxidant ascorbic acid reduced the antifungal activity of 10b significantly. These results suggest that mitochondrial aerobic respiration shift and endogenous reactive oxygen species augmentation might contribute to the antifungal activity of 10b against C. albicans. This information may prove to be useful for the development of new strategies to treat Candida infections.

  3. The spleen is required for 5-HT1A receptor agonist-mediated increases in mean circulatory filling pressure during hemorrhagic shock in the rat.

    PubMed

    Tiniakov, Ruslan; Scrogin, Karie E

    2009-05-01

    The 5-HT(1A) receptor agonist, 8- OH-DPAT, increases whole body venous tone (mean circulatory filling pressure; MCFP), and attenuates metabolic acidosis in a rat model of unresuscitated hemorrhagic shock. To determine whether improved acid-base balance was associated with sympathetic activation and venous constriction, MCFP, sympathetic activity (SA), and blood gases were compared in hemorrhaged rats following administration of 5-HT(1A) receptor agonist 8-OH-DPAT, the arterial vasoconstrictor arginine vasopressin (AVP), or saline. To further determine whether protection of acid-base balance was dependent on splenic contraction and blood mobilization, central venous pressure (CVP), MCFP, and blood gases were determined during hemorrhage and subsequent 8-OH-DPAT-administration in rats subjected to real or sham splenectomy. Subjects were hemorrhaged to an arterial pressure of 50 mmHg for 25 min and subsequently were treated with 8-OH-DPAT (30 nmol/kg iv), AVP titrated to match the pressor effect of 8-OH-DPAT (approximately 2 ng/min iv), or infusion of normal saline. 8-OH-DPAT increased MAP, CVP, MCFP, and SA, and decreased lactate accumulation. AVP did not affect CVP or SA, but raised MCFP slightly to a level intermediate between 8-OH-DPAT- and saline-treated rats. Infusion of AVP also produced a modest protection against metabolic acidosis. Splenectomy prevented the rise in CVP, MCFP, and protection against metabolic acidosis produced by 8-OH-DPAT but had no effect on the immediate pressor response to the drug. Together, the data indicate that 8-OH-DPAT produces a pattern of cardiovascular responses consistent with a sympathetic-mediated venoconstriction that is, in part, responsible for the drug's beneficial effect on acid-base balance. Moreover, blood mobilization stimulated by the spleen is required for the beneficial effects of 8-OH-DPAT.

  4. RU 24969-induced emesis in the cat - 5-HT1 sites other than 5-HT1A, 5-HT1B or 5-HT1C implicated

    NASA Technical Reports Server (NTRS)

    Lucot, James B.

    1990-01-01

    RU 24969 was administered s.c. to cats and found to elicit emesis with a maximally effective dose of 1.0 mg/kg 5-Methoxytryptamine was found to have lower efficacy and to produce a higher incidence of nonspecific effects while trifluoromethylphenylpiperizine (TFMPP) was devoid of emetic effects. The emesis elicited by 1.0 mg/kg of RU 24969 was not altered by pretreatment with phentolamine, haloperidol, yohimbine or (-)-propranolol, indicating that catecholamines played no role in this response. The emesis was prevented by metergoline and methysergide but not by ketanserin, cyproheptadine, mesulergine, ICS 205 930, methiothepin, trimethobenzamide or BMY 7378. An indirect argument is presented that implicates a role for 5-HT1D sites. This conclusion must remain tentative until drugs selective for this site are synthesized and tested. The emesis was also prevented by 8-hydroxy-2-(di-n-propylamine)tetralin (8-OH-DPAT), confirming that this drug has a general antiemetic effect in cats.

  5. N-Methyl-1-(4-methoxyphenyl)-2-aminopropane (PMMA) and N-Methyl-1-(3,4-methylenedioxyphenyl)-2-aminopropane (MDMA) produce non-identical discriminative stimuli in rats.

    PubMed

    Glennon, Richard A; Young, Richard; Dukat, Małgorzata; Chang-Fong, Jean; El-Zahabi, Mohamed

    2007-03-01

    N-Methyl-1-(3,4-methylenedioxyphenyl)-2-aminopropane (methylenedioxymethamphetamine, MDMA, Ecstasy) and its structurally abbreviated congener N-methyl-1-(4-methoxyphenyl)-2-aminopropane (para-methoxymethamphetamine, PMMA) are chemically related designer drugs, and PMMA is sometimes sold on the clandestine market as a substitute for MDMA. Prior drug discrimination studies have found that MDMA and PMMA substitute for one another suggesting that they produce similar discriminative stimulus effects in rats. However, there also are some indications that the two agents produce distinct stimulus effects. In this study, further comparisons were made between the stimulus effects of these two agents. Sprague-Dawley rats were trained to discriminate either 1.25 mg/kg of PMMA or 1.5 mg/kg of MDMA from saline vehicle in a two-lever operant paradigm. A structure-activity comparison revealed that MDMA and PMMA behave similarly upon homologation of their terminal amine substituents. In contrast, the PMMA stimulus, unlike an MDMA stimulus, failed to generalize completely to the psychostimulant cocaine, 8-hydroxy-2-(N,N-di-n-propylamino)tetralin (8-OH DPAT), and R(-)-1-(3-methoxyphenyl)-2-aminopropane [R(-)MMA]. In an additional group of animals, a (+)amphetamine stimulus partially generalized to R(-)MMA. Taken together, the results argue and re-emphasize the conclusion that the stimulus effects produced by MDMA and PMMA are similar, but non-identical, and that PMMA is the less "stimulant-like" of the two.

  6. Decreased agonist, but not antagonist, binding to the naturally occurring Thr92Lys variant of the h5-HT7(a) receptor.

    PubMed

    Brüss, Michael; Kiel, Sibylle; Bönisch, Heinz; Kostanian, Arevat; Göthert, Manfred

    2005-08-01

    In the present study on transfected human embryonic kidney (HEK)293 cells, we aimed at establishing whether expression of the naturally occurring Thr92Lys variation of the Gs-coupled h5-HT7(a) receptor leads to changes of ligand binding properties, of agonist-evoked cAMP formation and/or of antagonist-mediated blockade of the latter. Binding of [3H]5-carboxamidotryptamine ([3H]5-CT) to membranes and stimulated [3H]cAMP accumulation in whole cells were determined. Saturation binding experiments in membranes of transiently transfected cells expressing either the wild-type or the variant receptor revealed a single binding site in both cases and no difference in Bmax between both receptor isoforms. In competition binding experiments in membranes of stably transfected cells, the Thr92Lys variant exhibited a 2.8-11 times lower binding affinity of the ligands 5-hydroxytryptamine (5-HT), 5-CT, 5-methoxy-3-(1,2,3,6-tetrahydropyridin-4yl)-1H-indole (RU24969), (+/-)-hydroxy-2-(di-n-propylamino)tetralin hydrobromide (8-OH-DPAT) and sumatriptan compared to the wild-type receptor. However, the variant did not differ from the wild-type with respect to the binding properties of the antagonists (R)-3-(2-(2-(4-methylpiperidin-1-yl)ethyl)-pyrrolodine-1-sulfonyl)phenol hydrochloride (SB-269970), risperidone, mesulergine and clozapine. In agreement with the decreased binding affinity of 5-HT, 5-CT, RU24969 and 8-OH-DPAT for the variant receptor, these agonists were less potent in stimulating [3H]cAMP accumulation in cells stably expressing the Thr92Lys h5-HT7(a) receptor. Sumatriptan did not stimulate cAMP accumulation in spite of its affinity for both receptor isoforms pointing to a putative weak antagonistic property of this drug at the h5-HT7 receptor. SB-269970 and clozapine were equipotent at both the variant and the wild-type receptor in producing a rightward shift of the 5-HT concentration-response curve for its stimulant effect on [3H]cAMP accumulation. In view of, e.g., the

  7. 5-HT1A receptor activation counteracted the effect of acute immobilization of noradrenergic neurons in the rat locus coeruleus.

    PubMed

    Rioja, José; Santín, Luis J; López-Barroso, Diana; Doña, Alicia; Ulzurrun, Eugenia; Aguirre, José A

    2007-01-22

    The aim of our study was to evaluate the effect of acute stress and the 5-HT(1A) receptor involvement in both, the hippocampus noradrenaline (NA) tissue levels and the c-Fos immunoreactivity (c-Fos-IR) in the catecholaminergic neurons of the locus coeruleus (LC). Double immunocytochemical staining of tyrosine hydroxilase (TH) and c-Fos protein combined with stereological techniques were used to study the specific cell activation in the LC neurons in five experimental groups (control group, immobilization (1h) group, 8-OH-DPAT group (8-OH-DPAT 0.3mg/kg, s.c.), DPAT+IMMO group (8-OH-DPAT 0.3mg/kg, s.c., 30' prior acute immobilization) and WAY+DPAT+IMMO group (WAY-100635 0.3mg/kg, s.c. and 8-OH-DPAT 0.3mg/kg, s.c., 45'and 30', respectively, before immobilization). The results showed that hippocampal NA tissue levels and c-Fos-IR in the TH positive neurons of the LC were significantly increased immediately and after 90', respectively, after the immobilization period. Pre-treatment with 8-OH-DPAT counteracted the effects induced by immobilization, but pre-treatment with WAY-100635 did not block the effects induced by 8-OH-DPAT. These results suggest that noradrenaline system is associated in a significant way with immobilization stress. The role of 5-HT(1A) receptor activation in this stress response is also discussed.

  8. Activation of 5-HT1A and 5-HT7 receptors in the parafascicular nucleus suppresses the affective reaction of rats to noxious stimulation.

    PubMed

    Harte, Steven E; Kender, Robert G; Borszcz, George S

    2005-02-01

    The antinociceptive effects of the serotonin (5-HT)1A/7 receptor agonist 8-hydroxy-dipropylaminotetralin (8-OH-DPAT) administered into the medial thalamus were evaluated. Pain behaviors organized at spinal (spinal motor reflexes, SMRs), medullary (vocalizations during shock, VDSs), and forebrain (vocalization after discharges, VADs) levels of the neuraxis were elicited by tailshock. Administration of 8-OH-DPAT (5, 10, and 20 microg/side) into nucleus parafascicularis (nPf) produced dose-dependent increases in VDS and VAD thresholds, but failed to elevate SMR threshold. The increase in VAD threshold was significantly greater than that of VDS threshold. Similar effects were observed with administration of 8-OH-DPAT (20 microg/side) into the rostral portion of the central lateral thalamic nucleus. The bilateral or unilateral administration of 8-OH-DPAT (20 microg) into other thalamic nuclei, or into sites dorsal to nPf, did not elevate vocalization thresholds. Increases in vocalization thresholds produced by nPf-administered 8-OH-DPAT were mediated by both 5-HT1A and 5-HT7 receptors. Intra-nPf administration of the 5-HT1A receptor antagonist WAY-100635 (0.05 or 0.5 microg/side), or the 5-HT7 receptor antagonist SB-269970 (1 or 2 microg/side), but not the dopamine D2 receptor antagonist raclopride (10 microg/side), reversed 8-OH-DPAT induced elevations in vocalization thresholds. These results provide the first reported evidence of behavioral antinociception following the administration of a 5-HT agonist into the medial thalamus.

  9. SCN Neurochemistry using In Vivo, Microdialysis in the Conscious Brain

    DTIC Science & Technology

    1993-12-27

    applied 8-OH-DPAT was abolished by i.p. injection of the 5 -HTIA receptor antagonist , NAN-190, administered 20 min before the 8-OH-DPAT. Localized perfusion...pretreatment levels; pɘ.05). This effect was prevented by i.p. injection of the non-selective 5 -HT receptor antagonist , metergoline 20 min before TFMPP...perfusion. Localized perfusion of the SCN region with the 5 -HT2 and 5 - HT3 receptor agonists, a-methyl 5 -HT and 1-phenylbiguanide respectively, had little

  10. Functional expression of 5-HT7 receptor on the substantia gelatinosa neurons of the trigeminal subnucleus caudalis in mice.

    PubMed

    Yang, Eun Ju; Han, Seong Kyu; Park, Soo Joung

    2013-10-25

    The substantia gelatinosa (SG) of the trigeminal subnucleus caudalis (Vc; medullary dorsal horn) receives and processes orofacial nociceptive inputs, and serotonergic fibers involved in the descending modulation of nociception are more densely distributed in the superficial laminae of the Vc. This study investigated the direct effects of 5-HT1A/7 receptor agonist 8-OH-DPAT on SG neurons of the Vc to assess functional expression of the 5-HT7 receptor using gramicidin-perforated patch-clamp in postnatal day (PND) 5-84 male mice. Of the 70 SG neurons tested, bath application of 8-OH-DPAT (30μM) induced depolarization (n=33), hyperpolarization (n=16) or no response (n=21). In another 10 SG neurons, 8-OH-DPAT in the presence of 5-HT1A receptor antagonist WAY-100635 (1μM) elicited either depolarization (n=6) or no response (n=4); hyperpolarization was not observed. The 8-OH-DPAT-induced depolarization was significantly blocked by the selective 5-HT7 receptor antagonist SB-269970 (10μM; n=8), but not by WAY-100635 (1μM; n=5). The depolarizing effect of 8-OH-DPAT was maintained in the presence of TTX, CNQX, AP5, picrotoxin, and strychnine, indicating direct postsynaptic action of 8-OH-DPAT on SG neurons (n=6). 5-HT7 receptor mRNA was also detected in five of 21 SG neurons by single-cell RT-PCR. The mean amplitude of 8-OH-DPAT-induced depolarization in PND 5-21 mice (n=21) was significantly larger than that in PND 22-84 mice (n=12), although the proportion of SG neurons responding to 8-OH-DPAT by depolarization did not differ significantly between two age groups of mice. These results indicate that 5-HT7 receptors are functionally expressed in a subpopulation of SG neurons of the Vc and activation of 5-HT7 receptors plays an important role in modulating orofacial nociceptive processing in the SG neurons of the Vc.

  11. Neurophysiological Analysis of Circadian Rhythm Entrainment

    DTIC Science & Technology

    1993-03-30

    Other putative 5-HTIA antagonists, 2 6 pindolol, spiperone and propranolol , were either weak or ineffective in blocking the action of 2 7 8-OH-DPAT...Neuron 4:477-485. 1 7 Shibata, S., S.Y. Liou and S. Ueki. (1986) Influence of excitatory amino acid receptor 1 8 antagonists and of baclofen on synaptic

  12. Decreased response of interneurons in the medial prefrontal cortex to 5-HT₁A receptor activation in the rat 6-hydroxydopamine Parkinson model.

    PubMed

    Zhang, Qiaojun; Wang, Shuang; Zhang, Lina; Zhang, Huan; Qiao, Hongfei; Niu, Xiaolin; Liu, Jian

    2014-08-01

    This study examined the response of interneurons in the medial prefrontal cortex (mPFC) to 5-HT1A receptor agonist 8-OH-DPAT and change in expression of 5-HT1A receptor on glutamate decarboxylase 67 (GAD67)-positive neurons in rats with 6-hydroxydopamine (6-OHDA) lesions of the substantia nigra pars compacta (SNc). Systemic administration of 5-HT1A receptor agonist 8-OH-DPAT dose-dependently inhibited the firing rate of the interneurons at all doses tested in sham-operated rats. In 6-OHDA-lesioned rats, 8-OH-DPAT, at the same doses, also inhibited the firing rate of the interneurons, whereas the inhibition was significant only at a high cumulative dose. Furthermore, injection of 8-OH-DPAT into the mPFC inhibited the interneurons in sham-operated rats, while having no effect on firing rate of the interneurons in 6-OHDA-lesioned rats. In contrast to sham-operated rats, SNc lesion reduced the expression of 5-HT1A receptor on GAD67-positive neurons in the prelimbic cortex, a sub-region of the mPFC. Our results indicate that degeneration of the nigrostriatal pathway leads to decreased response of mPFC interneurons to 5-HT1A receptor activation, which attributes to the down-regulation of 5-HT1A receptor expression in these interneurons.

  13. Striatal 5-HT1A receptor stimulation reduces D1 receptor-induced dyskinesia and improves movement in the hemiparkinsonian rat

    PubMed Central

    Dupre, Kristin B.; Eskow, Karen L.; Barnum, Christopher J.; Bishop, Christopher

    2008-01-01

    Summary Convergent evidence suggests that serotonin 5-HT1A receptor (5-HT1AR) agonists reduce L-DOPA-induced dyskinesia by auto-regulating aberrant release of L-DOPA-derived dopamine (DA) from raphestriatal neurons. However, recent findings indicate that 5-HT1AR stimulation also modifies D1 receptor (D1R)-mediated dyskinesia and rotations implicating a previously unexplored extra-raphe mechanism. In order to characterize the contribution of the striatum to these effects, rats with medial forebrain bundle DA lesions were tested for abnormal involuntary movements (AIMs) and rotations following striatal microinfusions of the 5-HT1AR agonist ±8-OH-DPAT and systemic D1R agonist treatment with SKF81297. Additional rats with multi-site striatal DA lesions were tested for motor disability following systemic or intrastriatal ±8-OH-DPAT with or without systemic SKF81297. In rats with medial forebrain bundle lesions, striatal infusions of ±8-OH-DPAT dose-dependently reduced AIMs while conversely increasing rotations. In rats with striatal lesions, ±8-OH-DPAT alone, both systemic and intrastriatal administration, optimally reversed motor disability. Collectively, these results support an important functional interaction between 5-HT1AR and D1R in the striatum with implications for the improved treatment of Parkinson’s disease. PMID:18824001

  14. The Metabolism of Tetralin in Fischer 344 Rats

    DTIC Science & Technology

    1986-04-01

    would die from the disease. The relevance of nephropathy observed in male rats exposed to various hydrocarbons to the occurrence of renal neoplasia in man...hydrocarbons develop dose-related nephropathies which are not observed in female rats and control rats or in the males and females of other animal...then held for long-term, post-exposure evaluation revealed tubular degeneration consistent with "old-rat nephropathy " (explained below). C. Chronic

  15. 5-HT1A receptor activation counteracts c-Fos immunoreactivity induced in serotonin neurons of the raphe nuclei after immobilization stress in the male rat.

    PubMed

    Rioja, José; Santín, Luis J; Doña, Alicia; de Pablos, Laura; Minano, Francisco J; Gonzalez-Baron, Salvador; Aguirre, Jose A

    2006-04-24

    The serotoninergic system and the 5-HT1A receptors have been involved in the brain response to acute stress. The aim of our study was evaluate the role of the 5-HT1A receptors in serotoninergic cells of rostral and caudal raphe nuclei under acute immobilization in rats. Double immunocytochemical staining of 5-hydroxy-tryptamine and c-Fos protein and stereology techniques were used to study the specific cell activation in the raphe nuclei neurons in five groups (control group, immobilization group (immobilization lasting 1 h), DPAT group (8-OH-DPAT 0.3 mg/kg, s.c.), DPAT+IMMO group (8-OH-DPAT 0.3 mg/kg, s.c., 30' prior acute immobilization) and WAY+DPAT+IMMO group (WAY-100635 0.3 mg/kg, s.c. and 8-OH-DPAT 0.3 mg/kg, s.c., 45' and 30', respectively, before immobilization). Our results showed an increase in the number of c-Fos immunoreactive nuclei in serotoninergic cells in both dorsal and median raphe nuclei in the immobilized group. The 8-OH-DPAT pretreatment counteracted the excitatory effects of the acute immobilization in these brain regions. In addition, WAY-100635 administration reduced the effect of 8-OH-DPAT injection, suggesting a selective 5-HT1A receptor role. Raphe pallidus and raphe obscurus did not show any differences among experimental groups. We suggest that somatodendritic 5-HT1A receptors in rostral raphe nuclei may play a crucial role in both mediating the consequences of uncontrollable stress and the possible beneficial effects of treatment with 5-HT1A receptor agonists.

  16. 5-HT1A receptors modulate the consolidation of learning in normal and cognitively impaired rats.

    PubMed

    Meneses, A; Hong, E

    1999-03-01

    Attempts were made to further analyze the role of 5-HT1A receptors in consolidation of learning by evaluating the role of these receptors in cognitively normal and impaired animals. The effects of post-training administration of 8-OH-DPAT and 5-HT1A receptor antagonists, WAY 100135, WAY 100635, and S-UH-301, plus the cholinergic and glutamatergic antagonists, scopolamine and dizolcipine, respectively, were determined using an autoshaping learning task. The results showed that 8-OH-DPAT increased the number of conditioned responses, whereas WAY100135, WAY100635, and S-UH-301, and the 5-HT depleter, p-chloroamphetamine (PCA), had no effect. PCA did not change the silent properties of the 5-HT1A receptor antagonists. PCA, WAY100635, and S-UH-301, but not GR127935 (a 5-HT1B/1D-receptor antagonist) or MDL100907 (a 5-HT2A receptor antagonist), reversed the effect to 8-OH-DPAT. Ketanserin (a 5-HT2A/2C receptor antagonist) and ondansetron (a 5-HT3 receptor antagonist), at a dose that increased the conditioned responses by itself, reversed the effect of 8-OH-DPAT. Moreover, 8-OH-DPAT or S-UH-301 reversed the learning deficit induced by scopolamine and dizocilpine whereas WAY100635 reversed the effect of scopolamine only. These data confirm a role for presynaptic 5-HT1A receptors during the consolidation of learning and support the hypothesis that serotonergic, cholinergic, and glutamatergic systems interact in cognitively impaired animals.

  17. Effects of 5-HT1A receptor stimulation on striatal and cortical M1 pERK induction by L-DOPA and a D1 receptor agonist in a rat model of Parkinson's disease.

    PubMed

    Lindenbach, David; Dupre, Kristin B; Eskow Jaunarajs, Karen L; Ostock, Corinne Y; Goldenberg, Adam A; Bishop, Christopher

    2013-11-06

    Motor symptoms of Parkinson's disease are commonly treated using l-DOPA although long-term treatment usually causes debilitating motor side effects including dyskinesias. A putative source of dyskinesia is abnormally high levels of phosphorylated extracellular-regulated kinase (pERK) within the striatum. In animal models, the serotonin 1A receptor agonist ±8-OH-DPAT reduces dyskinesia, suggesting it may exhibit efficacy through the pERK pathway. The present study investigated the effects of ±8-OH-DPAT on pERK density in rats treated with l-DOPA or the D1 receptor agonist SKF81297. Rats were given a unilateral dopamine lesion with 6-hydroxydopamine and primed with a chronic regimen of l-DOPA, SKF81297 or their vehicles. On the final test day, rats were given two injections: first with ±8-OH-DPAT, the D1 receptor antagonist SCH23390 or their vehicles, and second with l-DOPA, SKF81297 or their vehicles. Rats were then transcardially perfused for immunohistological analysis of pERK expression in the striatum and primary motor cortex. Rats showed greater dyskinesia in response to l-DOPA and SKF81297 after repeated injections. Although striatal pERK induction was similar between acute and chronic l-DOPA, SKF81297 caused the largest increase in striatal pERK after the first exposure. Neither compound alone affected motor cortex pERK. Surprisingly, in the ventromedial striatum, ±8-OH-DPAT potentiated l-DOPA-induced pERK; in the motor cortex, ±8-OH-DPAT potentiated pERK with l-DOPA or SKF81297. Our results support previous work that the striatal pERK pathway is dysregulated after dopamine depletion, but call into question the utility of pERK as a biomarker of dyskinesia expression.

  18. Analysis of the 5-HT1A receptor involvement in passive avoidance in the rat

    PubMed Central

    Misane, Ilga; Johansson, Christina; Ove Ögren, Sven

    1998-01-01

    The effects of the 5-HT2A/2C agonist DOB, the selective 5-HT1A agonist NDO 008 (3-dipropylamino-5-hydroxychroman), and the two enantiomers of the selective 5-HT1A agonist 8-OH-DPAT (R(+)-8-OH-DPAT and S(−)-8-OH-DPAT) were studied in a step-through passive avoidance (PA) test in the male rat.The 5-HT1A agonists injected prior to training (conditioning) produced a dose-dependent impairment of PA retention when examined 24 h later. R(+)-8-OH-DPAT was four times more effective than S(−)-8-OH-DPAT to cause an impairment of PA retention. Both NDO 008 and the two enantiomers of 8-OH-DPAT induced the serotonin syndrome at the dose range that produced inhibition of the PA response, thus, indicating activation of postsynaptic 5-HT1A receptors.Neither NDO 008 nor R(+)-8-OH-DPAT induced head-twitches, a behavioural response attributed to stimulation of postsynaptic 5-HT2A receptors. In contrast, DOB induced head-twitches at the 0.01 mg kg−1 dose while a 200 times higher dose was required to produce a significant impairment of PA retention.The impairment of PA retention induced by both NDO 008 and R(+)-8-OH-DPAT was fully blocked by the active S(+)- enantiomer of the selective 5-HT1A antagonist WAY 100135 and the mixed 5-HT1A/β-adrenoceptor antagonist L(−)-alprenolol. In contrast, the mixed 5-HT2A/2C antagonists ketanserin and pirenperone were found to be ineffective. Moreover, the β2-adrenoceptor antagonist ICI 118551, the β1-antagonist metoprolol as well as the mixed β-adrenoceptor blocker D(+)-alprenolol all failed to modify the deficit of PA retention by NDO 008 and R(+)-8-OH-DPAT. None of the 5-HT1A or 5-HT2A/2C receptor antagonists tested or the β-blockers altered PA retention by themselves.A 3 day pretreatment procedure (200+100+100 mg kg−1) with the tryptophan hydroxylase inhibitor p-chlorophenylalanine (PCPA) did not alter PA retention and did not prevent the inhibitory action of the 5-HT1A agonists, indicating that their effects on PA do not

  19. Inhibition of medullary raphe serotonergic neurons has age-dependent effects on the CO2 response in newborn piglets.

    PubMed

    Messier, Michelle L; Li, Aihua; Nattie, Eugene E

    2004-05-01

    Medullary raphé serotonergic neurons are chemosensitive in culture and are situated adjacent to blood vessels in the brain stem. Selective lesioning of serotonergic raphé neurons decreases the ventilatory response to systemic CO2 in awake and sleeping adult rats. Abnormalities in the medullary serotonergic system, including the raphé, have been implicated in the sudden infant death syndrome (48). In this study, we ask whether serotonergic neurons in the medullary raphé and extra-raphé regions are involved in the CO2 response in unanesthetized newborn piglets, 3-16 days old. Whole body plethysmography was used to examine the ventilatory response to 5% CO2 before and during focal inhibition of serotonergic neurons by 8-hydroxy-2-di-n-propylaminotetralin (8-OH-DPAT), a 5-HT1A receptor agonist. 8-OH-DPAT (10 or 30 mM in artificial cerebrospinal fluid) decreased the CO2 response in wakefulness in an age-dependent manner, as revealed by a linear regression analysis that showed a significant negative correlation (P < 0.001) between the percent change in the CO2 response and piglet age. Younger piglets showed an exaggerated CO2 response. Control dialysis with artificial cerebrospinal fluid had no significant effect on the CO2 response. Additionally, 8-OH-DPAT increased blood pressure and decreased heart rate independent of age (P < 0.05). Finally, sleep cycling was disrupted by 8-OH-DPAT, such that piglets were awake more and asleep less (P < 0.05). Because of the fragmentary sleep data, it was not possible to examine the CO2 response in sleep. Inhibition of serotonergic medullary raphé and extra-raphé neurons decreases ventilatory CO2 sensitivity and alters cardiovascular variables and sleep cycling, which may contribute to the sudden infant death syndrome.

  20. Concentration-Dependent Dual Mode of Zn Action at Serotonin 5-HT1A Receptors: In Vitro and In Vivo Studies.

    PubMed

    Satała, Grzegorz; Duszyńska, Beata; Stachowicz, Katarzyna; Rafalo, Anna; Pochwat, Bartlomiej; Luckhart, Christine; Albert, Paul R; Daigle, Mireille; Tanaka, Kenji F; Hen, René; Lenda, Tomasz; Nowak, Gabriel; Bojarski, Andrzej J; Szewczyk, Bernadeta

    2016-12-01

    Recent data has indicated that Zn can modulate serotonergic function through the 5-HT1A receptor (5-HT1AR); however, the exact mechanisms are unknown. In the present studies, radioligand binding assays and behavioural approaches were used to characterize the pharmacological profile of Zn at 5-HT1ARs in more detail. The influence of Zn on agonist binding to 5-HT1ARs stably expressed in HEK293 cells was investigated by in vitro radioligand binding methods using the agonist [(3)H]-8-OH-DPAT. The in vivo effects of Zn were compared with those of 8-OH-DPAT in hypothermia, lower lip retraction (LLR), 5-HT behavioural syndrome and the forced swim (FST) tests. In the in vitro studies, biphasic effects, which involved allosteric potentiation of agonist binding at sub-micromolar Zn concentrations and inhibition at sub-millimolar Zn concentrations, were found. The in vivo studies showed that Zn did not induce LLR or elements of 5-HT behavioural syndrome but blocked such effects induced by 8-OH-DPAT. Zn decreased body temperature in rats and mice; however, Zn failed to induce hypothermia in the 5-HT1A autoreceptor knockout mice. In the FST, Zn potentiated the effect of 8-OH-DPAT. However, in the FST performed with the 5-HT1A autoreceptor knockout mice, the anti-immobility effect of Zn was partially blocked. Both the binding and behavioural studies suggest a concentration-dependent dual mechanism of Zn action at 5-HT1ARs, with potentiation at low dose and inhibition at high dose. Moreover, the in vivo studies indicate that Zn can modulate both presynaptic and postsynaptic 5-HT1ARs; however, Zn's effects at presynaptic receptors seem to be more potent.

  1. Dorsomedial hypothalamus serotonin 1A receptors mediate a panic-related response in the elevated T-maze.

    PubMed

    Nascimento, Juliana O G; Kikuchi, Letícia Sumiko; de Bortoli, Valquíria Camin; Zangrossi, Hélio; Viana, Milena B

    2014-10-01

    The dorsomedial hypothalamus (DMH) has long been associated with the regulation of escape, a panic-related defensive response. Previous evidence has shown that the activation of serotonin (5-HT) 1A and 2A receptors impairs escape behavior induced by the electrical stimulation of the same region. In this study we further explore the relationship of the DMH with defense by investigating the effects of 5-HT1A activation on escape behavior generated in male Wistar rats by an ethologically based aversive stimuli, exposure to one of the open arms of the elevated T-maze (ETM). Aside from escape, the ETM also allows the measurement of inhibitory avoidance, a defensive response associated with generalized anxiety disorder. To evaluate locomotor activity, after ETM measurements animals were submitted to an open field. Results showed that intra-DMH administration of the 5-HT1A receptor agonist 8-OH-DPAT inhibited escape expression. Local administration of the 5-HT1A antagonist WAY-100635 by its own was ineffective, but blocked the panicolytic-like effect of 8-OH-DPAT. Chronic (21 days) systemic treatment with imipramine potentiated the anti-escape effect of 8-OH-DPAT. No significant effects of treatment with 8-OH-DPAT or imipramine on avoidance latencies or the number of lines crossed in the open field were found. These results indicate that 5-HT1A receptors within the DMH may play a phasic inhibitory role on ETM escape expression. As previously proposed, facilitation of 5-HT1A-mediated neurotransmission in the DMH may be involved in the mechanism of action of anti-panic compounds.

  2. Effect of selective agonist of serotonin 5-HT1A receptors on defensive behavior in mice with different predisposition to catalepsy.

    PubMed

    Bazovkina, D V; Terenina, E E; Kulikov, A V

    2010-12-01

    We studied the effect of activation of serotonin 5-HT1A receptors with selective agonist 8-OH-DPAT (0.1, 0.5, and 1.0 mg/kg) on intraspecies aggression and freezing reaction (catalepsy) in male mice of catalepsy-resistant AKR/J and two catalepsy-prone strains CBA/Lac and congenic AKR.CBA-D13Mit76. The latter strain differs from AKR strain only by terminal chromosome 13 fragment transferred from CBA strain and containing a locus determining predisposition to catalepsy and a gene encoding 5-HT1A receptor. 8-OH-DPAT in a low dose (0.1 mg/kg) affecting primarily presynaptic receptors suppressed aggressive behavior in CBA mice, but had no effect on the time of cataleptic freezing. At the same time, this dose of the drug produced no significant effect on aggression in AKR and AKR.CBA-D13Mit76 mice, but significantly attenuated freezing in AKR.CBA-D13Mit76 mice. High doses of 8-OH-DPAT (0.5 and 1 mg/kg) which affected mainly postsynaptic receptors inhibited catalepsy in CBA and AKR.CBA-D13Mit76 mice and in a dose of 1 mg/kg it suppressed aggression in all tested mouse strains. We concluded that the genome of the recipient strain (AKR) modulated the involvement of 5-HT(1A) receptors into the regulation of aggression and catalepsy in mice.

  3. Desensitization of 5-HT(1A) autoreceptors induced by neonatal DSP-4 treatment.

    PubMed

    Dabrowska, Joanna; Nowak, Przemysław; Brus, Ryszard

    2007-01-15

    To examine the effect of noradrenergic lesion on the reactivity of central 5-HT(1A) receptors, DSP-4 (50 mg/kg) was administered neonatally 30 min after zimelidine (10 mg/kg) administration. 5-HT(1A) autoreceptors are involved in the regulation of serotonin (5-HT) synthesis. In HPLC assay R-(+)-8-OH-DPAT (0.03 mg/kg) significantly decreased 5-HT synthesis rate in striatum, hypothalamus and frontal cortex of control, whilst nonsignificantly in DSP-4-lesioned adult rats (10-12 weeks old). To determine which type of receptor, pre- or postsynaptically located, is involved in the attenuated response to 5-HT(1A) receptors' agonist, behavioral tests were conducted. R-(+)-8-OH-DPAT (0.015 mg/kg) caused hyperphagia of control rats, but did not change feeding of DSP-4 treated rats. R-(+)-8-OH-DPAT (0.1 mg/kg) induced hypothermia and "5-HT(1A) syndrome" in both control and DSP-4-lesioned animals. The nature of this phenomenon is attributable to the presynaptic adaptive mechanism and suggests the desensitization of 5-HT(1A) autoreceptors of rats with neonatal lesion of the central noradrenergic system.

  4. Serotonin 1A receptors and sexual behavior in a genetic model of depression.

    PubMed

    Schijven, D; Sousa, V C; Roelofs, J; Olivier, B; Olivier, J D A

    2014-06-01

    The Flinder Sensitive Line (FSL) is a rat strain that displays distinct behavioral and neurochemical features of major depression. Chronic selective serotonin reuptake inhibitors (SSRIs) are able to reverse these symptoms in FSL rats. It is well known that several abnormalities in the serotonergic system have been found in FSL rats, including increased 5-HT brain tissue levels and reduced 5-HT synthesis. SSRIs are known to exert (part of) their effects by desensitization of the 5-HT₁A receptor and FSL rats appear to have lower 5-HT1A receptor densities compared with Flinder Resistant Line (FRL) rats. We therefore studied the sensitivity of this receptor on the sexual behavior performance in both FRL and FSL rats. First, basal sexual performance was studied after saline treatment followed by treatment of two different doses of the 5-HT₁A receptor agonist ±8-OH-DPAT. Finally we measured the effect of a 5-HT₁A receptor antagonist to check for specificity of the 5-HT₁A receptor activation. Our results show that FSL rats have higher ejaculation frequencies compared with FRL rats which do not fit with a more depressive-like phenotype. Moreover FRL rats are more sensitive to effects of ±8-OH-DPAT upon EL and IF than FSL rats. The blunted response of FSL rats to the effects of ±8-OH-DPAT may be due to lower densities of 5-HT₁A receptors.

  5. Effects of the 5-HT(6) receptor antagonist Ro 04-6790 on learning consolidation.

    PubMed

    Meneses, A

    2001-01-08

    The 5-HT(6) receptor antagonist Ro-04-6790 or 8-OH-DPAT injection improved learning consolidation on an autoshaping task, while mCPP, scopolamine and dizocilpine decreased the performance. The effect induced by scopolamine, but not that induced by mCPP, was reversed completely by Ro-04-6790, while dizocilpine effect was antagonized partially. Nevertheless, ritanserin or WAY 100635, but not Ro 04-6790, antagonized the 8-OH-DPAT facilitatory effects on learning consolidation. As WAY 100635 did not modify the Ro 04-6790 facilitatory effect, hence 5-HT(1A), and/or 5-HT(7), but not 5-HT(6), receptors might mediate the 8-OH-DPAT facilitatory effect on learning consolidation. Since, the Ro 04-6790 facilitatory effect was unaffected by 5-HT(1A), 5-HT(2A)/(2B)/(2C), 5-HT(3) or 5-HT(4) receptor blockade, thereby, the facilitatory effect induced by Ro 04-6790 involved specifically 5-HT(6) receptors. Indeed, the present data provide further support to the notion that, 5-HT(6) receptors play a significant part in the learning consolidation under normal and dysfunctional memory conditions.

  6. The 5-HT1-like receptors mediating inhibition of sympathetic vasopressor outflow in the pithed rat: operational correlation with the 5-HT1A, 5-HT1B and 5-HT1D subtypes

    PubMed Central

    Villalón, Carlos M; Centurión, David; Rabelo, Gonzalo; de Vries, Peter; Saxena, Pramod R; Sánchez-López, Araceli

    1998-01-01

    It has been suggested that the inhibition of sympathetically-induced vasopressor responses produced by 5-hydroxytryptamine (5-HT) in pithed rats is mediated by 5-HT1-like receptors. The present study has re-analysed this suggestion with regard to the classification schemes recently proposed by the NC-IUPHAR subcommittee on 5-HT receptors.Intravenous (i.v.) continuous infusions of 5-HT and the 5-HT1 receptor agonists, 8-OH-DPAT (5-HT1A), indorenate (5-HT1A), CP 93,129 (5-HT1B) and sumatriptan (5-HT1B/1D), resulted in a dose-dependent inhibition of sympathetically-induced vasopressor responses.The sympatho-inhibitory responses induced by 5-HT, 8-OH-DPAT, indorenate, CP 93,129 or sumatriptan were analysed before and after i.v. treatment with blocking doses of the putative 5-HT receptor antagonists, WAY 100635 (5-HT1A), cyanopindolol (5-HT1A/1B) or GR 127935 (5-HT1B/1D). Thus, after WAY 100635, the responses to 5-HT and indorenate, but not to 8-OH-DPAT, CP 93,129 and sumatriptan, were blocked. After cyanopindolol, the responses to 5-HT, indorenate and CP 93,129 were abolished, whilst those to 8-OH-DPAT and sumatriptan (except at the lowest frequency of stimulation) remained unaltered. In contrast, after GR 127935, the responses to 5-HT, CP 93,129 and sumatriptan, but not to 8-OH-DPAT and indorenate, were abolished.In additional experiments, the inhibition induced by 5-HT was not modified after 5-HT7 receptor blocking doses of mesulergine.The above results suggest that the 5-HT1-like receptors, which inhibit the sympathetic vasopressor outflow in pithed rats, display the pharmacological profile of the 5-HT1A, 5-HT1B and 5-HT1D, but not that of 5-HT7, receptors. PMID:9692787

  7. Role of spinal serotonergic pathways in sneeze-induced urethral continence reflex in rats.

    PubMed

    Miyazato, Minoru; Kaiho, Yasuhiro; Kamo, Izumi; Kitta, Takeya; Chancellor, Michael B; Sugaya, Kimio; Arai, Yoichi; de Groat, William C; Yoshimura, Naoki

    2009-10-01

    To clarify the role of spinal serotonergic mechanisms in preventing stress urinary incontinence (SUI) during sneezing, we investigated the effect of intrathecal (it) application of 8-OH-DPAT (a 5-HT(1A) agonist), mCPP (a 5-HT(2B/2C) agonist), and fluoxetine (a serotonin reuptake inhibitor) using a rat model that can examine the neurally evoked continence reflex during sneezing. Amplitudes of urethral pressure responses during sneezing (A-URS), urethral baseline pressure (UBP) at the midurethra, and sneeze-induced leak point pressure (S-LPP) were measured in normal female adult rats and rats with SUI induced by vaginal distention (VD). In normal rats, 8-OH-DPAT decreased A-URS by 48.9%, whereas mCPP increased A-URS by 33.6%. However, A-URS was not changed after fluoxetine. 8-OH-DPAT, mCPP, or fluoxetine did not alter UBP. The effect of 8-OH-DPAT and mCPP was antagonized by WAY-100635 (it), a selective 5-HT(1A) antagonist, and RS-102221 (it), a selective 5-HT(2C) antagonist, respectively. Fluoxetine in the presence of WAY-100635 did not change either A-URS or UBP, but fluoxetine in the presence of RS-102221 decreased A-URS. In VD rats, S-LPP was decreased by 14.6 cmH2O after 8-OH-DPAT, whereas it was increased by 12.8 cmH2O after mCPP. However, S-LPP was not changed after fluoxetine. These results indicate that activation of 5-HT(2C) receptors enhances the active urethral closure reflex during sneezing at the spinal level, whereas 5-HT(1A) inhibits it and that no apparent changes in the sneeze-induced continence reflex after fluoxetine treatment are due to coactivation of excitatory 5-HT(2C) receptors and inhibitory 5-HT receptors other than the 5-HT(1A) subtype. Thus, activation of excitatory 5-HT receptor subtypes such as 5-HT(2C) could be effective for the treatment of SUI.

  8. Effects of 5-HT1A Receptor Stimulation on D1 Receptor Agonist-Induced Striatonigral Activity and Dyskinesia in Hemiparkinsonian Rats

    PubMed Central

    2013-01-01

    Accumulating evidence supports the value of 5-HT1A receptor (5-HT1AR) agonists for dyskinesias that arise with long-term L-DOPA therapy in Parkinson’s disease (PD). Yet, how 5-HT1AR stimulation directly influences the dyskinetogenic D1 receptor (D1R)-expressing striatonigral pathway remains largely unknown. To directly examine this, one cohort of hemiparkinsonian rats received systemic injections of Vehicle + Vehicle, Vehicle + the D1R agonist SKF81297 (0.8 mg/kg), or the 5-HT1AR agonist ±8-OH-DPAT (1.0 mg/kg) + SKF81297. Rats were examined for changes in abnormal involuntary movements (AIMs), rotations, striatal preprodynorphin (PPD), and glutamic acid decarboxylase (GAD; 65 and 67) mRNA via RT-PCR. In the second experiment, hemiparkinsonian rats received intrastriatal pretreatments of Vehicle (aCSF), ±8-OH-DPAT (7.5 mM), or ±8-OH-DPAT + the 5-HT1AR antagonist WAY100635 (4.6 mM), followed by systemic Vehicle or SKF81297 after which AIMs, rotations, and extracellular striatal glutamate and nigral GABA efflux were measured by in vivo microdialysis. Results revealed D1R agonist-induced AIMs were reduced by systemic and intrastriatal 5-HT1AR stimulation while rotations were enhanced. Although ±8-OH-DPAT did not modify D1R agonist-induced increases in striatal PPD mRNA, the D1R/5-HT1AR agonist combination enhanced GAD65 and GAD67 mRNA. When applied locally, ±8-OH-DPAT alone diminished striatal glutamate levels while the agonist combination increased nigral GABA efflux. Thus, presynaptic 5-HT1AR stimulation may attenuate striatal glutamate levels, resulting in diminished D1R-mediated dyskinetic behaviors, but maintain or enhance striatal postsynaptic factors ultimately increasing nigral GABA levels and rotational activity. The current findings offer a novel mechanistic explanation for previous results concerning 5-HT1AR agonists for the treatment of dyskinesia. PMID:23496922

  9. 5-HT(1A) and 5-HT(7) receptors differently modulate AMPA receptor-mediated hippocampal synaptic transmission.

    PubMed

    Costa, L; Trovato, C; Musumeci, S A; Catania, M V; Ciranna, L

    2012-04-01

    We have studied the effects of 5-HT(1A) and 5-HT(7) serotonin receptor activation in hippocampal CA3-CA1 synaptic transmission using patch clamp on mouse brain slices. Application of either 5-HT or 8-OH DPAT, a mixed 5-HT(1A)/5-HT(7) receptor agonist, inhibited AMPA receptor-mediated excitatory post synaptic currents (EPSCs); this effect was mimicked by the 5-HT(1A) receptor agonist 8-OH PIPAT and blocked by the 5-HT(1A) antagonist NAN-190. 8-OH DPAT increased paired-pulse facilitation and reduced the frequency of mEPSCs, indicating a presynaptic reduction of glutamate release probability. In another group of neurons, 8-OH DPAT enhanced EPSC amplitude but did not alter paired-pulse facilitation, suggesting a postsynaptic action; this effect persisted in the presence of NAN-190 and was blocked by the 5-HT(7) receptor antagonist SB-269970. To confirm that EPSC enhancement was mediated by 5-HT(7) receptors, we used the compound LP-44, which is considered a selective 5-HT(7) agonist. However, LP-44 reduced EPSC amplitude in most cells and instead increased EPSC amplitude in a subset of neurons, similarly to 8-OH DPAT. These effects were respectively antagonized by NAN-190 and by SB-269970, indicating that under our experimental condition LP-44 behaved as a mixed agonist. 8-OH DPAT also modulated the current evoked by exogenously applied AMPA, inducing either a reduction or an increase of amplitude in distinct neurons; these effects were respectively blocked by 5-HT(1A) and 5-HT(7) receptor antagonists, indicating that both receptors exert a postsynaptic action. Our results show that 5-HT(1A) receptors inhibit CA3-CA1 synaptic transmission acting both pre- and postsynaptically, whereas 5-HT(7) receptors enhance CA3-CA1 synaptic transmission acting exclusively at a postsynaptic site. We suggest that a selective pharmacological targeting of either subtype may be envisaged in pathological loss of hippocampal-dependent cognitive functions. In this respect, we underline the

  10. Contribution of the Striatum to the Effects of 5-HT1A Receptor Stimulation in L-DOPA-treated Hemiparkinsonian Rats

    PubMed Central

    Bishop, Christopher; Krolewski, David M.; Eskow, Karen L.; Barnum, Christopher J.; Dupre, Kristin B.; Deak, Terrence; Walker, Paul D.

    2009-01-01

    Clinical and experimental studies implicate the use of serotonin (5-HT)1A receptor agonists for the reduction of l-3,4-dihydroxyphenylalanine (L-DOPA)-induced dyskinesia (LID). Although raphe nuclei likely play a role in these antidyskinetic effects, an unexplored population of striatal 5-HT1A receptors (5-HT1AR) may also contribute. To better characterize this mechanism, L-DOPA-primed hemiparkinsonian rats received the 5-HT1AR agonist ±8-OH-DPAT (0, 0.1, 1.0 mg/kg, i.p.) with or without cotreatment with the 5-HT1AR antagonist WAY100635 (0.5 mg/kg, i.p.) 5 min after L-DOPA, after which abnormal involuntary movements (AIMs), rotations, and forelimb akinesia were quantified. To establish the effects of 5-HT1AR stimulation on L-DOPA-induced c-fos and preprodynorphin (PPD) mRNA within the dopamine-depleted striatum, immunohistochemistry and real-time reverse transcription polymerase chain reaction, respectively, were used. Finally, to determine the contribution of striatal 5-HT1AR to these effects, L-DOPA-primed hemiparkinsonian rats received bilateral intrastriatal microinfusions of ±8-OH-DPAT (0, 5, or 10 μg/side), WAY100635 (5 μg/side), or both (10 μg + 5 μg/side) 5 min after L-DOPA, after which AIMs and rotations were examined. Systemic ±8-OH-DPAT dose- and receptor-dependently attenuated L-DOPA-mediated AIMs and improved forelimb akinesia. Striatal c-fos immuno-reactivity and PPD mRNA ipsilateral to the lesion were strongly induced by L-DOPA, while ±8-OH-DPAT suppressed these effects. Finally, intrastriatal infusions of ±8-OH-DPAT reduced AIMs while coinfusion of WAY100635 reversed its antidyskinetic effect. Collectively, these results support the hypothesis that the cellular and behavioral properties of 5-HT1AR agonists are conveyed in part via a population of functional 5-HT1AR within the striatum. PMID:19115412

  11. A Study of the Nephrotoxicity and Metabolism of Tetralin and Indan in Fischer 344 Rats

    DTIC Science & Technology

    1989-05-01

    develop renal cancer and 8,900 would die from the disease. The relevance of nephropathy observed in male rats exposed to various hydrocarbons to the... nephropathies which are not observed in female rats and control rats or in the males and females of other animal species. These lesions seem to be...evaluation revealed tubular degeneration consistent with "old-rat nephropathy " (explained below). C. Chronic Exposures: Many chronic hydrocarbon

  12. A Study of the Nephrotoxicity and Metabolism of Tetralin and Indan in Fischer 344 Rats.

    DTIC Science & Technology

    1988-02-08

    nephropathy observed in male rats exposed to various hydrocarbons to the occurrence of renal neoplasia in man is of concern. Anatomic and physiologic...develop dose-related nephropathies which are not observed in female rats and control rats or in the males and females of other animal species. These...long-term, post-exposure evaluation revealed tubular degeneration consistent with "old-rat nephropathy " (explained below). C. Chronic Exposures: Many

  13. Vibrational study of polymorphism of tetralin derivative for treatment of cardiovascular diseases.

    PubMed

    Taddei, Paola; Torreggiani, Armida; Fini, Giancarlo

    2002-01-01

    Vibrational spectroscopy coupled with thermogravimetry (TG) and differential scanning calorimetry (DSC) was used to characterize racemic propanoic acid, 2-methyl-5,6,7,8-tetrahydro-6-(methylamino)-1,2-naphthalenediyl ester hydrochloride (CHF-1035), which is a new DA2 dopaminergic receptor/alpha2 agonist and beta blocker under clinical investigation for the treatment of congestive heart failure. Raman spectroscopy disclosed at least two different CHF-1035 polymorphs; the marker bands characteristic of each form were identified. The modifications undergone by the CHF-1035 drug as a consequence of grinding and heating were investigated. Mechanical and gentle thermal treatments caused a polymorphic transformation of the drug crystal form. Raman spectroscopy proved suitable for investigating the possible presence of different polymorphic forms, their relative stability, and interconversion tendency in relation to industrial manufacturing processes undergone by the drug (i.e., grinding, compression, and heating).

  14. Side effect profile of 5-HT treatments for Parkinson's disease and L-DOPA-induced dyskinesia in rats

    PubMed Central

    Lindenbach, D; Palumbo, N; Ostock, C Y; Vilceus, N; Conti, M M; Bishop, C

    2015-01-01

    BACKGROUND AND PURPOSE Treatment of Parkinson's disease (PD) with L-DOPA eventually causes abnormal involuntary movements known as dyskinesias in most patients. Dyskinesia can be reduced using compounds that act as direct or indirect agonists of the 5-HT1A receptor, but these drugs have been reported to worsen PD features and are known to produce ‘5-HT syndrome’, symptoms of which include tremor, myoclonus, rigidity and hyper-reflexia. EXPERIMENTAL APPROACH Sprague-Dawley rats were given unilateral nigrostriatal dopamine lesions with 6-hydroxydopamine. Each of the following three purportedly anti-dyskinetic 5-HT compounds were administered 15 min before L-DOPA: the full 5-HT1A agonist ±-8-hydroxy-2-dipropylaminotetralin (±8-OH-DPAT), the partial 5-HT1A agonist buspirone or the 5-HT transporter inhibitor citalopram. After these injections, animals were monitored for dyskinesia, 5-HT syndrome, motor activity and PD akinesia. KEY RESULTS Each 5-HT drug dose-dependently reduced dyskinesia by relatively equal amounts (±8-OH-DPAT ≥ citalopram ≥ buspirone), but 5-HT syndrome was higher with ±8-OH-DPAT, lower with buspirone and not present with citalopram. Importantly, with or without L-DOPA, all three compounds provided an additional improvement of PD akinesia. All drugs tempered the locomotor response to L-DOPA suggesting dyskinesia reduction, but vertical rearing was reduced with 5-HT drugs, potentially reflecting features of 5-HT syndrome. CONCLUSIONS AND IMPLICATIONS The results suggest that compounds that indirectly facilitate 5-HT1A receptor activation, such as citalopram, may be more effective therapeutics than direct 5-HT1A receptor agonists because they exhibit similar anti-dyskinesia efficacy, while possessing a reduced side effect profile. PMID:25175895

  15. The effect of serotonergic system on nociceptin/orphanin FQ induced food intake in chicken.

    PubMed

    Zendehdel, Morteza; Mokhtarpouriani, Kasra; Babapour, Vahab; Baghbanzadeh, Ali; Pourrahimi, Maryam; Hassanpour, Shahin

    2013-07-01

    The present study was designed to examine the effects of intracerebroventricular injection of para-chlorophenylalanine (PCPA) (cerebral serotonin depletive), fluoxetine (selective serotonin reuptake inhibitor), 8-OH-DPAT (5-HT1A autoreceptor agonist) and SB 242084 (5-HT2c receptor antagonist) on nociceptin/orphanin FQ (N/OFQ) induced feeding response in chickens. A guide cannula was surgically implanted into the lateral ventricle of chickens. Before the experiments, 3-h fasting periods had been given to all experimental birds. In experiment 1, chickens were injected with PCPA (1.5 μg) followed by an N/OFQ injection (16 nmol) intracerebroventricularly. In experiment 2, birds received fluoxetine (10 μg) prior to the injection of N/OFQ. In experiment 3, chickens were administered with N/OFQ after the 8-OH-DPAT administration (15.25 nmol). In experiment 4, birds were injected with SB 242084 (1.5 μg) followed by an N/OFQ injection. Cumulative food intake was measured at 3 h post injection. The results of this study show that N/OFQ increases food intake in broiler cockerels (P < 0.05) and that this effect is amplified by pretreatment with PCPA and SB 242084 in an additive manner (P < 0.05). The effect of N/OFQ is not changed by pretreatment with 8-OH-DPAT (P > 0.05). Furthermore, the stimulatory effect of N/OFQ on food intake was significantly attenuated by pretreatment with fluoxetine. These results suggest that N/OFQ induced hyperphagia is mediated by serotonergic mechanisms, and possibly imply an interaction between N/OFQ and the serotonergic system (via 5-HT2C receptors) on food intake in chickens.

  16. Unilateral lesion of the nigrostriatal pathway decreases the response of fast-spiking interneurons in the medial prefrontal cortex to 5-HT1A receptor agonist and expression of the receptor in parvalbumin-positive neurons in the rat.

    PubMed

    Gui, Z H; Zhang, Q J; Liu, J; Zhang, L; Ali, U; Hou, C; Fan, L L; Sun, Y N; Wu, Z H; Hui, Y P

    2011-10-01

    5-Hydroxytryptamine(1A) (5-HT(1A)) receptors are expressed in the prefrontal cortical interneurons. Among these interneurons, calcium-binding protein parvalbumin (PV)-positive fast spiking (FS) interneurons play an important role in regulatory function of the prefrontal cortex. In the present study, the response of medial prefrontal cortex (mPFC) FS interneurons to the selective 5-HT(1A) receptor agonist 8-OH-DPAT and change in expression of 5-HT(1A) receptor on PV-positive neurons were examined in rats with 6-hydroxydopamine (6-OHDA) lesions of the substantia nigra pars compacta (SNc) by using extracellular recording and double-labeling immunofluorescence histochemistry. Systemic administration of 8-OH-DPAT (1-243 μg/kg, i.v.) dose-dependently inhibited the mean firing rate of the FS interneurons in sham-operated and the lesioned rats, respectively. The cumulative doses producing inhibition in the lesioned rats (243 μg/kg) was significantly higher than that of sham-operated rats (27 μg/kg). Furthermore, the local application of 8-OH-DPAT (0.01 μg) in the mPFC inhibited the FS interneurons in sham-operated rats, while having no effect on firing rate of the FS interneurons in the lesioned rats. In contrast to sham-operated rats, the lesion of the SNc in rats did not cause the change of PV-positive neurons in the prelimbic prefrontal cortex, a subregion of the mPFC, whereas the lesion of the SNc markedly reduced in percentage of PV-positive neurons expressing 5-HT(1A) receptors. Our results indicate that degeneration of the nigrostriatal pathway results in the decreased response of FS interneurons in the mPFC to 5-HT(1A) receptor stimulation, which attributes to down-regulation of 5-HT(1A) receptor expression in these interneurons.

  17. Brown adipose tissue sympathetic nerve activity is potentiated by activation of 5-hydroxytryptamine (5-HT)1A/5-HT7 receptors in the rat spinal cord

    PubMed Central

    Madden, C. J.; Morrison, S. F.

    2008-01-01

    In urethane-chloralose anesthetized, neuromuscularly blocked, ventilated rats, microinjection of NMDA (12 pmol) into the right fourth thoracic segment (T4) spinal intermediolateral nucleus (IML) immediately increased ipsilateral brown adipose tissue (BAT) sympathetic nerve activity (SNA; peak +492% of control), expired CO2 (+0.1%) heart rate (+48 beats min−1) and arterial pressure (+8 mmHg). The increase in BAT SNA evoked by T4 IML microinjection of NMDA was potentiated when it was administered immediately following a T4 IML microinjection of 5-hydroxytryptamine (5-HT, 100 pmol) or the 5-HT1A/5-HT7 receptor agonist, 8-OH-DPAT (600 pmol), (area under the curve: 184%, and 259% of the NMDA-only response, respectively). In contrast, T4 IML microinjection of the 5-HT2 receptor agonist, DOI (28 pmol) did not potentiate the NMDA-evoked increase in BAT SNA (101% of NMDA-only response). Microinjection into the T4 IML of the selective 5-HT1A antagonist, WAY-100635 (500 pmol), plus the 5-HT7 antagonist, SB-269970 (500 pmol), prevented the 5-HT-induced potentiation of the NMDA-evoked increase in BAT SNA. When administered separately, WAY-100635 (800 pmol) and SB-269970 (800 pmol) attenuated the 8-OH-DPAT-induced potentiation of the NMDA-evoked increase in BAT SNA through effects on the amplitude and duration of the response, respectively. The selective 5-HT2 receptor antagonist, ketanserin (100 pmol), did not attenuate the potentiations of the NMDA-evoked increase in BAT SNA induced by either 5-HT or 8-OH-DPAT. These results demonstrate that activation of 5-HT1A/5-HT7 receptors can act synergistically with NMDA receptor activation within the IML to markedly increase BAT SNA. PMID:18082230

  18. The effect of urapidil, an alpha-1 adrenoceptor antagonist and a 5-HT1A agonist, on the vascular tone of the porcine coronary and pulmonary arteries, the rat aorta and the human pulmonary artery.

    PubMed

    Bopp, Claire; Auger, Cyril; Diemunsch, Pierre; Schini-Kerth, Valérie

    2016-05-15

    Urapidil (Eupressyl(®)) an antihypertensive drug acting as an α1 antagonist and a 5-HT1A agonist, may be of special interest in the treatment of hypertension associated with preeclamptic toxaemia and hypoxia-induced pulmonary arterial vasoconstriction. However, the effect of urapidil on vascular tone has been poorly investigated. Vascular reactivity was evaluated using pulmonary and coronary arteries from 36 pigs, aortae from 22 rats and 9 human pulmonary artery samples suspended in organ chambers. Concentration-relaxation curves either to urapidil, 5-HT, or the 5-HT1A receptor agonist 8-OH-DPAT were constructed after pre-contraction of rings. Pig pulmonary and coronary artery rings were contracted with U46619, a thromboxane mimetic, rat aortic rings with either endothelin-1 or phenylephrine, and human pulmonary artery rings with U46619 or phenylephrine. Urapidil markedly inhibited phenylephrine-induced contractions in rat aortic rings with and without endothelium with a more pronounced effect observed in rings without endothelium. Both 5-HT and 8-OH-DPAT failed to induce relaxation in rat aortic rings with an intact endothelium. 5-HT, but not urapidil and 8-OH-DPAT, induced a concentration-dependent relaxation in the porcine coronary and pulmonary artery rings with an intact endothelium (P<0.05). 5-HT and phenylephrine but not urapidil caused concentration-dependent contractions in human pulmonary artery rings. The present findings, while confirming that urapidil is a potent inhibitor of α1-adrenoceptor-induced contraction, do not support the role of 5-HT1A receptor activation in the control of the vascular tone of the different types of arteries tested in response to urapidil. In addition, they indicate that urapidil seems to preferentially target arteries with endothelial dysfunction.

  19. Role of 5-HT1 receptor subtypes in the modulation of pain and synaptic transmission in rat spinal superficial dorsal horn

    PubMed Central

    Jeong, Hyo-Jin; Mitchell, Vanessa A; Vaughan, Christopher W

    2012-01-01

    BACKGROUND AND PURPOSE 5-HT receptor agonists have variable nociceptive effects within the spinal cord. While there is some evidence for 5-HT1A spinally-mediated analgesia, the role of other 5-HT1 receptor subtypes remains unclear. In the present study, we examined the spinal actions of a range of 5-HT1 agonists, including sumatriptan, on acute pain, plus their effect on afferent-evoked synaptic transmission onto superficial dorsal horn neurons. EXPERIMENTAL APPROACH For in vivo experiments, 5-HT agonists were injected via chronically implanted spinal catheters to examine their effects in acute mechanical and thermal pain assays using a paw pressure analgesymeter and a Hargreave's device. For in vitro experiments, whole-cell patch-clamp recordings of primary afferent-evoked glutamatergic EPSC were made from lamina II neurons in rat lumbar spinal slices. KEY RESULTS Intrathecal (i.t.) delivery of the 5-HT1A agonist R ± 8-OH-DPAT (30–300 nmol) produced a dose-dependent thermal, but not mechanical, analgesia. Sumatriptan and the 5-HT1B, 5-HT1D, 5-HT1F agonists CP93129, PNU109291 and LY344864 (100 nmol) had no effect on either acute pain assay. R ± 8-OH-DPAT (1 µM) and sumatriptan (3 µM) both reduced the amplitude of the evoked EPSC. In contrast, CP93129, PNU109291 and LY344864 (0.3–3 µM) had no effect on the evoked EPSC. The actions of both R ± 8-OH-DPAT and sumatriptan were abolished by the 5-HT1A antagonist WAY100635 (3 µM). CONCLUSIONS AND IMPLICATIONS These findings indicate that the 5-HT1A receptor subtype predominantly mediates the acute antinociceptive and cellular actions of 5-HT1 ligands within the rat superficial dorsal horn. PMID:21950560

  20. 5-HT1A and 5-HT7 receptor crosstalk in the regulation of emotional memory: implications for effects of selective serotonin reuptake inhibitors.

    PubMed

    Eriksson, Therese M; Holst, Sarah; Stan, Tiberiu L; Hager, Torben; Sjögren, Benita; Ogren, Sven Öve; Svenningsson, Per; Stiedl, Oliver

    2012-11-01

    This study utilized pharmacological manipulations to analyze the role of direct and indirect activation of 5-HT(7) receptors (5-HT(7)Rs) in passive avoidance learning by assessing emotional memory in male C57BL/6J mice. Additionally, 5-HT(7)R binding affinity and 5-HT(7)R-mediated protein phosphorylation of downstream signaling targets were determined. Elevation of 5-HT by the selective serotonin reuptake inhibitor (SSRI) fluoxetine had no effect by itself, but facilitated emotional memory performance when combined with the 5-HT(1A)R antagonist NAD-299. This facilitation was blocked by the selective 5-HT(7)R antagonist SB269970, revealing excitatory effects of the SSRI via 5-HT(7)Rs. The enhanced memory retention by NAD-299 was blocked by SB269970, indicating that reduced activation of 5-HT(1A)Rs results in enhanced 5-HT stimulation of 5-HT(7)Rs. The putative 5-HT(7)R agonists LP-44 when administered systemically and AS19 when administered both systemically and into the dorsal hippocampus failed to facilitate memory. This finding is consistent with the low efficacy of LP-44 and AS19 to stimulate protein phosphorylation of 5-HT(7)R-activated signaling cascades. In contrast, increasing doses of the dual 5-HT(1A)R/5-HT(7)R agonist 8-OH-DPAT impaired memory, while co-administration with NAD-299 facilitated of emotional memory in a dose-dependent manner. This facilitation was blocked by SB269970 indicating 5-HT(7)R activation by 8-OH-DPAT. Dorsohippocampal infusion of 8-OH-DPAT impaired passive avoidance retention through hippocampal 5-HT(1A)R activation, while 5-HT(7)Rs appear to facilitate memory processes in a broader cortico-limbic network and not the hippocampus alone.

  1. Social instigation and aggression in postpartum female rats: role of 5-Ht1A and 5-Ht1B receptors in the dorsal raphé nucleus and prefrontal cortex

    PubMed Central

    da Veiga, Caroline Perinazzo; Miczek, Klaus A.; Lucion, Aldo Bolten

    2013-01-01

    Rationale 5-HT1A and 5-HT1B receptor agonists effectively reduce aggressive behavior in males that has been escalated by social instigation. Important sites of action for these drugs are the receptors in dorsal raphé nuclei (DRN) and the ventral–orbital prefrontal cortex (VO PFC). DRN and VO PFC areas are particularly relevant in the inhibitory control of escalated aggressive and impulsive behavior. Objectives The objectives of this study are to assess the anti-aggressive effects of 5-HT1A (8-OH-DPAT) and 5-HT1B (CP-93,129) receptor agonists microinjected into DRN and VO PFC, respectively, and to study the aggressive behavior in postpartum female Wistar rats using the social instigation protocol to increase aggression. Methods and Results 8-OH-DPAT (0.56 µg) in the DRN increased aggressive behavior in postpartum female rats. By contrast, CP-93,129 (1.0 µg) microinjected into VO PFC decreased the number of attack bites and lateral threats. 5-HT1A and 5-HT1B receptor agonists differed in their effects on non-aggressive activities, the former decreasing rearing and grooming and the latter increasing these acts. When 8-OH-DPAT was microinjected into DRN and CP-93,129 was microinjected into VO PFC in female rats at the same time, maternal aggression decreased. Specific participation of 5-HT1B receptors was verified by reversal of the anti-aggressive effects using the selective antagonist SB-224,289 (1.0 µg). Conclusions The decrease in maternal aggressive behavior after microinjections of 5-HT1B receptor agonists into the VO PFC and DRN of female postpartum rats that were instigated socially supports the hypothesis that activation of these receptors modulates high levels of aggression in a behaviorally specific manner, due to activation of 5-HT1B receptors at the soma and terminals. PMID:21107539

  2. Enhanced reactivity of 5-HT1A receptors in the rat dorsal periaqueductal gray matter after chronic treatment with fluoxetine and sertraline: evidence from the elevated T-maze.

    PubMed

    Zanoveli, Janaina Menezes; Nogueira, Regina Lúcia; Zangrossi, Hélio

    2007-03-01

    Behavioral evidence indicates that sensitization of 5-HT1A and 5-HT2A receptors in the dorsal periaqueductal gray (DPAG) may underlie the therapeutic effect of serotonin reuptake inhibitors (SRIs) in panic disorder. These results were obtained from studies using animal models that associate escape behavior with panic attacks, such as the elevated T-maze. In this test, chronic administration of the non-selective SRI imipramine enhances the inhibitory effect on escape caused by the intra-DPAG injection of the 5-HT1A receptor agonist 8-OH-DPAT. We here evaluated the generality of this finding by investigating the effect of chronic administration of two selective SRIs (SSRIs), fluoxetine and sertraline, on the reactivity of the rat DPAG 5-HT1A receptors. The results showed that both SSRIs inhibited escape behavior in the elevated T-maze, suggestive of a panicolytic-like effect. Whereas intra-DPAG injection of a low dose of 8-OH-DPAT (0.4nmol) had no effect on escape in control animals, it significantly enhanced the inhibitory effect caused by the SSRIs on this response. Microinjection of 8-OH-DPAT in SSRI-treated rats also inhibited the acquisition of inhibitory avoidance, another defensive response measured by the elevated T-maze. The results indicate that chronic administration of fluoxetine and sertraline sensitizes 5-HT1A receptors in the DPAG. Overall, they support the view that facilitation of 5-HT1A receptor-mediated neurotransmission in the DPAG is implicated in the therapeutic effect of SRIs on panic disorder.

  3. Interactions Between Corticotropin-Releasing Factor and the Serotonin 1A Receptor System on Acoustic Startle Amplitude and Prepulse Inhibition of the Startle Response in Two Rat Strains

    PubMed Central

    Conti, Lisa H.

    2011-01-01

    Both the neuropeptide, corticotropin-releasing factor (CRF) and the serotonin 1A (5-HT1A) receptor systems have been implicated in anxiety disorders and there is evidence that the two systems interact with each other to affect behavior. Both systems have individually been shown to affect prepulse inhibition (PPI) of the acoustic startle response. PPI is a form of sensorimotor gating that is reduced in patients with anxiety disorders including post-traumatic stress and panic disorder. Here, we examined whether the two systems interact or counteract each other to affect acoustic startle amplitude, PPI and habituation of the startle response. In experiment 1, Brown Norway (BN) and Wistar-Kyoto (WKY) rats were administered ether an intraperitoneal (IP) injection of saline or the 5-HT1A receptor agonist, 8-OH-DPAT 10 min prior to receiving an intracerebroventricular (ICV) infusion of either saline or CRF (0.3 µg). In a second experiment, rats were administered either an IP injection of saline or the 5-HT1A receptor antagonist, WAY 100,635 10 min prior to receiving an ICV infusion of saline or CRF. Thirty min after the ICV infusion, the startle response and PPI were assessed. As we have previously shown, the dose of CRF used in these experiments reduced PPI in BN rats and had no effect on PPI in WKY rats. Administration of 8-OH-DPAT alone had no effect on PPI in either rat strain when the data from the two strains were examined separately. Administration of 8-OHDPAT added to the effect of CRF in BN rats, and the combination of 8-OH-DPAT and CRF significantly reduced PPI in WKY rats. CRF alone had no effect on baseline startle amplitude in either rat strain, but CRF enhanced the 8-OH-DPAT-induced increase in startle in both strains. Administration of WAY 100,635 did not affect the CRF-induced change in PPI and there were no interactions between CRF and WAY 100,635 on baseline startle. The results suggest that activation of the 5-HT1A receptor can potentiate the effect of

  4. Brief constant light accelerates serotonergic re-entrainment to large shifts of the daily light/dark cycle.

    PubMed

    Kaur, G; Thind, R; Glass, J D

    2009-04-10

    Brief ( approximately 2 day) constant light exposure (LL(b)) in hamsters dramatically enhances circadian phase-resetting induced by the 5-HT receptor agonist, (+/-)-2-dipropyl-amino-8-hydroxyl-1,2,3,4-tetrahydronapthalene (8-OH-DPAT) and other nonphotic stimuli. The present study was undertaken to determine if LL(b) can also amplify phase-resetting responses to endogenous 5-HT and accelerate re-entrainment to large-magnitude advance and delay shifts of the light/dark (LD) cycle. First, central serotonergic activity was increased by i.p. injection of L-tryptophan+/-the 5-HT reuptake inhibitor fluoxetine. Hamsters under LD or exposed to LL(b) received vehicle or drugs during the early morning, and phase-shifts of the locomotor activity rhythm were measured after release to constant darkness. Neither drug phase-shifted animals not exposed to LL(b) (P>0.5 vs. vehicle); however in animals receiving LL(b,)L-tryptophan with and without fluoxetine produced large phase-advance shifts (means=2.5+/-0.4 h and 2.6+/-0.2 h, respectively; both P<0.035 vs. vehicle). Next, the effects of LL(b) combined with 8-OH-DPAT or L-tryptophan+fluoxetine on serotonergic re-entrainment to 10 h phase-advance and phase-delay shifts of the LD cycle were assessed. In groups not exposed to LL(b), vehicle controls re-entrained slowly to the advance and delay shifts (means=16+/-1 and 24+/-4 days, respectively), but those treated with 8-OH-DPAT re-entrained faster (means=11+/-2 and 9+/-2 days, respectively; both P<0.05 vs. vehicle). In groups exposed to LL(b), vehicle controls re-entrained slowly to the advance and delay shifts (means=15+/-2 and 25+/-3 days, respectively); however those receiving 8-OH-DPAT rapidly re-entrained to the delay and advance shifts, with the majority (75%) requiring only 1-2 days (means=2+/-1 and 4+/-2 days, respectively; both P<0.05 vs. vehicle). Animals exposed to LL(b) and treated with L-tryptophan+fluoxetine also exhibited accelerated re-entrainment to a 10 h advance

  5. Differential regulation of serotonin-1A receptor-stimulated [35S]GTP gamma S binding in the dorsal raphe nucleus by citalopram and escitalopram.

    PubMed

    Rossi, Dania V; Burke, Teresa F; Hensler, Julie G

    2008-03-31

    The effect of chronic citalopram or escitalopram administration on 5-HT1A receptor function in the dorsal raphe nucleus was determined by measuring [35S]GTP gamma S binding stimulated by the 5-HT1A receptor agonist (R)-(+)-8-OH-DPAT (1nM-10 microM). Although chronic administration of citalopram or escitalopram has been shown to desensitize somatodendritic 5-HT1A autoreceptors, we found that escitalopram treatment decreased the efficacy of 5-HT1A receptors to activate G proteins, whereas citalopram treatment did not. The binding of [3H]8-OH-DPAT to the coupled, high affinity agonist state of the receptor was not altered by either treatment. Interestingly, escitalopram administration resulted in greater occupancy of serotonin transporter sites as measured by the inhibition of [3H]cyanoimipramine binding. As the binding and action of escitalopram is limited by the inactive enantiomer R-citalopram present in racemic citalopram, we propose that the regulation of 5-HT1A receptor function in the dorsal raphe nucleus at the level of receptor-G protein interaction may be a result of greater inhibition of the serotonin transporter by escitalopram.

  6. Roles of hippocampal GABA(A) and muscarinic receptors in consolidation of context memory and context-shock association in contextual fear conditioning: a double dissociation study.

    PubMed

    Chang, Shih-Dar; Liang, K C

    2012-07-01

    Contextual fear conditioning involves forming a context representation and associating it to a shock, both of which involved the dorsal hippocampus (DH) according to our recent findings. This study tested further whether the two processes may rely on different neurotransmitter systems in the DH. Male Wistar rats with cannula implanted into the DH were subjected to a two-phase training paradigm of contextual fear conditioning to separate context learning from context-shock association in two consecutive days. Immediately after each training phase, different groups of rats received bilateral intra-DH infusion of the GABA(A) agonist muscimol, 5HT(1A) agonist 8-OH-DPAT, NMDA antagonist APV or muscarinic antagonist scopolamine at various doses. On the third day, freezing behavior was tested in the conditioning context. Results showed that intra-DH infusion of muscimol impaired conditioned freezing only if it was given after context learning. In contrast, scopolamine impaired conditioned freezing only if it was given after context-shock training. Posttraining infusion of 8-OH-DPAT or APV had no effect on conditioned freezing when the drug was given at either phase. These results showed double dissociation for the hippocampal GABAergic and cholinergic systems in memory consolidation of contextual fear conditioning: forming context memory required deactivation of the GABA(A) receptors, while forming context-shock memory involved activation of the muscarinic receptors.

  7. Atypical antipsychotics suppress production of proinflammatory cytokines and up-regulate interleukin-10 in lipopolysaccharide-treated mice.

    PubMed

    Sugino, Haruhiko; Futamura, Takashi; Mitsumoto, Yasuhide; Maeda, Kenji; Marunaka, Yoshinori

    2009-03-17

    There is considerable evidence that schizophrenia is associated with immune system dysregulation. For example, blood and cerebrospinal fluid (CSF) levels of proinflammatory cytokines are significantly increased in schizophrenic patients, and their normalization correlates with improvement in psychotic symptoms. In fact, typical and atypical antipsychotics are reported to modulate immune function in in vitro and in vivo studies. In the present study, we examined the anti-inflammatory effect of antipsychotics, clozapine, olanzapine, risperidone and haloperidol, on serum cytokine levels in lipopolysaccharide (LPS)-treated mice. Atypical antipsychotics, such as clozapine, olanzapine and risperidone, but not haloperidol, suppressed tumor necrosis factor (TNF)-alpha and interleukin (IL)-6, and up-regulated IL-10. Moreover, only clozapine, robustly increased the serum levels of IL-10. Clozapine reproduced its anti-inflammatory feature in polyinsinic-polycytidylic acid sodium salt (Poly[I:C])-induced inflammation. Thus, the anti-inflammatory effect of clozapine would adapt to inflammation induced by some varieties of antigens. Several receptor ligands, such as 8-OH-DPAT, ketanserin, prazosin and scopolamine, were also examined as to their anti-inflammatory effects on serum cytokine levels in LPS-treated mice. Ketanserin and prazosin, but not 8-OH-DPAT nor scopolamine, behaved similarly to atypical antipsychotics. However, the remarkable increase of serum IL-10 level observed in clozapine was not detected in ketanserin and prazosin. These results suggest the unique efficacy of atypical antipsychotics in the suppression of proinflammatory cytokines, and the increase of anti-inflammatory cytokine, IL-10.

  8. Role of Serotonergic System on Modulation of Depressogenic-Like Effects of Silymarine

    PubMed Central

    Yaghmaei, Parichehr; Oryan, Shahrbanoo; Mohammadi, Khadijeh; Solati, Jalal

    2012-01-01

    In the present study, we have investigated the effects of silymarine on depression and the possible role of serotonergic system in these effects. The rats were anesthetized intraperitoneally with ketamine hydrochloride and placed in a Stoelting stereotaxic instrument. A stainless steel guide cannula (22-gauge) was implanted in the third ventricular region. The third ventricular region was infused by means of an internal cannula (27-gauge), terminated 1 mm below the tip of the guide cannula. Forced swimming test was used for evaluating the depression. The results obtained from this study showed that oral administration of silymarin (35, 70, 140 and 280 mg/rat) for two weeks increased the immobility time in forced swimming test, indicating an increase in depression level of the treated rats. Intra-third-ventricle (Intra-TV) infusion of 5HT1A receptor agonist 8-OH-DPAT (25 and 10 ng/rat) decreased the immobility time indicating an anti-depression effect, while injection of 5HT1A receptor antagonist NAN190 (0.25, 0.5 and 1 μg/rat) had no significant effect on immobility time. An effective dose of 8-OH-DPAT (10 ng/rat) co-administered with silymarin (140 and 280 mg/rat) decreased the depressogenic effects of silymarin. These results showed that the depressogenic effects of silymarin may be modulated via 5HT1A receptor of serotonin. PMID:24250456

  9. Activation of the serotonergic 5-HT1A receptor in the paraventricular nucleus of the hypothalamus inhibits water intake and increases urinary excretion in water-deprived rats.

    PubMed

    de Souza Villa, Patrícia; Menani, José Vanderlei; de Arruda Camargo, Gabriela Maria Pavan; de Arruda Camargo, Luiz Antônio; Saad, Wilson Abrão

    2008-10-09

    The paraventricular nucleus (PVN) may be considered as a dynamic mosaic of chemically-specified subgroups of neurons. 5-HT(1A) is one of the prime receptors identified and there is expressed throughout all magnocellular regions of the PVN. Several reports have demonstrated that a subpopulation of the magnocellular neurons expressing 5-HT(1A) receptors are oxytocin (OT) neurons and activation of 5-HT(1A) receptors in the PVN increases the plasma OT. Increasing evidence shows that OT inhibits water intake and increases urinary excretion in rats. The aim of this study was to investigate the role of serotonergic 5-HT(1A) receptors in the lateral-medial posterior magnocellular region of the PVN in the water intake and diuresis induced by 24 h of water deprivation. Cannulae were implanted in the PVN of rats. 5-HT injections in the PVN reduced water intake and increased urinary excretion. 8-OH-DPAT (a 5-HT(1A) agonist) injections blocked the water intake and increased urinary output in all the periods of the observation. pMPPF (a 5-HT(1A) antagonist) injected bilaterally before the 8-OH-DPAT blocked its inhibitory effect on water intake and its diuretic effect. We suggest that antidipsogenic and diuretic responses seem to be mediated via 5-HT(1A) receptors of the lateral-medial posterior magnocellular region of the PVN in water-deprived rats.

  10. Role of serotonin 1A receptors in the median raphe nucleus on the behavioral consequences of forced swim stress.

    PubMed

    Almeida, P V G; Trovo, M C; Tokumoto, A M; Pereira, A C; Padovan, C M

    2013-12-01

    Despite the intense research on the neurobiology of stress, the role of serotonin (5-HT)1A receptors still remains to be elucidated. In the hippocampus, post-synaptic 5-HT1A receptors activation induces anxiolytic effects in animals previously exposed to stressful situations. However, little is known about somatodendritic 5-HT1A receptors in the median raphe nucleus (MRN). Therefore, the aim of this study was to investigate the role of 5-HT1A receptors located in the MRN in rats exposed to forced swim stress. After recovering from surgery, rats were forced to swim for 15 min in a cylinder. Intra-MRN injections of saline, 8-OH-DPAT (3 nmol/0.2 µL) and/or WAY-100635 (0.3 nmol/0.2 µL) were performed immediately before or after pre-exposure or 24 h later (immediately before test). Non-stressed rats received the same treatment 24 h or 10 min before test. Our data showed that 8-OH-DPAT increased latency to display immobility while decreasing time spent immobile in almost all experimental conditions. These effects were not prevented by previous treatment with WAY-100635. No effects of different treatments were described in non-stressed animals. Taken together, our data suggest that in addition to activation of 5-HT1A, 5-HT7 receptors may also be involved in the behavioural consequences of exposure to swim stress.

  11. Functional MRI to assess alterations of functional networks in response to pharmacological or genetic manipulations of the serotonergic system in mice.

    PubMed

    Razoux, Florence; Baltes, Christof; Mueggler, Thomas; Seuwen, Aline; Russig, Holger; Mansuy, Isabelle; Rudin, Markus

    2013-07-01

    Imaging methods that enable the investigation of functional networks both in human and animal brain provide important insights into mechanisms underlying pathologies including psychiatric disorders. Since the serotonergic receptor 1A (5-HT(1A)-R) has been strongly implicated in the pathophysiology of depressive and anxiety disorders, as well as in the action of antidepressant drugs, we investigated brain connectivity related to the 5-HT(1A)-R system by use of pharmacological functional magnetic resonance imaging in mice. We characterized functional connectivity elicited by activation of 5-HT(1A)-R and investigated how pharmacological and genetic manipulations of its function may modulate the evoked connectivity. Functional connectivity elicited by administration of the 5-HT(1A)-R agonist 8-OH-DPAT can be described by networks characterized by small-world attributes with nodes displaying highly concerted response patterns. Circuits identified comprised the brain structures known to be involved in stress-related disorders (e.g. prefrontal cortex, amygdala and hippocampus). The results also highlight the dorsomedial thalamus, a structure associated with fear processing, as a hub of the 5-HT(1A)-R functional network. Administration of a specific 5-HT(1A)-R antagonist or use of heterozygous 5-HT(1A)-R knockout mice significantly reduced functional connectivity elicited by 8-OH-DPAT. Whole brain functional connectivity analysis constitutes an attractive tool to characterize impairments in neurotransmission and the efficacy of pharmacological treatment in a comprehensive manner.

  12. Do imipramine and dihydroergosine possess two components - one stimulating 5-HT sub 1 and the other inhibiting 5-HT sub 2 receptors

    SciTech Connect

    Pericic, D.; Mueck-Seler, D. )

    1990-01-01

    The mechanisms by which imipramine and dihydroergosine stimulate the 5-HT syndrome in rats and inhibit the head-twitch response in rats and mice were studied. Imipramine- and dihydroergosine-included stimulation of the 5-HT syndrome was inhibited stereoselectively by propranolol, a high affinity ligand for 5-HT{sub 1} receptor sites, but not by ritanserin, a specific 5-HT{sub 2} receptor antagonist. (-) -Propranolol potentiated the inhibitory effect of imipramine, but not of dihydroergosine on the head-twitch response, while ritanserin was without effect. As expected, 8-OH-DPAT, a selective 5-HT{sub 1A} receptor agonist, stimulated, and 5-HT{sub 1B} agonists CGS 12066B and 1-(trifluoromethylphenyl) piperazine (TFMPP) failed to stimulate the 5-HT syndrome induced in rats by pargyline and 5-HTP administration. A higher dose of ritanserin inhibited the syndrome. While 8-OH-DPAT alone produced all behavioral components of the 5-HT syndrome, dihydroergosine or imipramine alone even at very high doses never produced tremor or a more intensive forepaw padding as seen when these drugs were given in combination with pargyline and 5-HTP. A single administration of (-)-propranolol also inhibited the head-twitch response. This effect lasted in mice longer that after ritanserin administration. In in vitro experiments dihydroergosine expressed approximately twenty-fold higher affinity for {sup 3}H-ketanserin binding sites than imipramine.

  13. [Effect of domestication of the silver fox on the main enzymes of serotonin metabolism and serotonin receptors].

    PubMed

    Popova, N K; Kulikov, A V; Avgustinovich, D F; Voĭtenko, N N; Trut, L N

    1997-03-01

    In silver foxes significant alterations in the activities of basic enzymes of neurotransmitter serotonin metabolism as well as in the densities of receptors caused by selection for the absence of the aggressive defensive reaction to man were demonstrated. In the midbrain and hypothalamus of animals selected for the absence of aggressive behavior, the activity of tryptophan hydroxylase, the key enzyme of serotonin biosynthesis, was found to be remarkably higher than in animals selected for highly aggressive behavior. Domesticated animals were characterized by low activity of the main enzyme of serotonin catabolism, monoamine oxidase type A, increased Michaelis constant km, and an unchanged maximum reaction rate (Vmax). No changes in the specific binding of [3H]-ketanserin and [3H]-8-OH-DPAT in the frontal cortex of domesticated foxes were revealed; however, in the hypothalamus, the low values of Bmax for the [3H]-8-OH-DPAT specific binding were observed, indicating the decreased density of the 5-HT1A receptors. It is assumed that the transformation of a wild aggressive animal into a domesticated one taking place during directional selection is caused by hereditary alterations favored by artificial selection in the activity of the main enzymes of serotonin metabolism and serotonin receptors.

  14. Alcohol-heightened aggression in mice: attenuation by 5-HT1A receptor agonists.

    PubMed

    Miczek, K A; Hussain, S; Faccidomo, S

    1998-09-01

    One of the critical mechanisms by which alcohol heightens aggression involves forebrain serotonin (5-HT) systems, possibly via actions on 5-HT1A receptors. The present experiments tested the hypothesis that activating 5-HT1A receptors by selective agonists will block the aggression-heightening effects of ethanol. Initially, the selective antagonist WAY 100635 was used to assess whether or not the changes in aggressive behavior after treatment with 8-OH-DPAT and flesinoxan result from action at the 5-HT1A receptors. Resident male CFW mice engaged in aggressive behavior (i.e. attack bites, sideways threats, tail rattle) during 5-min confrontations with a group-housed intruder male. Quantitative analysis of the behavioral repertoire revealed systematic reductions in all salient elements of aggressive behavior after treatment with 8-OH-DPAT (0.1-0.3 mg/kg, i.p.) or flesinoxan (0.1-1.0 mg/kg, i.p.). The 5-HT1A agonists also reduced motor activities such as walking, rearing and grooming, although to a lesser degree. Pretreatment with the antagonist WAY 100635 (0.1 mg/kg, i.p.) shifted the agonist dose-effect curves for behavioral effects to the right. In a further experiment, oral ethanol (1.0 g/kg, p.o.) increased the frequency of attacks in excess of 2 SD from their mean vehicle level of attacks in 19 out of 76 resident mice. Low doses of 8-OH-DPAT (0.03-0.3 mg/kg) and flesinoxan (0.1, 0.3, 0.6 mg/kg), given before the ethanol treatment, attenuated the alcohol-heightened aggression in a dose-dependent fashion. By contrast, these low 5-HT1A agonist doses affected motor activity in ethanol-treated resident mice to a lesser degree, suggesting behavioral specificity of these anti-aggressive effects. The current results support the hypothesized significant role of 5-HT1A receptors in the aggression-heightening effects of alcohol. If these effects are in fact due to action at somatodendritic 5-HT1A autoreceptors, then the anti-aggressive effects would be associated with

  15. On the role of brain 5-HT7 receptor in the mechanism of hypothermia: comparison with hypothermia mediated via 5-HT1A and 5-HT3 receptor.

    PubMed

    Naumenko, Vladimir S; Kondaurova, Elena M; Popova, Nina K

    2011-12-01

    Intracerebroventricular administration of selective agonist of serotonin 5-HT(7) receptor LP44 (4-[2-(methylthio)phenyl]-N-(1,2,3,4-tetrahydro-1-naphthalenyl)-1-pyperasinehexanamide hydrochloride; 10.3, 20.5 or 41.0 nmol) produced considerable hypothermic response in CBA/Lac mice. LP44-induced (20.5 nmol) hypothermia was significantly attenuated by the selective 5-HT(7) receptor antagonist SB 269970 (16.1 fmol, i.c.v.) pretreatment. At the same time, intraperitoneal administration of LP44 in a wide range of doses 1.0, 2.0 or 10.0 mg/kg (2.0, 4.0, 20.0 μmol/kg) did not cause considerable hypothermic response. These findings indicate the implication of central, rather than peripheral 5-HT(7) receptors in the regulation of hypothermia. The comparison of LP44-induced (20.5 nmol) hypothermic reaction in eight inbred mouse strains (DBA/2J, CBA/Lac, C57BL/6, BALB/c, ICR, AKR/J, C3H and Asn) was performed and a significant effect of genotype was found. In the same eight mouse strains, functional activity of 5-HT(1A) and 5-HT(3) receptors was studied. The comparison of hypothermic responses produced by 5-HT(7) receptor agonist LP44 (20.5 nmol, i.c.v.) and 5-HT(1A) receptor agonist 8-OH-DPAT 1.0 mg/kg, i.p. (3.0 μmol/kg), 5-HT(3) receptor agonist m-CPBG (40.0 nmol, i.c.v.) did not reveal considerable interstrain correlations between 5-HT(7) and 5-HT(1A) or 5-HT(3) receptor-induced hypothermia. The selective 5-HT(7) receptor antagonist SB 269970 (16.1 fmol, i.c.v.) failed to attenuate the hypothermic effect of 8-OH-DPAT 1.0 mg/kg, i.p. (3.0 μmol/kg) and m-CPBG (40.0 nmol, i.c.v.) indicating that the brain 5-HT(7) receptor is not involved in the hypothermic effects of 8-OH-DPAT or m-CPBG. The obtained results suggest that the central 5-HT(7) receptor plays an essential role in the mediation of thermoregulation independent of 5-HT(1A) and 5-HT(3) receptors.

  16. Serotonin-mediated central fatigue underlies increased endurance capacity in mice from lines selectively bred for high voluntary wheel running.

    PubMed

    Claghorn, Gerald C; Fonseca, Ivana A T; Thompson, Zoe; Barber, Curtis; Garland, Theodore

    2016-07-01

    Serotonin (5-hydroxytryptamine; 5-HT) is implicated in central fatigue, and 5-HT1A pharmaceuticals are known to influence locomotor endurance in both rodents and humans. We studied the effects of a 5-HT1A agonist and antagonist on both forced and voluntary exercise in the same set of mice. This cohort of mice was taken from 4 replicate lines of mice that have been selectively bred for high levels of voluntary wheel running (HR) as compared with 4 non-selected control (C) lines. HR mice run voluntarily on wheels about 3× as many revolutions per day as compared with C, and have greater endurance during forced treadmill exercise. We hypothesized that drugs targeting serotonin receptors would have differential effects on locomotor behavior of HR and C mice. Subcutaneous injections of a 5-HT1A antagonist (WAY-100,635), a combination of 5-HT1A agonist and a 5-HT1A/1B partial agonist (8-OH-DPAT+pindolol), or physiological saline were given to separate groups of male mice before the start of each of three treadmill trials. The same manipulations were used later during voluntary wheel running on three separate nights. WAY-100,635 decreased treadmill endurance in HR but not C mice (dose by linetype interaction, P=0.0014). 8-OH-DPAT+pindolol affected treadmill endurance (P<0.0001) in a dose-dependent manner, with no dose by linetype interaction. Wheel running was reduced in HR but not C mice at the highest dose of 8-OH-DPAT+pindolol (dose by linetype, P=0.0221), but was not affected by WAY-100,635 treatment. These results provide further evidence that serotonin signaling is an important determinant of performance during both forced and voluntary exercise. Although the elevated wheel running of HR mice does not appear related to alterations in serotonin signaling, their enhanced endurance capacity does. More generally, our results indicate that both forced and voluntary exercise can be affected by an intervention that acts (primarily) centrally.

  17. Hippocampal EEG and Unit Activity Responses to Modulation of Serotonergic Median Raphe Neurons in the Freely Behaving Rat

    PubMed Central

    Nitz, Douglas A.; McNaughton, Bruce L.

    1999-01-01

    Hippocampal EEG, GABAergic interneurons, and principal cells were recorded simultaneously as rats foraged within one of three environments both before and after modulation of serotonergic inputs to the hippocampus. Median raphe microinjections of the 5-HT1a receptor agonist 8-OH-DPAT were made to produce inhibition of serotonergic neurons in this region. Such microinjections produced behavioral arousal and increases in the amplitude of hippocampal EEG theta. Consistent with the pattern of serotonergic innervation of the hippocampus, the GABAergic interneuron population was affected differentially by the microinjections. Principal cells were generally unaffected by the manipulation and maintained robust spatial firing correlates within the foraging environment. The results provide basic data on the relationship between serotonergic median raphe neurons and hippocampal activity in a behaving animal. The data suggest that behavioral responses to manipulation of the serotonergic system are mediated by brain regions other than the hippocampus or are mediated through changes in the activity of hippocampal interneurons. PMID:10327240

  18. Autoradiographic evaluation of [3H]CUMI-101, a novel, selective 5-HT1AR ligand in human and baboon brain

    PubMed Central

    Dileep Kumar, J. S.; Parsey, Ramin V.; Kassir, Suham A.; Majo, Vattoly J.; Milak, Matthew S.; Prabhakaran, Jaya; Underwood, Mark D.; Mann, J. John; Arango, Victoria

    2014-01-01

    [11C]CUMI-101 is the first selective serotonin receptor (5-HT1AR) partial agonist radiotracer for positron emission tomography (PET) tested in vivo in nonhuman primates and humans. We evaluated specific binding of [3H]CUMI-101 by quantitative autoradiography studies in postmortem baboon and human brain sections using the 5- HT1AR antagonist WAY100635 as a displacer. The regional and laminar distributions of [3H]CUMI-101 binding in baboon and human brain sections matched the known distribution of [3H]8-OH-DPAT and [3H]WAY100635. Prazosin did not measurably displace [3H]CUMI-101 binding in baboon or human brain sections, thereby ruling out [3H]CUMI-101 binding to α1-adrenergic receptors. This study demonstrates that [11C]CUMI-101 is a selective 5-HT1AR ligand for in vivo and in vitro studies in baboon and human brain. PMID:23454434

  19. Serotonergic mechanisms in emesis

    NASA Technical Reports Server (NTRS)

    Lucot, J. B.; Crampton, G. H.

    1988-01-01

    The observation that the cerebrospinal fluid of cats which are susceptible to motion sickness contained lower baseline levels of 5-hydroxyindoleacetic acid, among other constituents, led to the hypothesis that serotonin inhibits emesis. The hypothesis was tested by administration of the serotonin-1A agonists buspirone and 8-OH-DPAT before motion testing in cats susceptible to motion sickness. Both drugs blocked motion sickness in a dose-dependent fashion. To determine if these drugs blocked emesis elicited by other stimuli, they were administered before subcutaneous administration of the alpha-2 noradrenergic agonist, xylazine. Both drugs also blocked xylazine-induced emesis. It was concluded that the stimulation of serotonin-1A receptors inhibits emesis elicited by the two stimuli and that this mechanism may exert a general antiemetic effect.

  20. Pharmacological profile of a potential anxiolytic: AP159, a new benzothieno-pyridine derivative.

    PubMed

    Nagatani, T; Yamamoto, T; Takao, K; Hashimoto, S; Kasahara, K; Sugihara, T; Ueki, S

    1991-01-01

    AP159 [N-cyclohexyl-1,2,3,4-tetrahydrobenzo(b)thieno(2,3c)pyridine]-3- carboamide,hydrochloride) showed clear anti-conflict activity in rats in the absence of effects on muscle relaxation, potentiation of anesthesia (in mice) or anticonvulsant activity (in mice). This anti-conflict effect was antagonized by treatment with Ro15-1788. By contrast with the deficits produced by diazepam, AP159 did not impair passive avoidance. The latter drug also improved scopolamine-induced amnesia in the same task. AP159 did not inhibit 3H-flunitrazepam binding, but potently inhibited 3H-8OH-DPAT binding. This compound increased serotonin and 5HIAA content of the midbrain raphe nuclei and of the amygdala centralis. AP159 has been shown to be a novel non-BZP anxiolytic agent with no side effects in laboratory animals; it could be a clinically effective anxiolytic agent.

  1. Serotonergic agonists behave as partial agonists at the dopamine D2 receptor.

    PubMed

    Rinken, A; Ferré, S; Terasmaa, A; Owman, C; Fuxe, K

    1999-02-25

    RAT dopamine D2short receptors expressed in CHO cells were characterized by activation of [35S]GTPgammaS binding. There were no significant differences between the maximal effects seen in activation of [35S]GTPgammaS binding caused by dopaminergic agonists, but the effects of 5-HT, 8OH-DPAT and 5-methoxytryptamine amounted to 47 +/- 7%, 43 +/- 5% and 70 +/- 7% of the dopamine effect, respectively. The dopaminergic antagonist (+)butaclamol inhibited activations of both types of ligands with equal potency (pA2 = 8.9 +/- 0.1), indicating that only one type of receptor is involved. In competition with [3H]raclopride binding, dopaminergic agonists showed 53 +/- 2% of the binding sites in the GTP-dependent high-affinity state, whereas 5-HT showed only 20 +/- 3%. Taken together, the results indicate that serotonergic agonists behave as typical partial agonists for D2 receptors with potential antiparkinsonian activity.

  2. Food intake inhibition in rainbow trout induced by activation of serotonin 5-HT2C receptors is associated with increases in POMC, CART and CRF mRNA abundance in hypothalamus.

    PubMed

    Pérez-Maceira, Jorge J; Otero-Rodiño, Cristina; Mancebo, María J; Soengas, José L; Aldegunde, Manuel

    2016-04-01

    In rainbow trout, the food intake inhibition induced by serotonin occurs through 5-HT2C and 5-HT1A receptors, though the mechanisms involved are still unknown. Therefore, we assessed if a direct stimulation of 5-HT2C and 5-HT1A serotonin receptors (resulting in decreased food intake in rainbow trout), affects gene expression of neuropeptides involved in the control of food intake, such as pro-opiomelanocortin (POMC), cocaine- and amphetamine-regulated transcript (CART), corticotrophin releasing factor (CRF), and agouti-related peptide (AgRP). In a first set of experiments, the injection of the 5-HT2C receptor agonists MK212 (60 μg kg(-1) icv) and WAY 161503 (1 mg kg(-1) ip), and of the 5-HT1A receptor agonist 8-OH-DPAT (1 mg kg(-1) ip and 30 μg kg(-1) icv) induced food intake inhibition. In a second set of experiments, we observed that the injection of MK212 or WAY 161503 (1 and 3 mg kg(-1)) significantly increased hypothalamic POMC mRNA abundance. CART mRNA abundance in hypothalamus was enhanced by treatment with MK212 and unaffected by WAY 161503. The administration of the 5-HT1A receptor agonist 8-OH-DPAT did not induce any significant variation in the hypothalamic POMC or CART mRNA levels. CRF mRNA abundance was only affected by MK212 that increased hypothalamic values. Finally, hypothalamic AgRP mRNA abundance was only evaluated with the agonist 5-HT2C MK212 resulting in no significant effects. The results show that the reduction in food intake mediated by 5-HT2C receptors is associated with increases in hypothalamic POMC, CART and CRF mRNA abundance.

  3. Serotonin and the mammalian circadian system: II. Phase-shifting rat behavioral rhythms with serotonergic agonists.

    PubMed

    Edgar, D M; Miller, J D; Prosser, R A; Dean, R R; Dement, W C

    1993-01-01

    The suprachiasmatic nuclei (SCN) receive primary afferents from the median and dorsal raphe, but the role of these projections in circadian timekeeping is poorly understood. Studies of the SCN in vitro suggest that quipazine, a general serotonin (5-HT) receptor agonist, can produce circadian time-dependent phase advances and phase delays in circadian rhythms of neuronal activity. The present study addresses whether quipazine and the selective 5-HT1A receptor agonist 8-OH-DPAT are similarly effective in vivo. Drinking and wheel-running patterns of male Wistar rats individually housed in constant darkness were monitored before and after subcutaneous administration of quipazine (5-10 mg/kg) at either circadian time (CT) 6 or CT 18, with and without running wheels available. Dose-dependent phase advances (20-180 min) were produced at CT 6. Significant phase shifts were not observed at CT 18. CT 6 quipazine-treated animals also showed a sustained and significant shortening of rhythm period (tau) following treatment (-0.28 hr; p < 0.002). tau shortening was inconsistently observed in CT 18 quipazine-treated rats. Neither quipazine-induced phase shifts nor tau effects were dependent on wheel-running activity per se. 8-OH-DPAT delivered via intracerebral ventricular treatment into the third ventricle (5 microliters at 100 microM in saline) produced slightly smaller phase advances (20-90 min) at CT 6, but did not produce phase delays at CT 18 or changes in tau. These findings support in vitro evidence that 5-HT-ergic agonists can phase-shift the circadian pacemaker.

  4. The effect of natural clinoptilolite on the serotonergic receptors in the brain of mice with mammary carcinoma.

    PubMed

    Mück-Seler, Dorotea; Pivac, Nela

    2003-09-05

    The ex vivo effect of tribomechanically micronized zeolite (MZ) on the binding of 3H-8-OH-DPAT to 5-HT(1A) and 3H-5-HT to 5-HT(1B) receptors was investigated in the brain of nontumorous (control) and mammary carcinoma bearing female mice. During 14 and 28 days mice were fed with standard food, standard food supplemented with 25% of MZ, or standard food supplemented with 25% of non tribomechanically micronized zeolite (non-MZ). A reduced binding of 3H-8-OH-DPAT to 5-HT(1A) receptors in mammary carcinoma bearing mice was found when compared to control mice fed with standard food for 28 days, suggesting a time dependent alteration of 5-HT(1A) receptors in mammary carcinoma. The addition of MZ for 28 days in these mice abolished the decrease in 5-HT(1A) receptors binding, indicating a possible beneficial effect of MZ, at least on 5-HT(1A) receptors in mammary carcinoma bearing mice. The preliminary data show that MZ administered as a food supplement (25%) for 14 days induced a transient decrease in the binding of 3H-5-HT to brain 5-HT(1B) receptors only in control, but not in tumor-bearing mice, that disappeared after 28 days of MZ-supplemented food administration. The mechanism of the indirect action of MZ on the brain serotonergic receptors might be achieved by the alterations in the electrolytes balance, and/or by the regulation of the immune system.

  5. Pharmacological modulation of amphetamine-induced dyskinesia in transplanted hemi-parkinsonian rats.

    PubMed

    Smith, Gaynor A; Breger, Ludivine S; Lane, Emma L; Dunnett, Stephen B

    2012-10-01

    Foetal cell transplantation in patients with Parkinson's disease can induce motor complications independent of L-DOPA administration, known as graft-induced dyskinesia. In the 6-OHDA lesioned rat model of Parkinson's disease, post-transplantation abnormal movements can develop in response to an amphetamine challenge, a behaviour which is used to model graft-induced dyskinesia. Although L-DOPA-induced dyskinesia has been well characterised pharmacologically, we lack knowledge on the modulation of post-transplantation amphetamine-induced dyskinesia which may shed light on the mechanisms underlying graft-induced dyskinesia. We assessed a series of drugs effective at reducing L-DOPA-induced dyskinesia against post-transplantation amphetamine-induced dyskinesia. Agents include: dopaminergic antagonists (D₁: CP94253; D₂: SCH-22390; D₃: nafadotride), serotonergic agonists (5-HT(1A): 8-OH-DPAT; 5-HT(1B): CP94253), opioid antagonist (μ: naloxone), cannabinoid agonist (CB₁: WIN55, 212-2), adrenergic antagonist (α₁ and α₂: yohimbine) and glutamatergic antagonists (NMDA: amantadine and MK-801; mGluR5: MTEP; AMPA: IEM1460). Abnormal involuntary movements in response to amphetamine were decreased by SCH-22390, raclopride, CP94253 and 8-OH-DPAT, yet were unaltered by naloxone, WIN55, 212-2, yohimbine, amantadine, MTEP and IEM1460. Unusually, MK-801 increased the appearance of amphetamine-induced dyskinesia. The results suggest that dopaminergic, serotoninergic and glutamatergic systems are likely to have a fundamental role in the development of graft-induced dyskinesias, which are mechanistically distinct from L-DOPA-induced behvaviours. Importantly, the expression of D₁ and D₂ receptors was unrelated to the severity of AIMs.

  6. Effect of Sarizotan, a 5-HT1a and D2-Like Receptor Agonist, on Respiration in Three Mouse Models of Rett Syndrome

    PubMed Central

    Abdala, Ana P.; Lioy, Daniel T.; Garg, Saurabh K.; Knopp, Sharon J.; Paton, Julian F. R.

    2014-01-01

    Disturbances in respiration are common and debilitating features of Rett syndrome (RTT). A previous study showed that the 5-HT1a receptor agonist (R)-(+)-8-hydroxy-dipropyl-2-aminotetralin hydrobromide (8-OH-DPAT) significantly reduced the incidence of apnea and the irregular breathing pattern in a mouse model of the disorder. 8-OH-DPAT, however, is not available for clinical practice. Sarizotan, a full 5-HT1a agonist and a dopamine D2–like agonist/partial agonist, has been used in clinical trials for the treatment of l-dopa–induced dyskinesia. The purpose of this study was to evaluate the effects of sarizotan on respiration and locomotion in mouse models of RTT. Studies were performed in Bird and Jaenisch strains of methyl-CpG–binding protein 2-–deficient heterozygous female and Jaenisch strain Mecp2 null male mice and in knock-in heterozygous female mice of a common nonsense mutation (R168X). Respiratory pattern was determined with body plethysmography, and locomotion was determined with open-field recording. Sarizotan or vehicle was administered 20 minutes before a 30-minute recording of respiratory pattern or motor behavior. In separate studies, a crossover design was used to administer the drug for 7 and for 14 days. Sarizotan reduced the incidence of apnea in all three RTT mouse models to approximately 15% of their pretreatment levels. The irregular breathing pattern was corrected to that of wild-type littermates. When administered for 7 or 14 days, apnea decreased to 25 to 33% of the incidence seen with vehicle. This study indicates that the clinically approved drug sarizotan is an effective treatment for respiratory disorders in mouse models of RTT. PMID:24351104

  7. 5-Hydroxytryptamine 1A receptors in the dorsomedial hypothalamus connected to dorsal raphe nucleus inputs modulate defensive behaviours and mediate innate fear-induced antinociception.

    PubMed

    Biagioni, Audrey Franceschi; de Oliveira, Rithiele Cristina; de Oliveira, Ricardo; da Silva, Juliana Almeida; dos Anjos-Garcia, Tayllon; Roncon, Camila Marroni; Corrado, Alexandre Pinto; Zangrossi, Hélio; Coimbra, Norberto Cysne

    2016-03-01

    The dorsal raphe nucleus (DRN) is an important brainstem source of 5-hydroxytryptamine (5-HT), and 5-HT plays a key role in the regulation of panic attacks. The aim of the present study was to determine whether 5-HT1A receptor-containing neurons in the medial hypothalamus (MH) receive neural projections from DRN and to then determine the role of this neural substrate in defensive responses. The neurotracer biotinylated dextran amine (BDA) was iontophoretically microinjected into the DRN, and immunohistochemical approaches were then used to identify 5HT1A receptor-labelled neurons in the MH. Moreover, the effects of pre-treatment of the dorsomedial hypothalamus (DMH) with 8-OH-DPAT and WAY-100635, a 5-HT1A receptor agonist and antagonist, respectively, followed by local microinjections of bicuculline, a GABAA receptor antagonist, were investigated. We found that there are many projections from the DRN to the perifornical lateral hypothalamus (PeFLH) but also to DMH and ventromedial (VMH) nuclei, reaching 5HT1A receptor-labelled perikarya. DMH GABAA receptor blockade elicited defensive responses that were followed by antinociception. DMH treatment with 8-OH-DPAT decreased escape responses, which strongly suggests that the 5-HT1A receptor modulates the defensive responses. However, DMH treatment with WAY-100635 failed to alter bicuculline-induced defensive responses, suggesting that 5-HT exerts a phasic influence on 5-HT1A DMH neurons. The activation of the inhibitory 5-HT1A receptor had no effect on antinociception. However, blockade of the 5-HT1A receptor decreased fear-induced antinociception. The present data suggest that the ascending pathways from the DRN to the DMH modulate panic-like defensive behaviours and mediate antinociceptive phenomenon by recruiting 5-HT1A receptor in the MH.

  8. Chronic Sarpogrelate Treatment Reveals 5-HT7 Receptor in the Serotonergic Inhibition of the Rat Vagal Bradycardia.

    PubMed

    García-Pedraza, José Ángel; García, Mónica; Martín, María Luisa; Eleno, Nélida; Morán, Asunción

    2017-01-01

    5-Hydroxytryptamine (5-HT) modulates the cardiac parasympathetic neurotransmission, inhibiting the bradyarrhythmia by 5-HT2 receptor activation. We aimed to determine whether the chronic selective 5-HT2 blockade (sarpogrelate) could modify the serotonergic modulation on vagal cardiac outflow in pithed rat. Bradycardic responses in rats treated with sarpogrelate (30 mg·kg·d; orally) were obtained by electrical stimulation of the vagal fibers (3, 6, and 9 Hz) or intravenous (IV) injections of acetylcholine (1, 5, and 10 μg/kg). 5-HT7 receptor expression was quantified by Western blot in vagus nerve and right atrium. The IV administration of 5-HT (10-200 μg/kg) dose dependently decreased the vagally induced bradycardia, and agonists 5-CT (5-HT1/7), 8-OH-DPAT (5-HT1A), or AS-19 (5-HT7) (50 μg/kg each) mimicked the 5-HT-induced inhibitory effect. Neither agonists CGS-12066B (5-HT1B), L-694,247 (5-HT1D), nor 1-phenylbiguanide (5-HT3) modified the electrically-induced bradycardic responses. Moreover, SB-258719 (5-HT7 antagonist) abolished the 5-HT-, 5-CT-, 8-OH-DPAT-, and AS-19-induced bradycardia inhibition; 5-HT or AS-19 did not modify the bradycardia induced by IV acetylcholine; and 5-HT7 receptor was expressed in both the vagus nerve and the right atrium. Our outcomes suggest that blocking chronically 5-HT2 receptors modifies the serotonergic influence on cardiac vagal neurotransmission exhibiting 5-HT as an exclusively inhibitory agent via prejunctional 5-HT7 receptor.

  9. Roles of the serotonin 5-HT4 receptor in dendrite formation of the rat hippocampal neurons in vitro.

    PubMed

    Kozono, Naoki; Ohtani, Akiko; Shiga, Takashi

    2017-01-15

    Serotonin (5-HT) is involved in various aspects of hippocampal development, although the specific roles of 5-HT receptors are poorly understood. We investigated the roles of 5-HT receptors in the dendrite formation of hippocampal neurons. We focused on the 5-HT4 receptor, which is coupled with Gs protein, and compared the effects with those of the Gi-coupled 5-HT1A receptor. Neurons from rat hippocampi at embryonic day 18 were dissociated and treated for 4 days with the 5-HT4 receptor agonist BIMU8 or the 5-HT1A receptor agonist 8-OH DPAT. The formation of primary dendrites and dendrite branching were promoted by BIMU8, whereas the dendrite branching was inhibited by 8-OH DPAT. BIMU8-induced promotion of dendrite formation was neutralized by concomitant treatment with the 5-HT4 receptor antagonist, confirming the specific actions of the 5-HT4 receptor. We then examined the signaling mechanisms underlying the actions of the 5-HT4 receptor by using a protein kinase A (PKA) inhibitor. The BIMU8-induced promotion of dendrite formation was reversed partially by the PKA inhibitor, suggesting involvement of PKA signaling downstream of the 5-HT4 receptor. Finally, we examined the contribution of brain-derived neurotrophic factor (BDNF) to the promotion of dendrite formation by BIMU8. Quantitative RT-PCR analysis showed that BIMU8 increased the BDNF mRNA expression and that treatment of cultured neurons with the TrkB antagonist reversed the BIMU8-induced increase in dendrite formation. In summary, the present study suggests a novel role for the 5-HT4 receptor in facilitation of dendrite formation in which intracellular signaling of PKA and the BDNF-TrkB system may be involved.

  10. Depressed GABA and glutamate synaptic signaling by 5-HT1A receptors in the nucleus tractus solitarii and their role in cardiorespiratory function

    PubMed Central

    Ostrowski, Tim D.; Ostrowski, Daniela; Hasser, Eileen M.

    2014-01-01

    Serotonin (5-HT), and its 5-HT1A receptor (5-HT1AR) subtype, is a powerful modulator of the cardiorespiratory system and its sensory reflexes. The nucleus tractus solitarii (nTS) serves as the first central station for visceral afferent integration and is critical for cardiorespiratory reflex responses. However, the physiological and synaptic role of 5-HT1ARs in the nTS is relatively unknown. In the present study, we examined the distribution and modulation of 5-HT1ARs on cardiorespiratory and synaptic parameters in the nTS. 5-HT1ARs were widely distributed to cell bodies within the nTS but not synaptic terminals. In anesthetized rats, activation of 5-HT1ARs by microinjection of the 5-HT1AR agonist 8-OH-DPAT into the caudal nTS decreased minute phrenic neural activity via a reduction in phrenic amplitude. In brain stem slices, 8-OH-DPAT decreased the amplitude of glutamatergic tractus solitarii-evoked excitatory postsynaptic currents, and reduced overall spontaneous excitatory nTS network activity. These effects persisted in the presence of GABAA receptor blockade and were antagonized by coapplication of 5-HT1AR blocker WAY-100135. 5-HT1AR blockade alone had no effect on tractus solitarii-evoked excitatory postsynaptic currents, but increased excitatory network activity. On the other hand, GABAergic nTS-evoked inhibitory postsynaptic currents did not change by activation of the 5-HT1ARs, but spontaneous inhibitory nTS network activity decreased. Blocking 5-HT1ARs tended to increase nTS-evoked inhibitory postsynaptic currents and inhibitory network activity. Taken together, 5-HT1ARs in the caudal nTS decrease breathing, likely via attenuation of afferent transmission, as well as overall nTS network activity. PMID:24671532

  11. Effect of Sarizotan, a 5-HT1a and D2-like receptor agonist, on respiration in three mouse models of Rett syndrome.

    PubMed

    Abdala, Ana P; Lioy, Daniel T; Garg, Saurabh K; Knopp, Sharon J; Paton, Julian F R; Bissonnette, John M

    2014-06-01

    Disturbances in respiration are common and debilitating features of Rett syndrome (RTT). A previous study showed that the 5-HT1a receptor agonist (R)-(+)-8-hydroxy-dipropyl-2-aminotetralin hydrobromide (8-OH-DPAT) significantly reduced the incidence of apnea and the irregular breathing pattern in a mouse model of the disorder. 8-OH-DPAT, however, is not available for clinical practice. Sarizotan, a full 5-HT1a agonist and a dopamine D2-like agonist/partial agonist, has been used in clinical trials for the treatment of l-dopa-induced dyskinesia. The purpose of this study was to evaluate the effects of sarizotan on respiration and locomotion in mouse models of RTT. Studies were performed in Bird and Jaenisch strains of methyl-CpG-binding protein 2--deficient heterozygous female and Jaenisch strain Mecp2 null male mice and in knock-in heterozygous female mice of a common nonsense mutation (R168X). Respiratory pattern was determined with body plethysmography, and locomotion was determined with open-field recording. Sarizotan or vehicle was administered 20 minutes before a 30-minute recording of respiratory pattern or motor behavior. In separate studies, a crossover design was used to administer the drug for 7 and for 14 days. Sarizotan reduced the incidence of apnea in all three RTT mouse models to approximately 15% of their pretreatment levels. The irregular breathing pattern was corrected to that of wild-type littermates. When administered for 7 or 14 days, apnea decreased to 25 to 33% of the incidence seen with vehicle. This study indicates that the clinically approved drug sarizotan is an effective treatment for respiratory disorders in mouse models of RTT.

  12. Relationship between Rgs2 gene expression level and anxiety and depression-like behaviour in a mutant mouse model: serotonergic involvement.

    PubMed

    Lifschytz, Tzuri; Broner, Esther Channah; Zozulinsky, Polina; Slonimsky, Alexandra; Eitan, Renana; Greenbaum, Lior; Lerer, Bernard

    2012-10-01

    RGS2 is a member of a family of proteins that negatively modulate G-protein coupled receptor transmission. Variations in the RGS2 gene were found to be associated in humans with anxious and depressive phenotypes. We sought to study the relationship of Rgs2 expression level to depression and anxiety-like behavioural features, sociability and brain 5-HT1A and 5-HT1B receptor expression. We studied male mice carrying a mutation that causes lower Rgs2 gene expression, employing mice heterozygous (Het) or homozygous (Hom) for this mutation, or wild-type (WT). Mice were subjected to behavioural tests reflecting depressive-like behaviour [forced swim test (FST), novelty suppressed feeding test (NSFT)], elevated plus maze (EPM) for evaluation of anxiety levels and the three-chamber sociability test. The possible involvement of raphe nucleus 5-HT1A receptors in these behavioural features was examined by 8-OH-DPAT-induced hypothermia. Expression levels of 5-HT1A and 5-HT1B receptors in the cortex, raphe nucleus and hypothalamus were compared among mice of the different Rgs2 genotype groups. NSFT results demonstrated that Hom mice showed more depressive-like features than Rgs2 Het and WT mice. A trend for such a relationship was also suggested by the FST results. EPM and sociability test results showed Hom and Het mice to be more anxious and less sociable than WT mice. In addition Hom and Het mice were characterized by lower basal body temperature and demonstrated less 8-OH-DPAT-induced hypothermia than WT mice. Finally, Hom and Het mice had significantly lower 5-HT1A and 5-HT1B receptor expression levels in the raphe than WT mice. Our findings demonstrate a relationship between Rgs2 gene expression level and a propensity for anxious and depressive-like behaviour and reduced social interaction that may involve changes in serotonergic receptor expression.

  13. 5-HT(1A) and NMDA receptors interact in the rat medial septum and modulate hippocampal-dependent spatial learning.

    PubMed

    Elvander-Tottie, Elin; Eriksson, Therese M; Sandin, Johan; Ogren, Sven Ove

    2009-12-01

    Cholinergic and GABAergic neurons in the medial septum/vertical limb of the diagonal band of Broca (MS/vDB) projecting to the hippocampus, constitute the septohippocampal projection, which is important for hippocampal-dependent learning and memory. There is also evidence for an extrinsic as well as an intrinsic glutamatergic network within the MS/vDB. GABAergic and cholinergic septohippocampal neurons express the serotonergic 5-HT(1A) receptor and most likely also glutamatergic NMDA receptors. The aim of the present study was to examine whether septal 5-HT(1A) receptors are important for hippocampal-dependent long-term memory and whether these receptors interact with glutamatergic NMDA receptor transmission in a manner important for hippocampal-dependent spatial memory. Intraseptal infusion of the 5-HT(1A) receptor agonist (R)-8-OH-DPAT (1 or 4 microg/rat) did not affect spatial learning in the water maze task but impaired emotional memory in the passive avoidance task at the higher dose tested (4 microg/rat). While intraseptal administration of (R)-8-OH-DPAT (4 microg) combined with a subthreshold dose of the NMDA receptor antagonist D-AP5 (1 microg) only marginally affected spatial acquisition, it produced a profound impairment in spatial memory. In conclusion, septal 5-HT(1A) receptors appears to play a more prominent role in emotional than in spatial memory. Importantly, septal 5-HT(1A) and NMDA receptors appear to interact in a manner, which is particularly critical for the expression or retrieval of hippocampal-dependent long-term spatial memory. It is proposed that NMDA receptor hypofunction in the septal area may unmask a negative effect of 5-HT(1A) receptor activation on memory, which may be clinically relevant.

  14. Heterologous Expression in Remodeled C. elegans: A Platform for Monoaminergic Agonist Identification and Anthelmintic Screening

    PubMed Central

    Law, Wenjing; Wuescher, Leah M.; Ortega, Amanda; Hapiak, Vera M.; Komuniecki, Patricia R.; Komuniecki, Richard

    2015-01-01

    Monoamines, such as 5-HT and tyramine (TA), paralyze both free-living and parasitic nematodes when applied exogenously and serotonergic agonists have been used to clear Haemonchus contortus infections in vivo. Since nematode cell lines are not available and animal screening options are limited, we have developed a screening platform to identify monoamine receptor agonists. Key receptors were expressed heterologously in chimeric, genetically-engineered Caenorhabditis elegans, at sites likely to yield robust phenotypes upon agonist stimulation. This approach potentially preserves the unique pharmacologies of the receptors, while including nematode-specific accessory proteins and the nematode cuticle. Importantly, the sensitivity of monoamine-dependent paralysis could be increased dramatically by hypotonic incubation or the use of bus mutants with increased cuticular permeabilities. We have demonstrated that the monoamine-dependent inhibition of key interneurons, cholinergic motor neurons or body wall muscle inhibited locomotion and caused paralysis. Specifically, 5-HT paralyzed C. elegans 5-HT receptor null animals expressing either nematode, insect or human orthologues of a key Gαo-coupled 5-HT1-like receptor in the cholinergic motor neurons. Importantly, 8-OH-DPAT and PAPP, 5-HT receptor agonists, differentially paralyzed the transgenic animals, with 8-OH-DPAT paralyzing mutant animals expressing the human receptor at concentrations well below those affecting its C. elegans or insect orthologues. Similarly, 5-HT and TA paralyzed C. elegans 5-HT or TA receptor null animals, respectively, expressing either C. elegans or H. contortus 5-HT or TA-gated Cl- channels in either C. elegans cholinergic motor neurons or body wall muscles. Together, these data suggest that this heterologous, ectopic expression screening approach will be useful for the identification of agonists for key monoamine receptors from parasites and could have broad application for the identification

  15. Behavioral characterization of serotonergic activation in the flatworm Planaria.

    PubMed

    Farrell, Martilias S; Gilmore, Kirsti; Raffa, Robert B; Walker, Ellen A

    2008-05-01

    Serotonin (5-hydroxytryptamine, 5-HT) receptors have been identified in Planaria, a model used for studying the pharmacology of behavioral phenomena. This study characterized the behavioral and locomotor effects of 5-HT, a 5-HT1A agonist, a 5-HT1B/2C agonist, and a 5-HT1A antagonist to examine the role of 5-HT receptor activation in this species. Planarians were video recorded individually in a clear plastic cube containing drug solution or vehicle. To quantify locomotor velocity (pLMV), planarians were placed individually into a dish containing drug solution or vehicle and the rate of gridline crossings was recorded. For the antagonist experiments, four conditions were studied: water alone, agonist alone, antagonist alone, and agonist plus antagonist. The decrease in pLMV induced by the5-HT1A agonist (8-OH-DPAT), and the 5-HT1B/2C agonist (mCPP), was antagonized by pretreatment with the 5-HT1A antagonist (WAY-100635) at a dose that had no effect of its own on pLMV. At a higher concentration of WAY-100635, further decreases in pLMV induced by 8-OH-DPAT were observed. Each agonist produced increased occurrences of 'C-like position' and 'screw-like hyperkinesia', 5-HT and mCPP produced 'writhing', and only mCPP produced a significant increase in duration of 'headswing' behavior. The results demonstrate that the 5-HT1A receptor identified in Planaria mediates behavioral responses to 5-HT receptor ligands, supporting the notion that planarians possess functional 5-HT receptors and might serve as a simple model for their study.

  16. Antidepressant-like activity of Tagetes lucida Cav. is mediated by 5-HT(1A) and 5-HT(2A) receptors.

    PubMed

    Bonilla-Jaime, H; Guadarrama-Cruz, G; Alarcon-Aguilar, F J; Limón-Morales, O; Vazquez-Palacios, G

    2015-10-01

    It has been demonstrated that the aqueous extract of Tagetes lucida Cav. shows an antidepressant-like effect on the forced swimming test (FST) in rats. The aim of this study was to analyze the participation of the serotoninergic system in the antidepressant-like effect of the aqueous extract of T. lucida. Different doses of the extract of T. lucida were administered at 72, 48, 24, 18 and 1 h before FST. The animals were pretreated with a 5-HT1A receptor antagonist (WAY-100635, 0.5 mg/kg), a 5-HT2A receptor antagonist (ketanserin, 5 mg/kg), a β-noradrenergic receptor antagonist (propranolol, 200 mg/kg), and with a α2-noradrenergic receptor antagonist (yohimbine, 1 mg/kg) alone or combined with the extract and pretreated with a serotonin synthesis inhibitor (PCPA) before treatment with 8-OH-DPAT + the extract of T. lucida. In addition, suboptimal doses of the 5-HT1A agonist (8-OH-DPAT) + non-effective dose of extract was analyzed in the FST. To determine the presence of flavonoids, the aqueous extract of T. lucida (20 µl, 4 mg/ml) was injected in HPLC; however, a quercetin concentration of 7.72 mg/g of extract weight was detected. A suboptimal dose of 8-OH-DPAT + extract of T. lucida decreased immobility and increased swimming and climbing. An antidepressant-like effect with the aqueous extract of T. lucida at doses of 100 and 200 mg/kg was observed on the FST with decreased immobility behavior and increased swimming; however, this effect was blocked by WAY-100635, ketanserin and PCPA but not by yohimbine and propranolol, suggesting that the extract of T. lucida could be modulating the release/reuptake of serotonin.

  17. Selective 5-HT7 Receptor Activation May Enhance Synaptic Plasticity Through N-methyl-D-aspartate (NMDA) Receptor Activity in the Visual Cortex.

    PubMed

    Xiang, Kangjian; Zhao, Xuefei; Li, Youjun; Zheng, Liang; Wang, Jue; Li, Yan-Hai

    2016-01-01

    Serotonin (5-hydroxytryptamine, 5-HT) is an important neurotransmitter that modulates N-methyl-D-aspartate (NMDA) receptor activity by binding to several different 5-HT receptor subtypes. In the present study, we used whole-cell patch-clamp recordings in transverse slice preparations to test the role of 5-HT receptors in modulating the NMDA receptor-mediated miniature excitatory postsynaptic currents (mEPSCs) in layer II/III pyramidal neurons of the rat visual cortex. We found that the NMDA receptor-mediated component of mEPSCs could be potentiated by exogenously applied 5-HT. Similar results were obtained by exogenously applied 5-CT or 8-OH-DPAT (the 5-HT1A and 5-HT7 receptor agonist). A specific antagonist for the 5-HT7 receptor, SB-269970, completely blocked the increase in NMDA receptor-mediated component of mEPSCs by 5-CT or 8- OH-DPAT. Moreover, the selective 5-HT1A receptor antagonist, WAY-100135, displayed no influence on the enhancement in NMDA receptor-mediated component of mEPSCs by 5-CT or 8-OHDPAT. These results indicated that the increase in NMDA receptor-mediated component of mEPSCs by 5-HT in layer II/III pyramidal neurons of the young rat visual cortex requires activation of 5-HT7 receptors, but not 5-HT1A receptors. These observations might be clinically relevant to schizophrenia and Alzheimer's disease (AD), where enhancing NMDA receptor-mediated neurotransmission is considered to be a promising strategy for treatment of these diseases.

  18. Repeated co-treatment with imipramine and amantadine induces hippocampal brain-derived neurotrophic factor gene expression in rats.

    PubMed

    Rogóz, Z; Skuza, G; Legutko, B

    2007-06-01

    The problem of drug-resistant depression indicates a strong need for alternative antidepressant therapies. In our earlier papers we described synergistic, antidepressant-like effects of a combination of imipramine (IMI) and amantadine (AMA) in the forced swimming test in rats, an animal model of depression. Moreover, preliminary clinical data showed that the above-mentioned combination had beneficial effects in treatment-resistant patients. In addition, a number of studies predicted a role of the brain-derived neurotrophic factor (BDNF) in the mechanism of action of antidepressant drugs (ADs). Since the most potent effect of ADs on BDNF gene expression was found after prolonged treatment, in the present study we investigated the influence of repeated treatment with IMI (5 or 10 mg/kg) and AMA (10 mg/kg), given separately or jointly (twice daily for 14 day), on mRNA level (the Northern blot) in the hippocampus and cerebral cortex. The experiment was carried out on male Wistar rats. The tissue for biochemical assays was dissected 24 h after the last dose of IMI and AMA. We also studied the effect of repeated treatment with IMI and AMA on the action of 5-HT(1A)- and 5-HT(2A) receptor agonists (8-OH-DPAT and (+/-)DOI, respectively) in behavioral tests. The obtained results showed that in the hippocampus IMI (10 mg/kg), and in the cerebral cortex IMI (5 and 10 mg/kg) and AMA (10 mg/kg) significantly elevated BDNF mRNA level. Joint administration of IMI (5 or 10 mg/kg) and AMA (10 mg/kg) induced a more potent increase BDNF gene expression in the hippocampus (but not in cerebral cortex) and either inhibited the behavioral syndrome induced by (+/-)DOI or did not change the action of 8-OH-DPAT (compared to treatment with either drug alone). The obtained results suggest that the enhancement of BDNF gene expression may be essential for the therapeutic effect of co-administration of IMI and AMA to drug-resistant depressed patients, and that among other mechanisms, 5-HT(2A

  19. Nicotine alters limbic function in adolescent rat by a 5-HT1A receptor mechanism.

    PubMed

    Dao, Jasmin M; McQuown, Susan C; Loughlin, Sandra E; Belluzzi, James D; Leslie, Frances M

    2011-06-01

    Epidemiological studies have shown that adolescent smoking is associated with health risk behaviors, including high-risk sexual activity and illicit drug use. Using rat as an animal model, we evaluated the behavioral and biochemical effects of a 4-day, low-dose nicotine pretreatment (60 μg/kg; intravenous) during adolescence and adulthood. Nicotine pretreatment significantly increased initial acquisition of cocaine self-administration, quinpirole-induced locomotor activity, and penile erection in adolescent rats, aged postnatal day (P)32. These effects were long lasting, remaining evident 10 days after the last nicotine treatment, and were observed when nicotine pretreatment was administered during early adolescence (P28-31), but not late adolescence (P38-41) or adulthood (P86-89). Neurochemical analyses of c-fos mRNA expression, and of monoamine transmitter and transporter levels, showed that forebrain limbic systems are continuing to develop during early adolescence, and that this maturation is critically altered by brief nicotine exposure. Nicotine selectively increased c-fos mRNA expression in the nucleus accumbens shell and basolateral amygdala in adolescent, but not adult animals, and altered serotonin markers in these regions as well as the prefrontal cortex. Nicotine enhancement of cocaine self-administration and quinpirole-induced locomotor activity was blocked by co-administration of WAY 100 635 (N-{2-[4-(2-methoxyphenyl)-1-piperazinyl] ethyl}-N-(2-pyridinyl)cyclohexanecarboxamide), a selective serotonin 1A (5-HT1A) receptor antagonist. Early adolescent pretreatment with the mixed autoreceptor/heteroceptor 5-HT1A receptor agonist, 8-OH-DPAT, but not the autoreceptor-selective agonist, S-15535, also enhanced quinpirole-induced locomotor activation. Nicotine enhancement of quinpirole-induced penile erection was not blocked by WAY 100 635 nor mimicked by 8-OH-DPAT. These findings indicate that early adolescent nicotine exposure uniquely alters limbic

  20. Estradiol accelerates the effects of fluoxetine on serotonin 1A receptor signaling.

    PubMed

    Li, Qian; Sullivan, Nicole R; McAllister, Carrie E; Van de Kar, Louis D; Muma, Nancy A

    2013-07-01

    A major problem with current anti-depressant therapy is that it takes on average 6-7 weeks for remission. Since desensitization of serotonin (5-HT)1A receptor signaling contributes to the anti-depressive response, acceleration of the desensitization may reduce this delay in response to antidepressants. The purpose of the present study was to test the hypothesis that estradiol accelerates fluoxetine-induced desensitization of 5-HT1A receptor signaling in the paraventricular nucleus of the hypothalamus (PVN) of rats, via alterations in components of the 5-HT1A receptor signaling pathway. Ovariectomized rats were injected with estradiol and/or fluoxetine, then adrenocorticotropic hormone (ACTH) and oxytocin responses to a 5-HT1A receptor agonist (+)-8-hydroxy-2-dipropylaminotetralin (8-OH-DPAT) were examined to assess the function of 5-HT1A receptors in the PVN. Treatment with estradiol for either 2 or 7 days or fluoxetine for 2 days produced at most a partial desensitization of 5-HT1A receptor signaling, whereas 7 days of fluoxetine produced full desensitization. Combined treatment with estradiol and fluoxetine for 2 days produced nearly a full desensitization, demonstrating an accelerated response compared to either treatment alone. With two days of combined treatments, estradiol prevented the fluoxetine-induced increase in 5-HT1A receptor protein, which could contribute to the more rapid desensitization. Furthermore, EB treatment for 2 days decreased the abundance of the 35 kD Gαz protein which could contribute to the desensitization response. We found two isoforms of Gαz proteins with molecular mass of 35 and 33 kD, which differentially distributed in the detergent resistant microdomain (DRM) and in Triton X-100 soluble membrane region, respectively. The 35 kD Gαz proteins in the DRM can be sumoylated by SUMO1. Stimulation of 5-HT1A receptors with 8-OH-DPAT increases the sumoylation of Gαz proteins and reduces the 33 kD Gαz proteins, suggesting that these

  1. Signal transduction and functional selectivity of F15599, a preferential post-synaptic 5-HT1A receptor agonist

    PubMed Central

    Newman-Tancredi, A; Martel, J-C; Assié, M-B; Buritova, J; Lauressergues, E; Cosi, C; Heusler, P; Slot, L Bruins; Colpaert, FC; Vacher, B; Cussac, D

    2009-01-01

    Background and purpose: Activation of post-synaptic 5-HT1A receptors may provide enhanced therapy against depression. We describe the signal transduction profile of F15599, a novel 5-HT1A receptor agonist. Experimental approach: F15599 was compared with a chemical congener, F13714, and with (+)8-OH-DPAT in models of signal transduction in vitro and ex vivo. Key results: F15599 was highly selective for 5-HT1A receptors in binding experiments and in [35S]-GTPγS autoradiography of rat brain, where F15599 increased labelling in regions expressing 5-HT1A receptors. In cell lines expressing h5-HT1A receptors, F15599 more potently stimulated extracellular signal-regulated kinase (ERK1/2) phosphorylation, compared with G-protein activation, internalization of h5-HT1A receptors or inhibition of cAMP accumulation. F13714, (+)8-OH-DPAT and 5-HT displayed a different rank order of potency for these responses. F15599 stimulated [35S]-GTPγS binding more potently in frontal cortex than raphe. F15599, unlike 5-HT, more potently and efficaciously stimulated Gαi than Gαo activation. In rat prefrontal cortex (a region expressing post-synaptic 5-HT1A receptors), F15599 potently activated ERK1/2 phosphorylation and strongly induced c-fos mRNA expression. In contrast, in raphe regions (expressing pre-synaptic 5-HT1A receptors) F15599 only weakly or did not induce c-fos mRNA expression. Finally, despite its more modest affinity in vitro, F15599 bound to 5-HT1A receptors in vivo almost as potently as F13714. Conclusions and implications: F15599 showed a distinctive activation profiles for 5-HT1A receptor-mediated signalling pathways, unlike those of reference agonists and consistent with functional selectivity at 5-HT1A receptors. In rat, F15599 potently activated signalling in prefrontal cortex, a feature likely to underlie its beneficial effects in models of depression and cognition. PMID:19154445

  2. The theta-related firing activity of parvalbumin-positive neurons in the medial septum-diagonal band of Broca complex and their response to 5-HT1A receptor stimulation in a rat model of Parkinson's disease.

    PubMed

    Li, Li-Bo; Han, Ling-Na; Zhang, Qiao-Jun; Sun, Yi-Na; Wang, Yong; Feng, Jie; Zhang, Li; Wang, Tao; Chen, Li; Liu, Jian

    2014-03-01

    The parvalbumin (PV)-positive neurons in the medial septum-diagonal band of Broca complex (MS-DB) play an important role in the generation of hippocampal theta rhythm involved in cognitive functions. These neurons in this region express a high density of 5-HT1A receptors which regulate the neuronal activity and consequently affect the theta rhythm. In this study, we examined changes in the theta-related firing activity of PV-positive neurons in the MS-DB, their response to 5-HT1A receptor stimulation and the corresponding hippocampal theta rhythm, and the density of PV-positive neurons and their co-localization with 5-HT1A receptors in rats with 6-hydroxydopamine lesions of the substantia nigra pars compacta (SNc). The lesion of the SNc decreased the rhythmically bursting activity of PV-positive neurons and the peak frequency of hippocampal theta rhythm. Systemic administration of 5-HT1A receptor agonist 8-OH-DPAT (0.5-128 µg/kg, i.v.) inhibited the firing rate of PV-positive neurons and disrupted rhythmically bursting activity of the neurons and the theta rhythm in sham-operated and the lesioned rats, respectively. The cumulative doses producing inhibition and disruption in the lesioned rats were higher than that of sham-operated rats. Furthermore, local application of 8-OH-DPAT (0.005 μg) in the MS-DB also inhibited the firing rate of PV-positive neurons and disrupted their rhythmically bursting activity in sham-operated rats, while having no effect on PV-positive neurons in the lesioned rats. The lesion of the SNc decreased the density of PV-positive neurons in the MS-DB, and percentage of PV-positive neurons expressing 5-HT1A receptors. These results indicate that the lesion of the SNc leads to suppression of PV-positive neurons in the MS-DB and hippocampal theta rhythm. Furthermore, the lesion decreases the response of these neurons to 5-HT1A receptor stimulation, which attributes to dysfunction and/or down-regulation of 5-HT1A receptor expression on these

  3. Short-term effect on intestinal epithelial Na(+)/H(+) exchanger by Gi(alpha1,2)-coupled 5-HT(1A) and G(q/11)-coupled 5-HT(2) receptors.

    PubMed

    Magro, Fernando; Fraga, Sónia; Soares-da-Silva, Patrício

    2007-07-26

    The present study evaluated the effect of 5-hydroxytryptamine (5-HT) on intestinal Na(+)/H(+) exchanger (NHE) activity and the cellular signaling pathways involved in T84 cells. T84 cells express endogenous NHE1 and NHE2 proteins, detected by immunoblotting, but not NHE3. The rank order for inhibition of NHE activity in acid-loaded T84 cells was 5-(N-ethyl-N-isopropyl)-amiloride (EIPA; IC(50)=519 [465, 579] nM)>cariporide (IC(50)=630 [484, 819] nM)>amiloride (IC(50)=19 [16, 24] microM); the NHE3 inhibitor S3226 was found to be devoid of effect. This different inhibitory sensitivity indicates that both NHE1 and NHE2 isoforms may play an active role in Na(+)-dependent intracellular pH (pH(i)) recovery in T84 cells. Short-term exposure (0.5 h) of T84 cells to 5-HT increased NHE activity in a concentration-dependent manner. The stimulation induced by 5-HT (30 microM) was partially inhibited by both WAY 100135 (300 nM) and ketanserin (300 nM), antagonists of 5-HT(1A) and 5-HT(2) receptors, respectively. NHE activity was significantly increased by 8-OH-DPAT and alpha-methyl-5-HT, agonists of, respectively, 5-HT(1A) and 5-HT(2) receptors. An incubation of T84 cells with anti-G(s) and anti-G(beta) antibodies complexed with lipofectin did not prevent the 5-HT-induced stimulation of NHE activity. Overnight treatment with anti-G(ialpha1,2) and anti-G(q/11) antibodies complexed with lipofectin blocked the stimulatory effect induced by 8-OH-DPAT and alpha-methyl-5-HT, respectively. It is concluded that in T84 cells 5-HT enhances intestinal NHE activity through stimulation of G(ialpha1,2)-coupled 5-HT(1A) and G(q/11)-coupled 5-HT(2) receptors.

  4. 5-HT(1A)-receptor over-expressing mice: genotype and sex dependent responses to antidepressants in the forced swim-test.

    PubMed

    Günther, Lydia; Rothe, Julia; Rex, André; Voigt, Jörg-Peter; Millan, Mark J; Fink, Heidrun; Bert, Bettina

    2011-09-01

    Deficiencies in serotonergic neurotransmission are involved in the pathophysiology of depression. Due to its modulatory effect on serotonin (5-HT) release, the 5-HT(1A)-receptor is thought to play a decisive role in the therapy of this mood disorder. However, it is not fully understood how antidepressant effects are mediated by pre- and postsynaptic receptor sites. In this study we examined the impact of postsynaptic 5-HT(1A)-receptor over-expression in corticolimbic areas of male and female mice on the performance in the forced swim-test (FST). Furthermore, we investigated their response to the serotonin selective reuptake inhibitor (SSRI) citalopram in comparison to the selective noradrenaline reuptake inhibitor reboxetine, as well as the partial 5-HT(1A)-receptor agonists, buspirone and S 15535. Additionally, these drugs were evaluated in the open field-test in order to observe effects on motor activity. The density of 5-HT(1A)-receptors in discrete corticolimbic regions was determined in detail by quantitative autoradiography with [(3)H]8-OH-DPAT to investigate genotype as well as sex dependent differences in the expression pattern. [(3)H]8-OH-DPAT binding differed depending on sex with female mice of both genotypes displaying higher receptor binding in distinct brain areas. In the FST untreated male but not female over-expressing (OE) mice showed an antidepressant-like behaviour compared to wild-type (WT) mice. Citalopram yielded an antidepressant effect without influencing locomotor activity in OE mice but not in WT mice. Reboxetine had no antidepressant-like effect in OE mice, but sex-dependently in WT mice. The two partial agonists, buspirone and S 15535 produced no antidepressant-like activity in both genotypes and sexes, but aberrant motor effects. The antidepressant-like phenotype of male transgenic mice accounts for an involvement of postsynaptic 5-HT(1A)-receptors in the FST behaviour. In addition, the selective over-expression of postsynaptic 5-HT(1A

  5. Shock priming enhances the efficacy of SSRIs in the foot shock-induced ultrasonic vocalization test.

    PubMed

    Kassai, Ferenc; Gyertyán, István

    2012-01-10

    Data on the effect of acutely administered serotonin reuptake inhibitors (SSRIs) in animal anxiety models have been inconsistent. In some of the models these compounds showed anxiolytic properties, while in others they were ineffective or even anxiogenic. In the foot shock-induced ultrasonic vocalization (USV) test in the adult rat, SSRIs were reported to be effective, however, they were only tested with protocols using multiple shocking design. In the present study, anxiolytic effects of various SSRI compounds (sertraline, fluoxetine, paroxetine, escitalopram) were tested in three distinct USV test protocols in comparison with alprazolam and 8-OH-DPAT. In the single shocking protocol, animals were exposed to one shocking session after the drug treatment. In the multiple shocking protocol, rats went through a foot shock priming session before each drug test. On priming days animals received foot shocks without drug treatment. On the test day (the day after), rats received drug treatment and then were shocked again. In the context conditioning protocol animals were exposed to foot shocks on two consecutive days before the drug test. On the third, test day, after drug treatment animals were replaced to the shocking chamber, but this time shocks were not delivered. SSRIs were ineffective using the single shocking protocol. In the context conditioned protocol, all SSRIs showed linear dose-response relationship with ED50 values of 8.5, 2.2, 0.77 and 0.93 mg/kg i.p. for fluoxetine, sertraline, paroxetine and escitalopram, respectively. Using the multiple shocking protocol, SSRIs were only partially effective with maximum inhibitions ranging between 44% and 62%. In contrast to SSRIs, the benzodiazepine anxiolytics, alprazolam showed anxiolytic activity with linear dose-response relationship in all of the test protocols, with ED50 values varying from 1.3 to 4.0 mg/kg i.p. The serotonin 5HT1A receptor antagonist 8-OH-DPAT also showed linear dose-response relationship in all

  6. Evidence that the anorexia induced by lipopolysaccharide is mediated by the 5-HT2C receptor.

    PubMed

    von Meyenburg, Claudia; Langhans, Wolfgang; Hrupka, Brian J

    2003-01-01

    Rats consistently reduce their food intake following injections of bacterial lipopolysaccharides (LPS). Because inhibition of serotonergic (5-HT) activity by 8-OH-DPAT (5-HT(1A) activation) attenuates LPS-induced anorexia, we conducted a series of studies to examine whether other 5-HT-receptors are involved in the mediation of peripheral LPS-induced anorexia. In all experiments, rats were injected with LPS (100 microg/kg body weight [BW] ip) at lights out (hour 0). Antagonists were administered peripherally at hour 4, shortly after the onset of anorexia, which presumably follows the enhanced cytokine production after LPS. Food intake was then recorded during the subsequent 2 h or longer. 5-HT receptor antagonists cyanopindolol and SB 224289 (5-HT(1B)), ketanserin (5-HT(2A)), RS-102221 (5-HT(2C)), and metoclopramide (5-HT(3)) failed to attenuate LPS-induced anorexia. In contrast, both ritanserin (5-HT(2A/C)-receptor antagonist) (0.5 mg/kg BW) and SB 242084 (5-HT(2C)) (0.3 mg/kg BW) attenuated LPS-induced anorexia at doses that did not alter food intake in non-LPS-treated rats (all P<.01). Our results suggest that at least part of the anorexia following peripheral LPS administration is mediated through an enhanced 5-HT-ergic activity and the 5-HT(2C) receptor.

  7. Synergistic Effect between Maternal Infection and Adolescent Cannabinoid Exposure on Serotonin 5HT1A Receptor Binding in the Hippocampus: Testing the “Two Hit” Hypothesis for the Development of Schizophrenia

    PubMed Central

    Dalton, Victoria S.; Verdurand, Mathieu; Walker, Adam; Hodgson, Deborah M.; Zavitsanou, Katerina

    2012-01-01

    Infections during pregnancy and adolescent cannabis use have both been identified as environmental risk factors for schizophrenia. We combined these factors in an animal model and looked at their effects, alone and in combination, on serotonin 5HT1A receptor binding (5HT1AR) binding longitudinally from late adolescence to adulthood. Pregnant rats were exposed to the viral mimic poly I:C on embryonic day 15. Adolescent offspring received daily injections of the cannabinoid HU210 for 14 days starting on postnatal day (PND) 35. Hippocampal and cortical 5HT1AR binding was quantified autoradiographically using [3H]8-OH-DPAT, in late adolescent (PND 55), young adult (PND 65) and adult (PND 90) rats. Descendants of poly I:C treated rats showed significant increases of 15–18% in 5HT1AR in the hippocampus (CA1) compared to controls at all developmental ages. Offspring of poly I:C treated rats exposed to HU210 during adolescence exhibited even greater elevations in 5HT1AR (with increases of 44, 29, and 39% at PNDs 55, 65, and 90). No effect of HU210 alone was observed. Our results suggest a synergistic effect of prenatal infection and adolescent cannabinoid exposure on the integrity of the serotoninergic system in the hippocampus that may provide the neurochemical substrate for abnormal hippocampal-related functions relevant to schizophrenia. PMID:23738203

  8. Pre- or postsynaptic activity of 5-HT1A compounds in mice depends on the anxiety paradigm.

    PubMed

    López-Rubalcava, C

    1996-08-01

    The purpose of the present study was to compare the contribution of pre and postsynaptic 5-HT1A receptors to the anxiolytic effects of serotonergic1A compounds in two animal models of anxiety. To this aim, the 5-HT1A ligands buspirone, ipsapirone, indorenate, and 8-OH-DPAT were tested in the burying behavior test and the avoidance exploratory behavior paradigm in control, pCPA-treated, and 5,7-DHT-lesioned mice, p-CPA and 5,7-DHT treatments did not modify the burying behavior per se, while 5-HT1A agonists produced a significant reduction in this behavior in both p-CPA- and 5,7,-DHT-lesioned animals. In the exploratory behavior paradigm, p-CPA per se but not 5,7-DHT increased the black/white transitions, interpreted as an antianxiety action. The ICV injection of 5,7-DHT blocked such effect of the 5-HT1A compounds in the avoidance exploratory behavior test. Data suggest that the effect of 5-HT1A compounds in the burying behavior test is mediated via the stimulation of postsynaptic receptors, while in the avoidance exploratory behavior paradigm these compounds act through the stimulation of the presynaptic site. Discussion is based on the differences between the animal models of anxiety.

  9. Escitalopram Ameliorates Forskolin-Induced Tau Hyperphosphorylation in HEK239/tau441 Cells.

    PubMed

    Ren, Qing-Guo; Wang, Yan-Juan; Gong, Wei-Gang; Zhou, Qi-Da; Xu, Lin; Zhang, Zhi-Jun

    2015-06-01

    To investigate the effect of escitalopram (a widely used and highly efficacious antidepressant from the SSRI class) on tau hyperphosphorylation, HEK293/tau441 cells were pretreated with 4 μM of forskolin for 2 h. Then we treated the cells with different doses of escitalopram (0, 5, 10, 20, 40, 80 μM) for 22 h. We measured the phosphorylation level of tau by Western blotting. It was shown that escitalopram could protect tau from hyperphosphorylation induced by pharmacological activation of protein kinase A (PKA) at a dose of 20, 40, and 80 μM in vitro. Interestingly, the same dose of escitalopram could also increase the level of serine-9-phosphorylated GSK-3β (inactive form) and the phosphorylation level of Akt at Ser473 (active form) with no significant change in the level of total GSK-3β and Akt. Unexpectedly, 5-hydroxytryptamine 1A receptor (5-HT1A) agonist 8-OH-DPAT did not decrease forskolin-induced tau hyperphosphorylation. Our results suggest that escitalopram can ameliorate forskolin-induced tau hyperphosphorylation, which is not through the typical 5-HT1A pathway, and Akt/GSK-3β signaling pathway is involved. These findings may support an effective role of antidepressants in the prevention of dementia associated with depression in patients.

  10. Characterization of 5-HT1D receptor binding sites in post-mortem human brain cortex.

    PubMed Central

    Martial, J; de Montigny, C; Cecyre, D; Quirion, R

    1991-01-01

    The present study provides further evidence for the presence of serotonin1D (5-HT1D) receptors in post-mortem human brain. Receptor binding parameters in temporal cortex homogenates were assessed using [3H]5-HT in the presence of 100 nM 8-OH-DPAT, 1 microM propranolol and 1 microM mesulergine to prevent labelling of the 5-HT1A, 5-HT1B and 5-HT1C sites, respectively. Under these conditions, [3H]5-HT apparently bound to a class of high affinity (Kd = 5.0 +/- 1.0 nM) low capacity (Bmax = 96 +/- 23 fmol/mg protein) sites. In competition experiments, 5-HT and 5-carboxyamidotryptamine (5-CT), as well as ergotamine, lysergic acid, sumatriptan and RU-24969 exhibited high affinity for these sites. This pharmacological profile is concordant with the ligand selectivity pattern reported for 5-HT1D receptors in other species and thus provides further evidence for its existence in human temporal cortex. In addition, the competition profile of some ligands, particularly of unlabelled 5-HT, 5-CT and ergotamine, revealed the existence of a lower affinity binding site. The latter suggests receptor heterogeneity or the presence of a lower affinity state of 5-HT1D receptors. PMID:1911737

  11. [Serotoninergic receptors and cardiovascular diseases].

    PubMed

    Hong, E; Castillo, C; Flores, E; Mercedes, F

    1994-01-01

    The seronin or 5-hydroxytryptamine (5-HT) is a biogenic amine involved in diverse physiologic and physiopathological processes in the cardiovascular system. 5-HT may lower the arterial blood pressure by an action on central 5-HT1A receptors, or may increase it by stimulation of 5-HT2 receptors located in vascular smooth muscle. It has been postulated that hypofunction of 5-HT1A receptors, or the exaggerated stimulation of 5-HT2 receptor may be associated with arterial hypertension and that agonists of the first type (indorenate or 8-OH-DPAT) or antagonists of the second type (ketanserin or pelanserin) allow the control of arterial hypertension. On the other land, ketanserin and pelanserin attenuated the hemodynamic manifestations in an experimental model of thromboembolism, suggesting that 5-HT is involved in such phenomenon. Finally, 5-HT could be related with the presence of angor pectoris during hypertension or atherosclerosis, diseases that are associated with a lesional of the vascular endothelium, a condition that favors the 5-HT induced vasoconstriction in coronary arteries.

  12. Anti-depressant-like effect of kaempferitrin isolated from Justicia spicigera Schltdl (Acanthaceae) in two behavior models in mice: evidence for the involvement of the serotonergic system.

    PubMed

    Cassani, Julia; Dorantes-Barrón, Ana María; Novales, Lilian Mayagoitia; Real, Guadalupe Alva; Estrada-Reyes, Rosa

    2014-12-19

    We evaluated the antidepressant-like effect of kaempferitrin (Km) isolated from the plant Justicia spicigera (Asteraceae), which is used in traditional medicine for relieving emotional disorders, such as "la tristeza" (sadness or dysthymia) and "el humor" (mood changes). The actions of Km were evaluated in a forced swimming test (FST) and a suspension tail test (TST) in mice. We explored the involvement of the serotonergic system and the hypothalamic-hypophysis-adrenal axis (HPA) in the antidepressant-like effect of Km. To evaluate nonspecific effects of Km on general activity, the open field test (OFT) was performed. Km at 5, 10, and 20 mg/kg induced an antidepressant-like effect. Sub-effective dose of Km (1 mg/kg) produced a synergistic effect with imipramine (6.25 mg/kg) and fluoxetine (10 mg/kg) but not with desipramine (3.12 mg/kg). Pretreatment with p-chlorophenylalanine methyl ester (PCPA), a serotonin synthesis inhibitor, N-{2-(4-(2-methoxyphenyl)-1-piperazinyl}-N-(2-pyridinyl)cyclohexecarboxamide (WAY-100635), a selective 5-HT1A receptor antagonist, and 8OH-DPAT, a selective 5-HT1A agonist, but not pindolol (10 mg/kg) blocked the anti- immobility effect induced by Km. Taken together, these results indicate that the antidepressant-like effect of Km is related to the serotonergic system, principally 5-HT1A. This effect was not related to changes in locomotor activity.

  13. Methylphenidate to adolescent rats drives enduring changes of accumbal Htr7 expression: implications for impulsive behavior and neuronal morphology.

    PubMed

    Leo, D; Adriani, W; Cavaliere, C; Cirillo, G; Marco, E M; Romano, E; di Porzio, U; Papa, M; Perrone-Capano, C; Laviola, G

    2009-04-01

    Methylphenidate (MPH) administration to adolescent rodents produces persistent region-specific changes in brain reward circuits and alterations of reward-based behavior. We show that these modifications include a marked increment of serotonin (5-hydroxy-tryptamine) receptor type 7 (Htr7) expression and synaptic contacts, mainly in the nucleus accumbens, and a reduction of basal behavioral impulsivity. We show that neural and behavioral consequences are functionally related: administration of a selective Htr7 antagonist fully counteracts the MPH-reduced impulsive behavior and enhances impulsivity when administered alone in naive rats. Agonist-induced activation of endogenous Htr7 significantly increases neurite length in striatal neuron primary cultures, thus suggesting plastic remodeling of neuronal morphology. The mixed Htr (1a/7) agonist, 8-OH-DPAT, reduces impulsive behavior in adolescent rats and in naive adults, whose impulsivity is enhanced by the Htr7 antagonist. In summary, behavioral pharmacology experiments show that Htr7 mediates self-control behavior, and brain primary cultures experiments indicate that this receptor may be involved in the underlying neural plasticity, through changes in neuronal cytoarchitecture.

  14. Peripheral 5-HT1A and 5-HT7 Serotonergic Receptors Modulate Parasympathetic Neurotransmission in Long-Term Diabetic Rats

    PubMed Central

    Restrepo, Beatriz; Martín, María Luisa; San Román, Luis; Morán, Asunción

    2010-01-01

    We analyzed the modulation of serotonin on the bradycardia induced in vivo by vagal electrical stimulation in alloxan-induced long-term diabetic rats. Bolus intravenous administration of serotonin had a dual effect on the bradycardia induced either by vagal stimulation or exogenous Ach, increasing it at low doses and decreasing it at high doses of 5-hydroxytryptamine (5-HT), effect reproduced by 5-carboxamidotryptamine maleate (5-CT), a 5-HT1/7 agonist. The enhancement of the bradycardia at low doses of 5-CT was reproduced by 5-HT1A agonist 8-hydroxy-2-dipropylaminotetralin hydrobromide (8-OH-DPAT) and abolished by WAY-100,635, 5-HT1A antagonist. Pretreatment with 5-HT1 antagonist methiothepin blocked the stimulatory and inhibitory effect of 5-CT, whereas pimozide, 5-HT7 antagonist, only abolished 5-CT inhibitory action. In conclusion, long-term diabetes elicits changes in the subtype of the 5-HT receptor involved in modulation of vagally induced bradycardia. Activation of the 5-HT1A receptors induces enhancement, whereas attenuation is due to 5-HT7 receptor activation. This 5-HT dual effect occurs at pre- and postjunctional levels. PMID:21403818

  15. Serotonergic mechanisms are necessary for central respiratory chemoresponsiveness in situ

    PubMed Central

    Corcoran, Andrea E.; Richerson, George B.; Harris, Michael B.

    2013-01-01

    Evidence from in vivo and in vitro experiments conclude that serotonin (5-HT) neurons are involved in and play an important role in central respiratory CO2/H+ chemosensitivity. This study was designed to assess the importance of 5-HT neurons and 5-HT receptor activation in the frequency and amplitude components of the hypercapnic response of the respiratory network in the unanesthetized perfused in situ juvenile rat brainstem preparation that exhibits patterns of phrenic nerve discharge similar to breathing in vivo. Exposure to a hypercapnic perfusate increased phrenic burst frequency and/or amplitude, the neural correlates of breathing frequency and tidal volume in vivo. Hypercapnic responses were also assessed during exposure to ketanserin (5-HT2 receptor antagonist), and 8-OH-DPAT (inhibiting 5-HT neurons via 5-HT1A autoreceptors). Neither of these drugs substantially altered baseline activity, however, both abolished hypercapnic responses of the respiratory network. These data illustrate that 5-HT neurons and 5-HT receptor activation are not required for respiratory rhythm generation per se, but are critical for CO2 responses in situ, supporting the hypothesis that 5-HT neurons play an important role in central ventilatory chemosensitivity in vivo. PMID:23454177

  16. Evidence for the existence of FGFR1-5-HT1A heteroreceptor complexes in the midbrain raphe 5-HT system.

    PubMed

    Borroto-Escuela, Dasiel O; Narvaez, Manuel; Pérez-Alea, Mileidys; Tarakanov, Alexander O; Jiménez-Beristain, Antonio; Mudó, Giuseppa; Agnati, Luigi F; Ciruela, Francisco; Belluardo, Natale; Fuxe, Kjell

    2015-01-02

    The ascending midbrain 5-HT neurons known to contain 5-HT1A autoreceptors may be dysregulated in depression due to a reduced trophic support. With in situ proximity ligation assay (PLA) and supported by co-location of the FGFR1 and 5-HT1A immunoreactivities in midbrain raphe 5-HT cells, evidence for the existence of FGFR1-5-HT1A heteroreceptor complexes were obtained in the dorsal and median raphe nuclei of the Sprague-Dawley rat. Their existence in the rat medullary raphe RN33B cell cultures was also established. After combined FGF-2 and 8-OH-DPAT treatment, a marked and significant increase in PLA positive clusters was found in the RN33B cells. Similar results were reached upon coactivation by agonists in HEK293T cells using the Fluorescent Resonance Energy Transfer (FRET) technique resulting in increased FRETmax and reduced FRET50 values. The heteroreceptor complex formation was dependent on TMV of the 5-HT1A receptor since it was blocked by incubation with TMV but not with TMII. Taken together, the 5-HT1A autoreceptors by being recruited into a FGFR1-5-HT1A heteroreceptor complex in the midbrain raphe 5-HT nerve cells may develop a novel function, namely a trophic role in many midbrain 5-HT neuron systems originating from the dorsal and medianus raphe nuclei.

  17. Spinal 5-HT1A, not the 5-HT1B or 5-HT3 receptors, mediates descending serotonergic inhibition for late-phase mechanical allodynia of carrageenan-induced peripheral inflammation.

    PubMed

    Kim, Joung Min; Jeong, Seong Wook; Yang, Jihoon; Lee, Seong Heon; Kim, Woon Mo; Jeong, Seongtae; Bae, Hong Beom; Yoon, Myung Ha; Choi, Jeong Il

    2015-07-23

    Previous electrophysiological studies demonstrated a limited role of 5-hydroxytryptamine 3 receptor (5-HT3R), but facilitatory role of 5-HT1AR and 5-HT1BR in spinal nociceptive processing of carrageenan-induced inflammatory pain. The release of spinal 5-HT was shown to peak in early-phase and return to baseline in late-phase of carrageenan inflammation. We examined the role of the descending serotonergic projections involving 5-HT1AR, 5-HT1BR, and 5-HT3R in mechanical allodynia of early- (first 4h) and late-phase (24h after) carrageenan-induced inflammation. Intrathecal administration of 5-HT produced a significant anti-allodynic effect in late-phase, but not in early-phase. Similarly, intrathecal 5-HT1AR agonist (8-OH-DPAT) attenuated the intensity of late-phase allodynia in a dose dependent fashion which was antagonized by 5-HT1AR antagonist (WAY-100635), but produced no effect on the early-phase allodynia. However, other agonists or antagonists of 5-HT1BR (CP-93129, SB-224289) and 5-HT3R (m-CPBG, ondansetron) did not produce any anti- or pro-allodynic effect in both early- and late- phase allodynia. These results suggest that spinal 5-HT1A, but not 5-HT1B or 5-HT3 receptors mediate descending serotonergic inhibition on nociceptive processing of late-phase mechanical allodynia in carrageenan-induced inflammation.

  18. Effects of the 5-HT7 receptor antagonists SB-269970 and DR 4004 in autoshaping Pavlovian/instrumental learning task.

    PubMed

    Meneses, Alfredo

    2004-12-06

    There is an important debate regarding the functional role of the 5-HT(1A) and 5-HT(7) receptor in memory systems. Hence, the objective of this paper is to investigate the function of serotonin (5-hydroxytryptamine, 5-HT) in memory consolidation, utilising an autoshaping Pavlovian/instrumental learning test. Specific antagonists at 5-HT(1A) (WAY 100635) and 5-HT(7) (SB-269970 or DR 4004) receptors administered i.p. or s.c.) after training, significantly decreased the improvement of performance produced by the 5-HT(1A/7) agonist 8-OH-DPAT to levels lower than controls'. These same antagonists attenuated the decreased level of performance produced by mCPP, although they decrease the performance levels after p-chloroamphetamine (PCA) lesion of the 5-HT system, which has no effect on its own on the conditioned response. Moreover, SB-269970 or DR 4004 reversed amnesia induced by scopolamine and dizocilpine. These data confirm a role for 5-HT(1A) and 5-HT(7) receptors in memory formation and support the hypothesis that serotonergic, cholinergic, and glutamatergic systems interact in cognitively impaired animals. These findings support a potential role for both 5-HT(1A) and 5-HT(7) receptors in the pathophysiology and/or treatment of schizophrenia, cognitive deficits and the mechanism of action of atypical antipsychotic drugs.

  19. Role of dorsal raphe nucleus 5-HT(1A) and 5-HT(2) receptors in tonic immobility modulation in guinea pigs.

    PubMed

    Ferreira, Mateus Dalbem; Menescal-de-Oliveira, Leda

    2009-08-18

    Tonic immobility (TI) is an innate defensive behavior characterized by a state of physical inactivity and diminished responsiveness to environmental stimuli. Behavioral adaptations to changes in the external and internal milieu involve complex neuronal network activity and a large number of chemical neurotransmitters. The TI response is thought to be influenced by serotonin (5-HT) activity in the central nervous system (CNS) of vertebrates, but the neuronal groups involved in the mechanisms underlying this behavior are poorly understood. Owing to its extensive afferents and efferents, the dorsal raphe nucleus (DRN) has been implicated in a great variety of physiological and behavioral functions. In the current study, we investigated the influence of serotonergic 5-HT(1A) and 5-HT(2) receptor activity within the DRN on the modulation of TI behavior in the guinea pig. Microinjection of a 5-HT(1A) receptor agonist (8-OH-DPAT, 0.01 and 0.1 microg) decreased TI behavior, an effect blocked by pretreatment with WAY-100635 (0.033 microg), a 5-HT(1A) antagonist. In contrast, activation of 5-HT(2) receptors within the DRN (alpha-methyl-5-HT, 0.5 microg) increased the TI duration, and this effect could be reversed by pretreatment with an ineffective dose (0.01 microg) of ketanserine. Since the 5-HT(1A) and 5-HT(2) agonists decreased and increased, respectively, the duration of TI, different serotonin receptor subtypes may play distinct roles in the modulation of TI in the guinea pig.

  20. Serotonin regulates brain-derived neurotrophic factor expression in select brain regions during acute psychological stress

    PubMed Central

    Jiang, De-guo; Jin, Shi-li; Li, Gong-ying; Li, Qing-qing; Li, Zhi-ruo; Ma, Hong-xia; Zhuo, Chuan-jun; Jiang, Rong-huan; Ye, Min-jie

    2016-01-01

    Previous studies suggest that serotonin (5-HT) might interact with brain-derived neurotrophic factor (BDNF) during the stress response. However, the relationship between 5-HT and BDNF expression under purely psychological stress is unclear. In this study, one hour before psychological stress exposure, the 5-HT1A receptor agonist 8-OH-DPAT or antagonist MDL73005, or the 5-HT2A receptor agonist DOI or antagonist ketanserin were administered to rats exposed to psychological stress. Immunohistochemistry and in situ hybridization revealed that after psychological stress, with the exception of the ventral tegmental area, BDNF protein and mRNA expression levels were higher in the 5-HT1A and the 5-HT2A receptor agonist groups compared with the solvent control no-stress or psychological stress group in the CA1 and CA3 of the hippocampus, prefrontal cortex, central amygdaloid nucleus, dorsomedial hypothalamic nucleus, dentate gyrus, shell of the nucleus accumbens and the midbrain periaqueductal gray. There was no significant difference between the two agonist groups. In contrast, after stress exposure, BDNF protein and mRNA expression levels were lower in the 5-HT1A and 5-HT2A receptor antagonist groups than in the solvent control non-stress group, with the exception of the ventral tegmental area. Our findings suggest that 5-HT regulates BDNF expression in a rat model of acute psychological stress. PMID:27857753

  1. Circadian rhythms of clock gene expression in the cerebellum of serotonin-deficient Pet-1 knockout mice.

    PubMed

    Paulus, Erin V; Mintz, Eric M

    2016-01-01

    Serotonin plays an important role in the central regulation of circadian clock function. Serotonin levels are generally higher in the brain during periods of high activity, and these periods are in turn heavily regulated by the circadian clock located in the suprachiasmatic nucleus. However, the role of serotonin as a regulator of circadian rhythms elsewhere in the brain has not been extensively examined. In this study, we examined circadian rhythms of clock gene expression in the cerebellum in mice lacking the Pet-1 transcription factor, which results in a developed brain that is deficient in serotonin neurons. If serotonin helps to synchronize rhythms in brain regions other than the suprachiasmatic nucleus, we would expect to see differences in clock gene expression in these serotonin deficient mice. We found minor differences in the expression of Per1 and Per2 in the knockout mice as compared to wild type, but these differences were small and of questionable functional importance. We also measured the response of cerebellar clocks to injections of the serotonin agonist 8-OH-DPAT during the early part of the night. No effect on clock genes was observed, though the immediate-early gene Fos showed increased expression in wild type mice but not the knockouts. These results suggest that serotonin is not an important mediator of circadian rhythms in the cerebellum in a way that parallels its regulation of the circadian clock in the suprachiasmatic nucleus.

  2. Chronic imipramine enhances 5-HT(1A) and 5-HT(2) receptors-mediated inhibition of panic-like behavior in the rat dorsal periaqueductal gray.

    PubMed

    Jacob, Cláudia A; Cabral, Alfredo H C L; Almeida, Leandro P; Magierek, Valeska; Ramos, Patrício L; Zanoveli, Janaína M; Landeira-Fernandez, Jesus; Zangrossi, Hélio; Nogueira, Regina L

    2002-07-01

    Electrical stimulation of the dorsal periaqueductal gray (DPAG) has been used to induce panic-like behavior in rats. In the present study, we investigated the effect of chronic imipramine treatment on the sensitivity of different 5-HT receptor subtypes in inhibiting aversion induced by electrical stimulation of this brain area. For that, the effects of intra-DPAG administration of the endogenous agonist 5-HT (20 nmol), the 5-HT(1A) receptor agonist 8-OH-DPAT (8 nmol) and the 5-HT(2A/2C) receptor agonist DOI (16 nmol) were measured in female Wistar rats given either chronic injection of imipramine (15 mg/kg, 3 weeks, ip) or saline. The results showed that the three receptor agonists raised the threshold of aversive electrical stimulation in both groups of animals, but this antiaversive effect was significantly higher in rats treated with imipramine. Treatment with imipramine did not change the basal threshold of aversive electrical stimulation measured before intra-DPAG injection of the 5-HT agonists. The results suggest that sensitization of both 5-HT(1A) and 5-HT(2) receptors within the DPAG may be involved in the beneficial effect of imipramine in panic disorder (PD).

  3. The psychostimulant d-threo-(R,R)-methylphenidate binds as an agonist to the 5HT(1A) receptor.

    PubMed

    Markowitz, J S; DeVane, C L; Ramamoorthy, S; Zhu, Hao-Jie

    2009-02-01

    The present study was undertaken to determine whether d-threo-(R,R)-methylphenidate (MPH) was exerting binding activity as an agonist or antagonist of 5-HT1A and 5-HT2B receptors. [35S]guanosine5'[gamma-thio]triphosphate ([35S]GTPgammaS) binding assay and field-stimulated Guinea pig ileum assay were used to determine 5-HT(1A) receptor agonism and antagonism activity of d-threo-(R,R)-MPH. The results suggested d-threo-(R,R)-MPH induced 5-HT(1A) receptor agonist activity at 100 microM. The Guinea pig ileum functional assay showed that d-threo-(R,R)-MPH produced agonist-like reduction of neurogenic twitch with an EC50 5.65 +/- 0.36 microM. At 30 microM concentrations, d-threo-(R,R)-MPH produced 171 +/- 4.24% of the relaxation relative to that caused by 0.12 microM 8-OH-DPAT. However, d-threo-(R,R)-MPH exhibited no significant pharmacological activity in rat stomach fundus 5-HT(2B) receptor functional assay. Thus, d-threo-(R,R)-MPH appears to act as a selective 5-HT(1A) receptor agonist in vitro. It is speculated that the activation of 5-HT(1A) receptor might play a partial role in d-threo-(R,R)-MPH mediated dopamine (DA) release in the brain.

  4. The role of the dorsal raphe nucleus in the development, expression, and treatment of L-dopa-induced dyskinesia in hemiparkinsonian rats.

    PubMed

    Eskow, Karen L; Dupre, Kristin B; Barnum, Christopher J; Dickinson, Sando O; Park, John Y; Bishop, Christopher

    2009-07-01

    Convergent evidence indicates that in later stages of Parkinson's disease raphestriatal serotonin neurons compensate for the loss of nigrostriatal dopamine neurons by converting and releasing dopamine derived from exogenous administration of the pharmacotherapeutic L-3,4-dihydroxyphenyl-L-alanine (L-dopa). Because the serotonin system is not equipped with dopamine autoregulatory mechanisms, it has been postulated that raphe-mediated striatal dopamine release may fluctuate dramatically. These fluctuations may portend the development of abnormal involuntary movements called L-dopa-induced dyskinesia (LID). As such, it has been hypothesized that reducing the activity of raphestriatal neurons could dampen supraphysiological stimulation of striatal dopamine receptors thereby alleviating LID. To directly address this, the current study employed the rodent model of LID to investigate the contribution of the rostral raphe nuclei (RRN) in the development, expression and treatment of LID. In the first study, dual serotonin/dopamine selective lesions of the RRN and medial forebrain bundle, respectively, verified that the RRN are essential for the development of LID. In a direct investigation into the neuroanatomical specificity of these effects, microinfusions of +/-8-OH-DPAT into the intact dorsal raphe nucleus dose-dependently attenuated the expression of LID without affecting the antiparkinsonian efficacy of L-dopa. These current findings reveal the integral contribution of the RRN in the development and expression of LID and implicate a prominent role for dorsal raphe 5-HT1AR in the efficacious properties of 5-HT1AR agonists.

  5. The role of the dorsal raphe nucleus in the development, expression and treatment of LID in hemiparkinsonian rats

    PubMed Central

    Eskow, Karen L.; Dupre, Kristin B.; Barnum, Christopher J.; Dickinson, Sando O.; Park, John Y.; Bishop, Christopher

    2009-01-01

    Convergent evidence indicates that in later stages of Parkinson's disease raphestriatal serotonin neurons compensate for the loss of nigrostriatal dopamine neurons by converting and releasing dopamine derived from exogenous administration of the pharmacotherapeutic L-3,4-dihydroxyphenyl-L-alanine (L-DOPA). Because the serotonin system is not equipped with dopamine autoregulatory mechanisms, it has been postulated that raphe-mediated striatal dopamine release may fluctuate dramatically. These fluctuations may portend the development of abnormal involuntary movements called L-DOPA-induced dyskinesia (LID). As such, it has been hypothesized that reducing the activity of raphestriatal neurons could dampen supraphysiological stimulation of striatal dopamine receptors thereby alleviating LID. To directly address this, the current study employed the rodent model of LID to investigate the contribution of the rostral raphe nuclei (RRN) in the development, expression and treatment of LID. In the first study, dual serotonin/dopamine selective lesions of the RRN and medial forebrain bundle, respectively, verified that the RRN are essential for the development of LID. In a direct investigation into the neuroanatomical specificity of these effects, microinfusions of ±8-OH-DPAT into the intact dorsal raphe nucleus dose-dependently attenuated the expression of LID without affecting the anti-parkinsonian efficacy of L-DOPA. These current findings reveal the integral contribution of the RRN in the development and expression of LID and implicate a prominent role for dorsal raphe 5-HT1AR in the efficacious properties of 5-HT1AR agonists. PMID:19309758

  6. Serotonin decreases aggression via 5-HT1A receptors in the fighting fish Betta splendens.

    PubMed

    Clotfelter, Ethan D; O'Hare, Erin P; McNitt, Meredith M; Carpenter, Russ E; Summers, Cliff H

    2007-01-01

    The role of the monoamine neurotransmitter serotonin (5-HT) in the modulation of conspecific aggression in the fighting fish (Betta splendens) was investigated using pharmacological manipulations. We used a fish's response to its mirror image as our index of aggressive behavior. We also investigated the effects of some manipulations on monoamine levels in the B. splendens brain. Acute treatment with 5-HT and with the 5-HT1A receptor agonist 8-OH-DPAT both decreased aggressive behavior; however, treatment with the 5-HT1A receptor antagonist WAY-100635 did not increase aggression. Chronic treatment with the selective serotonin reuptake inhibitor fluoxetine caused no significant changes in aggressive behavior and a significant decline in 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) concentrations. Treatment with the serotonin synthesis inhibitor p-chlorophenylalanine resulted in no change in aggression, yet serotonergic activity decreased significantly. Finally, a diet supplemented with L-tryptophan (Trp), the precursor to 5-HT, showed no consistent effects on aggressive behavior or brain monoamine concentrations. These results suggest a complex role for serotonin in the expression of aggression in teleost fishes, and that B. splendens may be a useful model organism in pharmacological and toxicological studies.

  7. Serotonin regulates brain-derived neurotrophic factor expression in select brain regions during acute psychological stress.

    PubMed

    Jiang, De-Guo; Jin, Shi-Li; Li, Gong-Ying; Li, Qing-Qing; Li, Zhi-Ruo; Ma, Hong-Xia; Zhuo, Chuan-Jun; Jiang, Rong-Huan; Ye, Min-Jie

    2016-09-01

    Previous studies suggest that serotonin (5-HT) might interact with brain-derived neurotrophic factor (BDNF) during the stress response. However, the relationship between 5-HT and BDNF expression under purely psychological stress is unclear. In this study, one hour before psychological stress exposure, the 5-HT1A receptor agonist 8-OH-DPAT or antagonist MDL73005, or the 5-HT2A receptor agonist DOI or antagonist ketanserin were administered to rats exposed to psychological stress. Immunohistochemistry and in situ hybridization revealed that after psychological stress, with the exception of the ventral tegmental area, BDNF protein and mRNA expression levels were higher in the 5-HT1A and the 5-HT2A receptor agonist groups compared with the solvent control no-stress or psychological stress group in the CA1 and CA3 of the hippocampus, prefrontal cortex, central amygdaloid nucleus, dorsomedial hypothalamic nucleus, dentate gyrus, shell of the nucleus accumbens and the midbrain periaqueductal gray. There was no significant difference between the two agonist groups. In contrast, after stress exposure, BDNF protein and mRNA expression levels were lower in the 5-HT1A and 5-HT2A receptor antagonist groups than in the solvent control non-stress group, with the exception of the ventral tegmental area. Our findings suggest that 5-HT regulates BDNF expression in a rat model of acute psychological stress.

  8. Evidence for the involvement of central serotonin in mechanism of domestication of silver foxes.

    PubMed

    Popova, N K; Voitenko, N N; Kulikov, A V; Avgustinovich, D F

    1991-12-01

    Silver foxes selected for more than 30 years for tame behavior and displaying no defensive reaction to human contact were shown to have a higher serotonin level in midbrain and hypothalamus, and a higher 5-hydroxyindole acetic acid (5-HIAA) content in midbrain, hypothalamus and hippocampus in comparison to nonselected wild silver foxes bred in captivity over the same time span. Tryptophan hydroxylase (TPH) activity in midbrain and hypothalamus in domesticated foxes was increased as compared with their aggressive/defensive counterparts. Monoamine oxidase type A (MAO A) activity was was decreased with an increased Km and unchanged Vmax in domesticated foxes. No changes in specific [3H]ketanserin or [3H]8-OH-DPAT binding in frontal cortex was revealed. A reduced density (Bmax) of 5HT1A receptors in hypothalamic membranes in domesticated foxes was shown. It is suggested that the brain serotonergic system is involved in the mechanism of domestication converting wild aggressive/defensive animals into tame ones.

  9. Contribution to the benchmark for ternary mixtures: Measurement of the Soret and thermodiffusion coefficients of tetralin+isobutylbenzene+n-dodecane at a composition of (0.8/0.1/0.1) mass fractions by two-color optical beam deflection.

    PubMed

    Gebhardt, M; Köhler, W

    2015-04-01

    Within the framework of an international benchmark test we have performed measurements of the Soret and thermodiffusion coefficients of the organic ternary mixture (0.8/0.1/0.1 mass fraction) of 1,2,3,4-tetrahydronaphthaline (THN), isobutylbenzene (IBB) and n -dodecane (n C12) at 298.15K by means of a two-color optical beam deflection technique (OBD). The data evaluation procedure is based on a least squares fitting routine for an approximate analytical solution for the Soret cell problem. The condition number of the contrast factor matrix and standard error propagation are used for an error estimation for the measured Soret and thermodiffusion coefficients. The Soret coefficients obtained are S (') T(THN) = (1.20±0.09)×10(-3) K^-1, S (') T(IBB) = (- 0.34±0.14)×10(-3) K^-1, and S (') T(nC12) = (- 0.86±0.06)×10(-3) K^-1 and the corresponding thermodiffusion coefficients are D (') T(THN) = (0.72±0.26)×10(-12) m^2(s K)^-1, D (') T(IBB) = (- 0.22±0.42)×10(-12) m^2(s K)^-1, and D (') T(nC12) = (- 0.50±0.16)×10(-12) m^2(s K)^-1. These results will be used as ground-based reference data for the DCMIX project, where thermodiffusion experiments of ternary mixtures are measured in a microgravity environment aboard the International Space Station (ISS).

  10. N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-nitrophenyl) cyclohexanecarboxamide: a novel pre- and postsynaptic 5-hydroxytryptamine(1A) receptor antagonist active on the lower urinary tract.

    PubMed

    Leonardi, A; Guarneri, L; Poggesi, E; Angelico, P; Velasco, C; Cilia, A; Testa, R

    2001-12-01

    N-[2-[4-(2-Methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-nitrophenyl) cyclohexanecarboxamide (Rec 15/3079) was synthesized with the aim of obtaining a novel compound with 5-hydroxytryptamine (5-HT)(1A) antagonistic properties and activity in controlling bladder function at the level of the central nervous system. Rec 15/3079 showed a selective high affinity for the 5-HT(1A) receptor (K(i) = 0.2 nM). At the human recombinant 5-HT(1A) receptor, Rec 15/3079 acted as a competitive, neutral antagonist in that it did not modify basal [(35)S]guanosine-5'-O-(3-thio)triphosphate binding to HeLa cell membranes but shifted the activation isotherm to 5-HT to the right, in a parallel manner, with a pK(b) value of 10.5. Accordingly, Rec 15/3079 (i.v.) potently antagonized 8-hydroxy-2-dipropylaminotetralin (8-OH-DPAT)-induced hypothermia in mice (ID(50) = 20 microg/kg) and 8-OH-DPAT-induced forepaw treading in rats (ID(50) = 36 microg/kg). In vitro Rec 15/3079 was poorly active in antagonizing carbachol-induced bladder (pD'(2) = 5.03) and norepinephrine-induced urethral (apparent pK(b) = 6) contractions. However, in anesthetized rats, Rec 15/3079 (10-100 microg/kg i.v.) blocked isovolumic bladder contractions with no effect on their amplitude. In conscious rats and guinea pigs with bladders filled with saline, Rec 15/3079 (300-1000 microg/kg i.v.) increased bladder volume capacity (BVC) without affecting bladder contractility. In conscious rats with bladders filled with dilute acetic acid, Rec 15/3079 (300 microg/kg i.v.) reversed the decrease of BVC induced by the acid. To evaluate apparent selective effect on lower urinary tract reflexes, Rec 15/3079 was tested in experimental models for sedative, analgesic, anxiolytic, and antidepressant activity. Rec 15/3079 showed only a slight decrease in the duration of immobility in the behavioral despair test (antidepressant activity) at 1 mg/kg i.v. No anxiolytic activity was observed at 10 mg/kg i.v. No effect was observed in the hot plate

  11. Serotonergic modulation of neurotransmission in the rat basolateral amygdala.

    PubMed

    Rainnie, D G

    1999-07-01

    Whole cell patch-clamp recordings were obtained from projection neurons and interneurons of the rat basolateral amygdala (BLA) to understand local network interactions in morphologically identified neurons and their modulation by serotonin. Projection neurons and interneurons were characterized morphologically and electrophysiologically according to their intrinsic membrane properties and synaptic characteristics. Synaptic activity in projection neurons was dominated by spontaneous inhibitory postsynaptic currents (IPSCs) that were multiphasic, reached 181 +/- 38 pA in amplitude, lasted 296 +/- 27 mS, and were blocked by the GABAA receptor antagonist, bicuculline methiodide (30 microM). In interneurons, spontaneous synaptic activity was characterized by a burst-firing discharge patterns (200 +/- 40 Hz) that correlated with the occurrence of 6-cyano-7-nitroquinoxaline-2,3-dione-sensitive, high-amplitude (260 +/- 42 pA), long-duration (139 +/- 19 mS) inward excitatory postsynaptic currents (EPSCs). The interevent interval of 831 +/- 344 mS for compound inhibitory postsynaptic potentials (IPSPs), and 916 +/- 270 mS for EPSC bursts, suggested that spontaneous IPSP/Cs in projection neurons are driven by burst of action potentials in interneurons. Hence, BLA interneurons may regulate the excitability of projection neurons and thus determine the degree of synchrony within ensembles of BLA neurons. In interneurons 5-hydroxytryptamine oxalate (5-HT) evoked a direct, dose-dependent, membrane depolarization mediated by a 45 +/- 6.9 pA inward current, which had a reversal potential of -90 mV. The effect of 5-HT was mimicked by the 5-HT2 receptor agonist, alpha-methyl-5-hydroxytryptamine (alpha-methyl-5-HT), but not by the 5-HT1A receptor agonist, (+/-) 8-hydroxydipropylaminotetralin hydrobromide (8-OH-DPAT), or the 5-HT1B agonist, CGS 12066A. In projection neurons, 5-HT evoked an indirect membrane hyperpolarization ( approximately 2 mV) that was associated with a 75 +/- 42 p

  12. Deletion of GIRK2 Subunit of GIRK Channels Alters the 5-HT1A Receptor-Mediated Signaling and Results in a Depression-Resistant Behavior

    PubMed Central

    Llamosas, Nerea; Bruzos-Cidón, Cristina; Rodríguez, José Julio; Ugedo, Luisa

    2015-01-01

    Background: Targeting dorsal raphe 5-HT1A receptors, which are coupled to G-protein inwardly rectifying potassium (GIRK) channels, has revealed their contribution not only to behavioral and functional aspects of depression but also to the clinical response to its treatment. Although GIRK channels containing GIRK2 subunits play an important role controlling excitability of several brain areas, their impact on the dorsal raphe activity is still unknown. Thus, the goal of the present study was to investigate the involvement of GIRK2 subunit-containing GIRK channels in depression-related behaviors and physiology of serotonergic neurotransmission. Methods: Behavioral, functional, including in vivo extracellular recordings of dorsal raphe neurons, and neurogenesis studies were carried out in wild-type and GIRK2 mutant mice. Results: Deletion of the GIRK2 subunit promoted a depression-resistant phenotype and determined the behavioral response to the antidepressant citalopram without altering hippocampal neurogenesis. In dorsal raphe neurons of GIRK2 knockout mice, and also using GIRK channel blocker tertiapin-Q, the basal firing rate was higher than that obtained in wild-type animals, although no differences were observed in other firing parameters. 5-HT1A receptors were desensitized in GIRK2 knockout mice, as demonstrated by a lower sensitivity of dorsal raphe neurons to the inhibitory effect of the 5-HT1A receptor agonist, 8-OH-DPAT, and the antidepressant citalopram. Conclusions: Our results indicate that GIRK channels formed by GIRK2 subunits determine depression-related behaviors as well as basal and 5-HT1A receptor-mediated dorsal raphe neuronal activity, becoming alternative therapeutic targets for psychiatric diseases underlying dysfunctional serotonin transmission. PMID:25956878

  13. Bidirectional amygdaloid control of neuropathic hypersensitivity mediated by descending serotonergic pathways acting on spinal 5-HT3 and 5-HT1A receptors.

    PubMed

    Sagalajev, B; Bourbia, N; Beloushko, E; Wei, H; Pertovaara, A

    2015-04-01

    Amygdala is involved in processing of primary emotions and particularly its central nucleus (CeA) also in pain control. Here we studied mechanisms mediating the descending control of mechanical hypersensitivity by the CeA in rats with a peripheral neuropathy in the left hind limb. For drug administrations, the animals had a guide cannula in the right CeA and an intrathecal catheter or another guide cannula in the medullary raphe. Hypersensitivity was tested with monofilaments. Glutamate administration in the CeA produced a bidirectional effect on hypersensitivity that varied from an increase at a low-dose (9μg) to a reduction at high doses (30-100μg). The increase but not the reduction of hypersensitivity was prevented by blocking the amygdaloid NMDA receptor with a dose of MK-801 that alone had no effects. The glutamate-induced increase in hypersensitivity was reversed by blocking the spinal 5-HT3 receptor with ondansetron, whereas the reduction in hypersensitivity was reversed by blocking the spinal 5-HT1A receptor with WAY-100635. Both the increase and decrease of hypersensitivity induced by amygdaloid glutamate treatment were reversed by medullary administration of a 5-HT1A agonist, 8-OH-DPAT, that presumably produced autoinhibition of serotonergic cell bodies in the medullary raphe. The results indicate that depending on the dose, glutamate in the CeA has a descending facilitatory or inhibitory effect on neuropathic pain hypersensitivity. Serotoninergic raphe neurons are involved in mediating both of these effects. Spinally, the 5-HT3 receptor contributes to the increase and the 5-HT1A receptor to the decrease of neuropathic hypersensitivity induced by amygdaloid glutamate.

  14. 5-HT2A receptor activation is necessary for CO2-induced arousal

    PubMed Central

    Smith, Haleigh R.; MacAskill, Amanda; Richerson, George B.

    2015-01-01

    Hypercapnia-induced arousal from sleep is an important protective mechanism pertinent to a number of diseases. Most notably among these are the sudden infant death syndrome, obstructive sleep apnea and sudden unexpected death in epilepsy. Serotonin (5-HT) plays a significant role in hypercapnia-induced arousal. The mechanism of 5-HT's role in this protective response is unknown. Here we sought to identify the specific 5-HT receptor subtype(s) involved in this response. Wild-type mice were pretreated with antagonists against 5-HT receptor subtypes, as well as antagonists against adrenergic, cholinergic, histaminergic, dopaminergic, and orexinergic receptors before challenge with inspired CO2 or hypoxia. Antagonists of 5-HT2A receptors dose-dependently blocked CO2-induced arousal. The 5-HT2C receptor antagonist, RS-102221, and the 5-HT1A receptor agonist, 8-OH-DPAT, attenuated but did not completely block CO2-induced arousal. Blockade of non-5-HT receptors did not affect CO2-induced arousal. None of these drugs had any effect on hypoxia-induced arousal. 5-HT2 receptor agonists were given to mice in which 5-HT neurons had been genetically eliminated during embryonic life (Lmx1bf/f/p) and which are known to lack CO2-induced arousal. Application of agonists to 5-HT2A, but not 5-HT2C, receptors, dose-dependently restored CO2-induced arousal in these mice. These data identify the 5-HT2A receptor as an important mediator of CO2-induced arousal and suggest that, while 5-HT neurons can be independently activated to drive CO2-induced arousal, in the absence of 5-HT neurons and endogenous 5-HT, 5-HT receptor activation can act in a permissive fashion to facilitate CO2-induced arousal via another as yet unidentified chemosensor system. PMID:25925320

  15. 5-HT1D receptor inhibits renal sympathetic neurotransmission by nitric oxide pathway in anesthetized rats.

    PubMed

    García-Pedraza, José-Ángel; García, Mónica; Martín, María-Luisa; Morán, Asunción

    2015-09-01

    Although serotonin has been shown to inhibit peripheral sympathetic outflow, serotonin regulation on renal sympathetic outflow has not yet been elucidated. This study investigated which 5-HT receptor subtypes are involved. Wistar rats were anesthetized (sodium pentobarbital; 60mg/kg, i.p.), and prepared for in situ autoperfused rat kidney, which allows continuous measurement of systemic blood pressure (SBP), heart rate (HR) and renal perfusion pressure (PP). Electrical stimulation of renal sympathetic nerves resulted in frequency-dependent increases in PP (18.3±1.0, 43.7±2.7 and 66.7±4.0 for 2, 4 and 6Hz, respectively), without altering SBP or HR. 5-HT, 5-carboxamidotryptamine (5-HT1/7 agonist) (0.00000125-0.1μg/kg each) or l-694,247 (5-HT1D agonist; 0.0125μg/kg) i.a. bolus inhibited vasopressor responses by renal nerve electrical stimulation, unlike i.a. bolus of agonists α-methyl-5-HT (5-HT2), 1-PBG (5-HT3), cisapride (5-HT4), AS-19 (5-HT7), CGS-12066B (5-HT1B) or 8-OH-DPAT (5-HT1A) (0.0125μg/kg each). The effect of l-694,247 did not affect the exogenous norepinephrine-induced vasoconstrictions, whereas was abolished by antagonist LY310762 (5-HT1D; 1mg/kg) or l-NAME (nitric oxide; 10mg/kg), but not by indomethacin (COX1/2; 2mg/kg) or glibenclamide (ATP-dependent K(+) channel; 20mg/kg). These results suggest that 5-HT mechanism-induced inhibition of rat vasopressor renal sympathetic outflow is mainly mediated by prejunctional 5-HT1D receptors via nitric oxide release.

  16. 5-HT2 receptor blockade exhibits 5-HT vasodilator effects via nitric oxide, prostacyclin and ATP-sensitive potassium channels in rat renal vasculature.

    PubMed

    García-Pedraza, J A; García, M; Martín, M L; Rodríguez-Barbero, A; Morán, A

    2016-04-01

    The aim of this study was to determine whether orally sarpogrelate (selective 5-HT2 antagonist) treatment (30 mg/kg/day; 14 days) could modify 5-HT renal vasoconstrictor responses, characterizing 5-HT receptors and mediator mechanisms involved in serotonergic responses in the in situ autoperfused rat kidney. Intra-arterial (i.a.) injections of 5-HT (0.00000125 to 0.1 μg/kg) decreased renal perfusion pressure (RPP) but did not affect the mean blood pressure (MBP). i.a. agonists 5-CT (5-HT1/7), CGS-12066B (5-HT1B), L-694,247 (5-HT1D) or AS-19 (5-HT7) mimicked renal 5-HT vasodilator effect. However, neither 8-OH-DPAT (5-HT1A) nor 1-phenylbiguanide (5-HT3) modified RPP. Moreover: (i) GR-55562 (5-HT1B antagonist) and L-NAME (nitric oxide synthase [NOS] inhibitor) blocked CGS-12066B-induced vasodilator response, (ii) LY310762 (5-HT1D antagonist) and indomethacin (non-selective cyclooxygenase inhibitor) blocked L-694,247-induced vasodilator response; (iii) SB-258719 (5-HT7 antagonist) and glibenclamide (ATP-sensitive K+ channel blocker) blocked AS-19-induced vasodilator response; and (iv) 5-HT- or 5-CT-elicited renal vasodilation was significantly blocked by the mixture of GR-55562 + LY310762 + SB-258719. Furthermore, eNOS and iNOS proteins and prostacyclin levels are overexpressed in sarpogrelate-treated rats. Our data suggest that 5-HT exerts renal vasodilator effect in the in situ autoperfused sarpogrelate-treated rat kidney, mediated by 5-HT1D, 5-HT1B and 5-HT7 receptors, involving cyclooxygenase-derived prostacyclin, nitric oxide synthesis/release and ATP-sensitive K+ channels, respectively.

  17. Contractile 5-HT1 receptors in human isolated pial arterioles: correlation with 5-HT1D binding sites.

    PubMed Central

    Hamel, E.; Bouchard, D.

    1991-01-01

    1. The 5-hydroxytryptamine (5-HT) receptor responsible for inducing vasoconstriction in human isolated pial arterioles has been pharmacologically characterized. 2. Of several 5-HT agonists tested, 5-carboxamidotryptamine (5-CT) was the most potent and the rank order of agonist potency can be summarized as: 5-CT greater than 5-HT greater than RU 24969 = alpha-methyl-5-HT = methysergide much greater than MDL 72832 = 2-methyl-5-HT much greater than 2-dipropylamino-8-hydroxy-1,2,3,4-tetrahydro-naphthalene (8-OH-DPAT). With few exceptions, the maximal contractile responses of these agonists were comparable to that induced by 5-HT. 3. A correlation analysis performed between the agonists vascular potency (pD2 values) and their affinities (pKD values) published at various subtypes of 5-HT binding sites showed a positive significant correlation with rat cortical 5-HT1B (r = 0.86; P less than 0.01) and human caudate 5-HT1D (r = 0.98; P less than 0.005) subtypes. 4. Selective antagonists at 5-HT2 (ketanserin, mianserin, MDL 11939) and 5-HT3 (MDL 72222) sites were totally devoid of inhibitory activity on the 5-HT-induced contraction, an observation which agreed with the agonist data and further excluded activation of these receptors. In contrast, the 5-HT1-like/5-HT2 antagonist methiothepin and the non-selective 5-HT1D compound metergoline inhibited with high affinity the contraction induced by 5-HT with respective pA2 values of 8.55 +/- 0.16 and 6.88 +/- 0.05. This contractile response was, however, insensitive to 5-HT1B (propranolol) and 5-HT1C (mesulergine, mianserin) antagonists.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2043924

  18. Identification of 5-hydroxytryptamine1D binding sites in sheep caudate nucleus membranes.

    PubMed

    Pauwels, P J; Palmier, C; Briley, M

    1993-08-03

    Radioligand binding measurements were performed in membranes of sheep caudate nucleus using [3H]5-hydroxytryptamine (5-HT). [3H]5-HT labeled a population of high affinity binding sites with a Kd of 1.9 +/- 0.1 nM and a Bmax of 19.8 +/- 2.2 fmol/mg tissue. Combined 5-HTID/E binding sites were the predominant 5-HT1 subtype, accounting for 78% of the total population of 5-HT1 binding sites. 5-Carboxamidotryptamine (5-CT) and sumatriptan yielded inhibition curves which best fitted a two-site model with high affinity values of 0.8 and 10.1 nM, and 1000 and 206 nM for their low affinity components. The proportion of the high affinity 5-CT and sumatriptan binding sites was 79 and 72%. The binding affinity profile of 5-HT1D binding sites [5-CT > 5-HT > d-LSD > 5-MeOT > sumatriptan > RU 24,969 > metergoline > tryptamine = rauwolscine = methylsergide > yohimbine = methiothepin > TFMPP = 8-OH-DPAT > 2-methyl-5-HT > mCPP = quipazine = CP 93,129 > ketanserin > (-)-propranolol = haloperidol = ipsapirone] compares well to that reported for 5-HT1D receptor sites in human caudate and cortex (correlation coefficient: 0.99 and 0.98). The present results indicate that sheep caudate nucleus is a valid tissue for studying interaction of compounds with 5-HT1D binding sites in the relative absence of 5-HT1E binding sites.

  19. Alterations of 5-HT1A receptor-induced G-protein functional activation and relationship to memory deficits in patients with pharmacoresistant temporal lobe epilepsy.

    PubMed

    Cuellar-Herrera, Manola; Velasco, Ana Luisa; Velasco, Francisco; Trejo, David; Alonso-Vanegas, Mario; Nuche-Bricaire, Avril; Vázquez-Barrón, Daruni; Guevara-Guzmán, Rosalinda; Rocha, Luisa

    2014-12-01

    The 5-hydroxytryptamine-1A (5-HT1A) receptors are known to be involved in the inhibition of seizures in epilepsy. Moreover, studies propose a role for the 5-HT1A receptor in memory function; it is believed that the higher density of this receptor in the hippocampus plays an important role in its regulation. Positron emission tomography (PET) studies in patients with mesial temporal lobe epilepsy (mTLE) have demonstrated that a decrease in 5-HT1A receptor binding in temporal regions may play a role in memory impairment. The evidences lead us to speculate whether this decrease in receptor binding is associated with a reduced receptor number or if the functionality of the 5-HT1A receptor-induced G-protein activation and/or the second messenger cascade is modified. The purpose of the present study is to determine 5-HT1A receptor-induced G-protein functional activation by 8-OH-DPAT-stimulated [(35)S]GTPγS binding assay in hippocampal tissue of surgical patients with mTLE. We correlate functional activity with epilepsy history and neuropsychological assessment of memory. We found that maximum functional activation stimulation values (Emax) of [(35)S]GTPγS binding were significantly increased in mTLE group when compared to autopsy samples. Furthermore, significant correlations were found: (1) positive coefficients between the Emax with the age of patient and frequency of seizures; (2) negative coefficients between the Emax and working memory, immediate recall and delayed recall memory tasks. Our data suggest that the epileptic hippocampus of patients with mTLE presents an increase in 5-HT1A receptor-induced G-protein functional activation, and that this altered activity is related to age and seizure frequency, as well as to memory consolidation deficit.

  20. Phencyclidine-induced disruption of oscillatory activity in prefrontal cortex: Effects of antipsychotic drugs and receptor ligands.

    PubMed

    Lladó-Pelfort, L; Troyano-Rodriguez, E; van den Munkhof, H E; Cervera-Ferri, A; Jurado, N; Núñez-Calvet, M; Artigas, F; Celada, P

    2016-03-01

    The non-competitive NMDA receptor (NMDA-R) antagonist phencyclidine (PCP) markedly disrupts thalamocortical activity, increasing excitatory neuron discharge and reducing low frequency oscillations (LFO, <4Hz) that temporarily group neuronal discharge. These actions are mainly driven by PCP interaction with NMDA-R in GABAergic neurons of the thalamic reticular nucleus and likely underlie PCP psychotomimetic activity. Here we report that classical (haloperidol, chlorpromazine, perphenazine) and atypical (clozapine, olanzapine, quetiapine, risperidone, ziprasidone, aripripazole) antipsychotic drugs--but not the antidepressant citalopram--countered PCP-evoked fall of LFO in the medial prefrontal cortex (mPFC) of anesthetized rats. PCP reduces LFO by breaking the physiological balance between excitatory and inhibitory transmission. Next, we examined the role of different neurotransmitter receptors to reverse PCP actions. D2-R and D1-R blockade may account for classical antipsychotic action since raclopride and SCH-23390 partially reversed PCP effects. Atypical antipsychotic reversal may additionally involve 5-HT1A-R activation (but not 5-HT2A-R blockade) since 8-OH-DPAT and BAYx3702 (but not M100907) fully countered PCP effects. Blockade of histamine H1-R (pyrilamine) and α1-adrenoceptors (prazosin) was without effect. However, the enhancement of GABAA-R-mediated neurotransmission (using muscimol, diazepam or valproate) and the reduction of excitatory neurotransmission (using the mGluR2/3 agonist LY379268 and the preferential kainite/AMPA antagonist CNQX--but not the preferential AMPA/kainate antagonist NBQX) partially or totally countered PCP effects. Overall, these results shed new light on the neurobiological mechanisms used by antipsychotic drugs to reverse NMDA-R antagonist actions and suggest that agents restoring the physiological excitatory/inhibitory balance altered by PCP may be new targets in antipsychotic drug development.

  1. Inhibition by 5-hydroxytryptamine and noradrenaline in substantia gelatinosa of guinea-pig spinal trigeminal nucleus.

    PubMed

    Grudt, T J; Williams, J T; Travagli, R A

    1995-05-15

    1. Whole-cell and intracellular recordings were made from neurons in slices of guinea-pig spinal trigeminal nucleus pars caudalis. 2. 5-Hydroxytryptamine (5-HT) hyperpolarized 70% of neurons by activating 5-HT1A receptors. The effect was mimicked by 5-carboxamidotryptamine (5-CT) and (+/-)-2-dipropylamino-8-hydroxy-1,2,3,4-tetrahydronapthalene hydrobromide (8-OH-DPAT) and antagonized by 1-(2-methoxyphenyl)-4-[4-(2-phthalimido)-butyl]-piperazine hydrobromide (NAN 190) and pindobind-5-HT1A. Nine per cent of the neurons were depolarized by 5-HT. 3. In about 20% of recordings, 5-HT also evoked repetitive inhibitory postsynaptic potentials that were mediated by glycine. 4. Noradrenaline (NA) hyperpolarized 71% of neurons. This effect was mediated by activation of alpha 2-adrenoceptors, since 5-bromo-N-(4,5-dihydro-1H-imidazol-2-yl)-6-quinoxalinamine (UK14304) also caused a hyperpolarization and idazoxan (1 microM) blocked the hyperpolarization to both NA and UK14304. Phenylephrine depolarized a subset of neurons and this depolarization was blocked by prazosin, suggesting an action mediated by activation of alpha 1-adrenoceptors. 5. NA also evoked repetitive GABAA-mediated inhibitory postsynaptic potentials in about 20% of recordings. The increase in synaptic activity was mimicked by phenylephrine and blocked by prazosin. 6. These results indicate that there are at least two mechanisms through which 5-HT and NA inhibit neurons: (i) in many cells both 5-HT and NA mediate a hyperpolarization through an increase of a potassium conductance; (ii) 5-HT and NA also activated GABA- and glycine-containing interneurons to cause IPSPs in separate groups of cells.

  2. Reduction of the number of new cells reaching olfactory bulbs impairs olfactory perception in the adult opossum.

    PubMed

    Grabiec, Marta; Turlejski, Kris; Djavadian, Rouzanna

    2009-01-01

    In adult mammals cells generated in the subventricular zone (SVZ) migrate to olfactory bulbs (OB). Functional significance of this continuous neurogenesis is not clear. We injected opossums (Monodelphis domestica) for seven consecutive days with a 5HT(1A) agonist (8-OH-DPAT or buspirone) or its antagonist WAY100635. One hour after each of these injections bromodeoxyuridine (BrdU) a marker of dividing cells was also injected. Two months later, when newly generated neurons settled in the OB and matured the ability of these opossums to detect hidden food by olfactory cues was tested. Afterwards, numbers of BrdU-labeled cell nuclei in their OB were counted and a phenotype of labeled cells established. In all groups investigated the majority of new cells differentiated into neurons (55-76%) and a lower proportion into astroglia (6-12%). Numbers of BrdU-labeled cells differed depending on the applied treatment: both agonists of the 5HT(1A) receptor increased these numbers, while its antagonist decreased them. The increased number of new OB interneurons did not change the time required for finding all three food items and therefore did not improve the opossums' performance in this test of the olfactory perception. However, opossums that had the reduced number of new generated OB cells searched longer for each food item and in consequence took three times longer to find all three crickets, than did opossums from other groups. In conclusion, lower numbers of new neurons in the opossums OB correlated with their worse behavioral performance in a test based on olfactory perception.

  3. The effects of chronic ethanol self-administration on hippocampal 5-HT1A receptors in monkeys

    PubMed Central

    Burnett, Elizabeth J.; Grant, Kathleen A.; Davenport, April T.; Hemby, Scott E.; Friedman, David P.

    2014-01-01

    BACKGROUND Chronic alcohol consumption reduces brain serotonin and alters the synaptic mechanisms involved in memory formation. Hippocampal 5-HT1A receptors modulate these mechanisms, but the neuroadaptive response of 5HT1A receptors to chronic alcohol self-administration is not well understood. METHODS Hippocampal tissue from monkeys that voluntarily self-administered ethanol for 12 months (n=9) and accompanying controls (n=8) were prepared for in vitro receptor autoradiography and laser capture microdissection. The 5-HT1A receptor antagonist, [3H]MPPF, and the agonist, [3H]8-OH-DPAT, were used to measure total and G-protein coupled 5-HT1A receptors respectively. The expression of the genes encoding the 5-HT1A receptor and its trafficking protein Yif1B was measured in microdissected dentate gyrus (DG) granule cells and CA1 pyramidal neurons. RESULTS An increase in G-protein coupled, but not total, receptors was observed in the posterior pyramidal cell layer of CA1 in ethanol drinkers compared to controls. Chronic ethanol self-administration was also associated with an up-regulation of total and G-protein coupled 5-HT1A receptors in the posterior DG polymorphic layer. Changes in receptor binding were not associated with concomitant changes in 5-HT1A receptor mRNA expression. Chronic ethanol self-administration was associated with a significant increase in Yif1B gene expression in posterior CA1 pyramidal neurons. CONCLUSIONS Chronic, ethanol self-administration up-regulates hippocampal 5-HT1A receptor density in a region-specific manner that does not appear to be due to alterations at the level of transcription but instead may be due to increased receptor trafficking. Further exploration of the mechanisms mediating chronic ethanol-induced 5-HT1A receptor up-regulation and how hippocampal neurotransmission is altered is warranted. PMID:24467872

  4. Serotonergic involvement in the amelioration of behavioral abnormalities in dopamine transporter knockout mice by nicotine.

    PubMed

    Uchiumi, Osamu; Kasahara, Yoshiyuki; Fukui, Asami; Hall, F Scott; Uhl, George R; Sora, Ichiro

    2013-01-01

    Dopamine transporter knockout (DAT KO) mice exhibit elevated extracellular dopamine levels in brain regions that include the striatum and the nucleus accumbens, but not the prefrontal cortex. DAT KO mice model some aspects of psychiatric disorders, including schizophrenia. Smoking is more common in patients with schizophrenia, suggesting that nicotine might ameliorate aspects of the behavioral abnormalities and/or treatment side effects seen in these individuals. We report nicotine-induced normalization of effects on locomotion and prepulse inhibition of acoustic startle (PPI) in DAT KO mice that require intact serotonin 5-HT1A systems. First, we observed that the marked hyperactivity displayed by DAT KO mice was reduced by administration of nicotine. This nicotine effect was blocked by pretreatment with the non-specific nicotinic acetylcholine (nACh) receptor antagonist mecamylamine, or the 5-HT1A antagonist WAY100635. Secondly, we examined the effects of nicotine on PPI in DAT KO mice. Treatment with nicotine significantly ameliorated the PPI deficits observed in DAT KO mice. The ameliorating action of nicotine on PPI deficits in DAT KO mice was blocked by mecamylamine, the α₇ nACh receptor antagonist methyllycaconitine or WAY100635, while the α₄β₂ nACh receptor antagonist dihydro-β-erythroidinehydrobromide (DHβE) produced only a non-significant trend toward attenuation of nicotine effects. Finally, we observed that administration of the 5-HT1A receptor agonist 8-OH-DPAT also ameliorated the deficit in PPI observed in DAT KO mice. This amelioration was antagonized by pretreatment with WAY100635. These data support the idea that nicotine might ameliorate some of the cognitive dysfunctions found in schizophrenia in a 5-HT1A-dependent fashion. This article is part of a Special Issue entitled 'Cognitive Enhancers'.

  5. Effects of GABA(B), 5-HT(1A), and 5-HT(2) receptor stimulation on activation and inhibition of the rat lateral amygdala following medial geniculate nucleus stimulation in vivo.

    PubMed

    Sokal, David M; Giarola, Alessandra S; Large, Charles H

    2005-01-07

    The input from the medial geniculate nucleus of the thalamus (MGN) to the lateral amygdala is known to be important in the regulation of fear and anxiety. Modulation of this pathway may be useful for the treatment of anxiety disorders. We set out to determine whether simple extracellular electrophysiological techniques could be used to study pharmacological modulation of this pathway in vivo. We studied the effects of GABA(B), 5-HT(1), and 5-HT(2) receptor agonists on activity in the lateral amygdala following stimulation of the MGN in isoflurane-anaesthetised rats. Electrical stimulation of the MGN evoked a characteristic biphasic field potential in the lateral amygdala. Baclofen (10 mg kg(-1), iv) inhibited the evoked potential with an effect that was most marked on the positive-going component (80+/-9% inhibition; P<0.05). Baclofen also significantly reduced paired-pulse inhibition of the negative-going component at short interpulse intervals (<200 ms). The 5-HT(1A) receptor ligands, 8-OH-DPAT (60 microg kg(-1), iv) and WAY-100635 (0.5 mg kg(-1), iv) were without effect on evoked responses or paired-pulse relationship. In contrast, the 5-HT(2) receptor agonist, DOI, caused a rapid inhibition of the field potential (to 59.33+/-11.41% of the baseline response; P<0.05). This effect was blocked by ketanserin, either following systemic (0.5 mg kg(-1), iv) or intra-amygdala administration. These results show that GABA(B) and 5-HT(2) receptor agonists can modulate activation of the lateral amygdala following MGN stimulation; furthermore, GABA(B) receptor agonists appear to have a profound effect on local circuit inhibition within the lateral amygdala. The results support the use of in vivo field potential recording within the MGN-lateral amygdala pathway to evaluate this as a possible site of action for novel anxiolytic drugs.

  6. Role of 5-HT6 receptors in memory formation.

    PubMed

    Meneses, A

    2001-09-01

    Mice lacking the 5-HT(6) receptor presented neither gross anatomical or behavioral abnormalities nor obvious changes in microscopic brain morphology, and their performance in rotarod, open field and novel object testing paradigms revealed no differences compared with wild-type animals. Nevertheless, an association between the 5-HT(6) receptor polymorphism C267T and Alzheimer's disease has been reported. Interestingly, the 5-HT(6) antisense oligonucleotide decreased 5-HT(6) gene expression and enhanced spatial learning acquisition in the water maze. Similarly, injection of the 5-HT(6) receptor antagonist Ro-04-6790 improved learning consolidation in an autoshaping task, while mCPP, scopolamine and dizocilpine decreased performance. The effect induced by scopolamine or dizocilpine, but not that induced by mCPP, was completely or partially reversed by Ro-04-6790. Ro-04-6790 did not modify the 8-OH-DPAT facilitatory effects on learning consolidation. Since Ro-04-6790 facilitatory effect was unaffected by 5-HT(1A), 5-HT(2A/2B/2C), 5-HT(3), 5-HT(4) or 5-HT(7) receptor blockade, the facilitatory effect induced by Ro-04-6790 involved specifically 5-HT6 receptors. Similarly, the 5-HT(6) receptor antagonist SB-271046 improved retention in the water maze and produced a significant performance improvement in aged rats in an operant-delayed alternation task. A series of Ro-04-6790 analogues that penetrate the brain and specifically bind to 5-HT(6) receptors reversed scopolamine-induced retention deficit in a passive avoidance learning test. Collectively, these data provide further support to the notion that 5-HT systems, via 5-HT(6) receptors, also play a significant role in memory formation under normal and dysfunctional memory conditions.

  7. 5-HT(1A) receptors and memory.

    PubMed

    Meneses, Alfredo; Perez-Garcia, Georgina

    2007-01-01

    The study of 5-hydroxytryptamine (5-HT) systems has benefited from the identification, classification and cloning of multiple 5-HT receptors (5-HT(1)-5-HT(7)). Increasing evidence suggests that 5-HT pathways, reuptake site/transporter complex and 5-HT receptors represent a strategic distribution for learning and memory. A key question still remaining is whether 5-HT markers (e.g., receptors) are directly or indirectly contributing to the physiological and pharmacological basis of memory and its pathogenesis or, rather, if they represent protective or adaptable mechanisms (at least in initial stages). In the current paper, the major aim is to revise recent advances regarding mammalian 5-HT(1A) receptors in light of their physiological, pathophysiological and therapeutic implications in memory. An attempt is made to identify and discuss sources of discrepancies by employing an analytic approach to examine the nature and degree of difficulty of behavioral tasks used, as well as implicating other factors (for example, brain areas, training time or duration, and drug administration) which might offer new insights into the understanding and interpretation of these data. In this context, 8-OH-DPAT deserves special attention since for many years it has been the more selective 5-HT drug and, hence, more frequently used. As 5-HT(1A) receptors are key components of serotonergic signaling, investigation of their memory mechanisms and action sites and the conditions under which they might operate, could yield valuable insights. Moreover, selective drugs with agonists, neutral antagonists or inverse agonist properties for 5-HT(1A) (and 5-HT(7)) receptors may constitute a new therapeutic opportunity for learning and memory disorders.

  8. Effects of 5-HT drugs in prefrontal cortex during memory formation and the ketamine amnesia-model.

    PubMed

    Liy-Salmeron, Gustavo; Meneses, Alfredo

    2008-01-01

    This article describes a series of experiments investigating the effects of systemic or intraprefrontal administration of serotonergic agents on ketamine induced memory deficits in rats. First, rats were trained on an operant autoshaping task. Immediately after training, rats were injected with different doses of drug or saline. Following drug administration, rats were tested after 1.5 h for short-term memory (STM) and 24 h for long-term memory (LTM) of conditioned response. An increase or decrease in number of conditioned responses was an index of retention. The major results of this work show that ketamine impaired STM and this effect was reversed, by either systemic or intraprefrontal cortex administration of the agonist 5-HT(1A/7) 8-OH-DPAT, the 5-HT receptor antagonists MDL100907 (5-HT(2A)), SB-399885 (5-HT(6)), and SB-269970 (5-HT(7)). The ketamine STM-impairment effect was not altered by the 5-HT(1A) antagonist WAY 100635 or the 5-HT(1B) antagonist SB-224289. Notably, prefrontal cortex inhibition of translation or transcription interrupted STM without affecting LTM suggesting different signaling mechanisms. The interacting effect of NMDA and serotonin agents in memory function is an interesting and important area of study; both receptors are considered to be important targets for the development of antipsychotic medication. Particularly, 5-HT(1A/7), 5-HT(2A) 5-HT(6), and 5-HT(7) receptors present in prefrontal cortex, represent important targets for development of drugs for the treatment of SMT-deficits.

  9. Function and Distribution of 5-HT2 Receptors in the Honeybee (Apis mellifera)

    PubMed Central

    Thamm, Markus; Rolke, Daniel; Jordan, Nadine; Balfanz, Sabine; Schiffer, Christian; Baumann, Arnd; Blenau, Wolfgang

    2013-01-01

    Background Serotonin plays a pivotal role in regulating and modulating physiological and behavioral processes in both vertebrates and invertebrates. In the honeybee (Apis mellifera), serotonin has been implicated in division of labor, visual processing, and learning processes. Here, we present the cloning, heterologous expression, and detailed functional and pharmacological characterization of two honeybee 5-HT2 receptors. Methods Honeybee 5-HT2 receptor cDNAs were amplified from brain cDNA. Recombinant cell lines were established constitutively expressing receptor variants. Pharmacological properties of the receptors were investigated by Ca2+ imaging experiments. Quantitative PCR was applied to explore the expression patterns of receptor mRNAs. Results The honeybee 5-HT2 receptor class consists of two subtypes, Am5-HT2α and Am5-HT2β. Each receptor gene also gives rise to alternatively spliced mRNAs that possibly code for truncated receptors. Only activation of the full-length receptors with serotonin caused an increase in the intracellular Ca2+ concentration. The effect was mimicked by the agonists 5-methoxytryptamine and 8-OH-DPAT at low micromolar concentrations. Receptor activities were blocked by established 5-HT receptor antagonists such as clozapine, methiothepin, or mianserin. High transcript numbers were detected in exocrine glands suggesting that 5-HT2 receptors participate in secretory processes in the honeybee. Conclusions This study marks the first molecular and pharmacological characterization of two 5-HT2 receptor subtypes in the same insect species. The results presented should facilitate further attempts to unravel central and peripheral effects of serotonin mediated by these receptors. PMID:24324783

  10. Effects of direct- and indirect-acting serotonin receptor agonists on the antinociceptive and discriminative stimulus effects of morphine in rhesus monkeys.

    PubMed

    Li, Jun-Xu; Koek, Wouter; Rice, Kenner C; France, Charles P

    2011-04-01

    Serotonergic (5-HT) systems modulate pain, and drugs acting on 5-HT systems are used with opioids to treat pain. This study examined the effects of 5-HT receptor agonists on the antinociceptive and discriminative stimulus effects of morphine in monkeys. Morphine increased tail-withdrawal latency in a dose-related manner; 5-HT receptor agonists alone increased tail-withdrawal latency at 50 °C but not 55 °C water. The antinociceptive effects of morphine occurred with smaller doses when monkeys received an indirect-acting (fenfluramine) or direct acting (8-OH-DPAT, F13714, buspirone, quipazine, DOM, and 2C-T-7) agonist. The role of 5-HT receptor subtypes in these interactions was confirmed with selective 5-HT(1A) (WAY100635) and 5-HT(2A) (MDL100907) receptor antagonists. None of the 5-HT drugs had morphine-like discriminative stimulus effects; however, fenfluramine and 5-HT(2A) receptor agonists attenuated the discriminative stimulus effects of morphine and this attenuation was prevented by MDL100907. The 5-HT(1A) receptor agonists did not alter the discriminative stimulus effects of morphine. Thus, 5-HT receptor agonists increase the potency of morphine in an assay of antinociception, even under conditions where 5-HT agonists are themselves without effect (ie, 55 °C water), without increasing (and in some cases decreasing) the potency of morphine in a drug discrimination assay. Whereas 5-HT(2A) receptor agonists increase the potency of morphine for antinociception at doses that have no effect on the rate of operant responding, 5-HT(1A) receptor agonists increase the potency of morphine only at doses that eliminate operant responding. These data suggest that drugs acting selectively on 5-HT receptor subtypes could help to improve the use of opioids for treating pain.

  11. Characterization of the discriminative stimulus effects of lorcaserin in rats.

    PubMed

    Serafine, Katherine M; Rice, Kenner C; France, Charles P

    2016-09-01

    Lorcaserin is approved by the Food and Drug Administration for treating obesity and is under consideration for treating substance use disorders; it has agonist properties at serotonin (5-HT)2C receptors and might also have agonist properties at other 5-HT receptor subtypes. This study used drug discrimination to investigate the mechanism(s) of action of lorcaserin. Male Sprague-Dawley rats discriminated 0.56 mg/kg i.p. lorcaserin from saline while responding under a fixed-ratio 5 schedule for food. Lorcaserin (0.178-1.0 mg/kg) dose-dependently increased lorcaserin-lever responding. The 5-HT2C receptor agonist mCPP and the 5-HT2A receptor agonist DOM each occasioned greater than 90% lorcaserin-lever responding in seven of eight rats. The 5-HT1A receptor agonist 8-OH-DPAT occasioned greater than 90% lorcaserin-lever responding in four of seven rats. The 5-HT2C receptor selective antagonist SB 242084 attenuated lorcaserin-lever responding in all eight rats and the 5-HT2A receptor selective antagonist MDL 100907 attenuated lorcaserin-lever responding in six of seven rats. These results suggest that, in addition to agonist properties at 5-HT2C receptors, lorcaserin also has agonist properties at 5-HT2A and 5-HT1A receptors. Because some drugs with 5-HT2A receptor agonist properties are abused, it is important to fully characterize the behavioral effects of lorcaserin while considering its potential for treating substance use disorders.

  12. An altered spinal serotonergic system contributes to increased thermal nociception in an animal model of depression.

    PubMed

    Rodríguez-Gaztelumendi, Antonio; Rojo, María Luisa; Pazos, Angel; Díaz, Alvaro

    2014-06-01

    The olfactory bulbectomized (OB) rat, an animal model of chronic depression with comorbid anxiety, exhibits a profound dysregulation of the brain serotonergic signalling, a neurotransmission system involved in pain transmission and modulation. We here report an increased nociceptive response of OB rats in the tail flick test which is reverted after chronic, but not acute, administration of fluoxetine. Autoradiographic studies demonstrated down-regulation of 5-HT transporters ([(3)H]citalopram binding) and decreased functionality of 5-HT1A receptors (8-OH-DPAT-stimulated [(35)S]GTPγS binding) in the dorsal horn of the lumbar spinal cord in OB rats. Acute administration of fluoxetine (5-40 mg/kg i.p.) did not modify tail flick latencies in OB rats. However, chronic fluoxetine (10 mg/kg/day s.c., 14 days; osmotic minipumps) progressively attenuated OB-associated thermal hyperalgesia, and a total normalization of the nociceptive response was achieved at the end of the treatment with the antidepressant. In these animals, autoradiographic studies revealed further down-regulation of 5-HT transporters and normalization in the functionality of 5-HT1A receptors on the spinal cord. On the other hand, acute morphine (0.5-10 mg/kg s.c.) produced a similar analgesic effect in OB and sham and OB rats, and no changes were detected in the density ([(3)H]DAMGO binding) and functionality (DAMGO-stimulated [(35)S]GTPγS binding) of spinal μ-opioid receptors in OB rats before and after chronic fluoxetine. Our findings demonstrate the participation of the spinal serotonergic system in the increased thermal nociception exhibited by the OB rat and the antinociceptive effect of chronic fluoxetine in this animal model of depression.

  13. Reduced vesicular monoamine transport disrupts serotonin signaling but does not cause serotonergic degeneration.

    PubMed

    Alter, Shawn P; Stout, Kristen A; Lohr, Kelly M; Taylor, Tonya N; Shepherd, Kennie R; Wang, Minzheng; Guillot, Thomas S; Miller, Gary W

    2016-01-01

    We previously demonstrated that mice with reduced expression of the vesicular monoamine transporter 2 (VMAT2 LO) undergo age-related degeneration of the catecholamine-producing neurons of the substantia nigra pars compacta and locus ceruleus and exhibit motor disturbances and depressive-like behavior. In this work, we investigated the effects of reduced vesicular transport on the function and viability of serotonin neurons in these mice. Adult (4-6 months of age), VMAT2 LO mice exhibit dramatically reduced (90%) serotonin release capacity, as measured by fast scan cyclic voltammetry. We observed changes in serotonin receptor responsivity in in vivo pharmacological assays. Aged (months) VMAT2 LO mice exhibited abolished 5-HT1A autoreceptor sensitivity, as determined by 8-OH-DPAT (0.1 mg/kg) induction of hypothermia. When challenged with the 5HT2 agonist, 2,5-dimethoxy-4-iodoamphetamine (1 mg/kg), VMAT2 LO mice exhibited a marked increase (50%) in head twitch responses. We observed sparing of serotonergic terminals in aged mice (18-24 months) throughout the forebrain by SERT immunohistochemistry and [(3)H]-paroxetine binding in striatal homogenates of aged VMAT2 LO mice. In contrast to their loss of catecholamine neurons of the substantia nigra and locus ceruleus, aged VMAT2 LO mice do not exhibit a change in the number of serotonergic (TPH2+) neurons within the dorsal raphe, as measured by unbiased stereology at 26-30 months. Collectively, these data indicate that reduced vesicular monoamine transport significantly disrupts serotonergic signaling, but does not drive degeneration of serotonin neurons.

  14. The Role of Prior Stressor Controllability and the Dorsal Raphé Nucleus in Sucrose Preference and Social Exploration

    PubMed Central

    Christianson, John P.; Paul, Evan D.; Irani, Myra; Thompson, Brittany M.; Kubala, Kenneth H.; Yirmiya, Raz; Watkins, Linda R.; Maier, Steven F.

    2008-01-01

    Research investigating how control over stressors affects behavior often utilizes freezing and shuttle escape learning as the behavioral endpoints. These endpoints have been argued to reflect anxious or depressed states, but these descriptions are problematic. The present study sought to determine the impact of stressor controllability and the dorsal raphé nucleus (DRN) on sucrose preference and juvenile social exploration, putative measures of anhedonia and anxiety that are commonly used in studies of stress per se. In Experiment 1 rats were exposed to escapable (ES) or yoked-inescapable (IS) tailshocks. In Experiment 2 ES or IS was given 7 days before all rats received IS. In Experiment 3 the DRN was inactivated during IS by microinjection of 8-OH-DPAT. Sucrose preference and social exploration were tested for several days after stress. A fourth experiment confirmed that juvenile social exploration is sensitive to traditional β-carboline and benzodiazepine manipulations. Both ES and IS reduced sucrose preference, but only IS reduced social exploration. Prior treatment with ES prevented the effect of IS on social exploration but did not prevent the effect of IS on sucrose preference and inactivation of the DRN prevented the effect of IS on social exploration but did not change sucrose preference. The present results indicate that social exploration but not sucrose preference is sensitive to prior stressor controllability, and that DRN activation mediates the effect of IS on social exploration. We argue that DRN-5-HT activation mediates a state of generalized anxiety produced by uncontrollable stress and that juvenile social exploration is a useful behavioral endpoint in stressor controllability studies. PMID:18554730

  15. Cocaine Modulates Mammalian Circadian Clock Timing by Decreasing Serotonin Transport in the SCN

    PubMed Central

    Prosser, Rebecca A.; Stowie, Adam; Amicarelli, Mario; Nackenoff, Alex G.; Blakely, Randy D.; Glass, J. David

    2014-01-01

    Cocaine abuse disrupts reward and homeostatic processes through diverse processes, including those involved in circadian clock regulation. Recently we showed that cocaine administration to mice disrupts nocturnal photic phase resetting of the suprachiasmatic (SCN) circadian clock, whereas administration during the day induces non-photic phase shifts. Importantly, the same effects are seen when cocaine is applied to the SCN in vitro, where it blocks photic-like (glutamate-induced) phase shifts at night and induces phase advances during the day. Furthermore, our previous data suggest that cocaine acts in the SCN by enhancing serotonin (5-HT) signaling. For example, the in vitro actions of cocaine mimic those of 5-HT and are blocked by the 5-HT antagonist, metergoline, but not the dopamine receptor antagonist, fluphenazine. Although our data are consistent with cocaine acting through enhance 5-HT signaling, the nonselective actions of cocaine as an antagonist of monoamine transporters raises the question of whether inhibition of the 5-HT transporter (SERT) is key to its circadian effects. Here we investigate this issue using transgenic mice expressing a SERT that exhibits normal 5-HT recognition and transport but significantly reduced cocaine potency (SERT Met172). Circadian patterns of SCN behavioral and neuronal activity did not differ between WT and SERT Met172 mice, nor did they differ in the ability of the 5-HT1A,2,7 receptor agonist, 8-OH-DPAT to reset SCN clock phase, consistent with the normal SERT expression and activity in the transgenic mice. However, 1) cocaine administration does not induce phase advances when administered in vivo or in vitro in SERT Met172 mice; 2) cocaine does not block photic or glutamate-induced (phase shifts in SERT Met172 mice; and 3) cocaine does not induce long-term changes in free-running period in SERT Met172 mice. We conclude that SERT antagonism is required for the phase shifting of the SCN circadian clock induced by cocaine

  16. Prevention of alcohol-heightened aggression by CRF-R1 antagonists in mice: critical role for DRN-PFC serotonin pathway.

    PubMed

    Quadros, Isabel M; Hwa, Lara S; Shimamoto, Akiko; Carlson, Julia; DeBold, Joseph F; Miczek, Klaus A

    2014-11-01

    Alcohol can escalate aggressive behavior in a significant subgroup of rodents, humans, and nonhuman primates. The present study investigated whether blockade of corticotropin-releasing factor receptor type 1 (CRF-R1) could prevent the emergence of alcohol-heightened aggression in mice. The serotonin (5-HT) pathway from the dorsal raphe nucleus (DRN) to the medial prefrontal cortex (mPFC) by CRF-R1 was investigated as a possible target for the prevention of alcohol-heightened aggressive behavior. Male CFW mice that reliably exhibited aggressive behaviors after consuming 1 g/kg of alcohol received systemic or intra-DRN administration of CRF-R1 antagonists, CP-154,526 or MTIP, before a confrontation with a male conspecific. Blockade of DRN CRF-R1 receptors with both antagonists significantly reduced only alcohol-heightened aggression, whereas systemic administration reduced both alcohol-heightened and species-typical aggression. Next, a 5-HT1A agonist, 8-OH-DPAT, was coadministered with CP-154,526 into the DRN to temporarily disrupt 5-HT activity. This manipulation abolished the antiaggressive effects of intra-DRN CP-154,526. In the mPFC, in vivo microdialysis revealed that extracellular 5-HT levels were increased in mice that consumed alcohol and were then injected with CP-154,526, both systemically or intra-DRN. Neither alcohol nor CP-154,526 alone affected 5-HT release in the mPFC. The present results suggest the DRN as a critical site for CRF-R1 to modulate alcohol-heightened aggression via action on the serotonergic DRN-PFC pathway.

  17. Mice do not habituate to metabolism cage housing--a three week study of male BALB/c mice.

    PubMed

    Kalliokoski, Otto; Jacobsen, Kirsten R; Darusman, Huda S; Henriksen, Trine; Weimann, Allan; Poulsen, Henrik E; Hau, Jann; Abelson, Klas S P

    2013-01-01

    The metabolism cage is a barren, non-enriched, environment, combining a number of recognized environmental stressors. We investigated the ability of male BALB/c mice to acclimatize to this form of housing. For three weeks markers of acute and oxidative stress, as well as clinical signs of abnormality were monitored. Forced swim tests were conducted to determine whether the animals experienced behavioral despair and the serotonergic integrity was tested using an 8-OH-DPAT challenge. The metabolism cage housed mice excreted approximately tenfold higher amounts of corticosterone metabolites in feces throughout the study when compared to controls. Urinary biomarkers confirmed that these mice suffered from elevated levels of oxidative stress, and increased creatinine excretions indicated increased muscle catabolism. Changes in the core body temperature (stress-induced hyperthermia) and the fur state of the mice also indicated impaired well-being in the metabolism cage housed mice. However, monitoring body weight and feed intake was found misleading in assessing the wellbeing of mice over a longer time course, and the forced swim test was found poorly suited for studying chronic stress in mice in the present setup. In conclusion, the mice were found not to acclimatize to the metabolism cages whereby concern for animal welfare would dictate that mice should be housed in this way for as short periods as possible. The elevated degree of HPA axis activity, oxidative stress, and increased overall metabolism warrant caution when interpreting data obtained from metabolism cage housed mice, as their condition cannot be considered representative of a normal physiology.

  18. Effect of the selective noradrenergic reuptake inhibitor reboxetine on the firing activity of noradrenaline and serotonin neurons.

    PubMed

    Szabo, S T; Blier, P

    2001-06-01

    Reboxetine is a non-tricyclic antidepressant with selective noradrenergic (NA) reuptake-blocking effects. The effects of acute and sustained administration of reboxetine, on the firing activity of locus coeruleus NA neurons and dorsal raphe 5-HT neurons, were assessed using in vivo extracellular unitary recording in rats anaesthetized with chloral hydrate. Reboxetine (0.1-1.25 mg/kg, i.v.) dose-dependently decreased the firing activity of NA neurons (ED50 = 480 +/- 14 microg/kg). A 2-day treatment with reboxetine at 1.25, 2.5, 5, or 10 mg/kg per day (using osmotic minipumps implanted subcutaneously) produced significant decreases of 52%, 68%, 81%, and 83%, respectively, of NA firing activity. When the reboxetine treatment (2.5 mg/kg per day) duration was prolonged to 7 days, a 66% decrease in NA firing activity was observed which further decreased to 80% after 21 days of treatment. In contrast, 5-HT neuron firing rate remained unaltered following short- and long-term reboxetine treatments. The suppressant effect of the alpha2-adrenoceptor agonist clonidine on the firing activity of NA neurons was unchanged in long-term reboxetine-treated rats, but its effect on the firing activity of 5-HT neurons was blunted. The enhancement of NA firing activity by the 5-HT1A agonist 8-OH-DPAT was abolished in long-term reboxetine-treated rats, whereas, the inhibitory effect of the 5-HT2 agonist DOI was attenuated by about three-fold. In conclusion, sustained NA reuptake blockade by reboxetine lead to profound alterations in the function of NA neurons and of 5-HT receptors modulating their firing activity.

  19. Serotonergic modulation of LTP at excitatory and inhibitory synapses in the developing rat visual cortex.

    PubMed

    Moreau, A W; Amar, M; Callebert, J; Fossier, P

    2013-05-15

    The stability and efficacy of neuronal circuits are achieved through a detailed balance between pyramidal cell and interneuron activities. Interestingly, the neocortical excitatory-inhibitory (E-I) balance is actively maintained at the soma of Layer 5 pyramidal neurons which receive 20% of excitation and 80% of inhibition after dendritic integration, and this is not affected by changes in synaptic strength. To infer the role of serotonergic neuromodulation on the activity-dependent maintenance of the E-I balance, we performed continuous voltage clamp measurements of stimulation-locked conductance dynamics in Layer 5 pyramidal neurons before and after long-term potentiation (LTP) induction, together with chronic or acute manipulation of serotonin function. When a theta-burst stimulation was applied in Layer 2/3 of 5-HT depleted cortical slices (after in vivo treatment with the tryptophan hydroxylase inhibitor p-chlorophenylalanine (pCPA)), or after in vitro perfusion of the potent 5-HT1A receptor antagonist WAY-100,635, we observed a persistent shift of the ratio between excitation and inhibition toward more inhibition. This was due to a strong LTP of inhibition co-aligned with a weak LTP of excitation, whereas the same protocol caused a similar potentiation of excitatory and inhibitory inputs when applied in control slices. In contrast, neither excitatory nor inhibitory postsynaptic currents were potentiated when LTP protocols were delivered in the presence of either the selective serotonin reuptake inhibitor citalopram or the 5-HT1A receptor agonist 8-OH-DPAT. This is the first demonstration that serotonergic neuromodulation is crucial for the maintenance of the neocortical E-I balance during high-frequency regimes.

  20. Serotonin receptors in suicide victims with major depression.

    PubMed

    Stockmeier, C A; Dilley, G E; Shapiro, L A; Overholser, J C; Thompson, P A; Meltzer, H Y

    1997-02-01

    Serotonin1A (5-HT1A) and serotonin2A (5-HT2A) receptors in the brain have been implicated in the pathophysiology of suicide. Brain samples were collected at autopsy from suicide victims with a current episode of major depression and matched comparison subjects who died of natural or accidental causes. Retrospective psychiatric assessments were collected from knowledgeable informants for all suicide victims and most of the comparison subjects. Psychiatric diagnoses were determined according to DSM-III-R criteria. Any subjects with current psychoactive substance use disorders were excluded. Quantitative receptor autoradiography was used in serial sections of the right prefrontal cortex (area 10) and hippocampus to measure the binding of [3H]8-hydroxy-2-(di-n-propyl)-aminotetralin ([3H]8-OH-DPAT) to 5-HT1A receptors and [3H]ketanserin to 5-HT2A receptors. Analysis of covariance was used to compare control subjects and suicide victims with major depression. The age of subjects, the time from death to freezing the tissue (postmortem interval), and the storage time of tissues in the freezer were used as covariates in the analyses. There were no significant differences between suicide victims with major depression and comparison subjects in 5-HT1A or 5-HT2A receptors in area 10 of the right prefrontal cortex or the hippocampus. The current results suggest that the number of 5-HT1A and 5-HT2A receptors in the right prefrontal cortex (area 10) or hippocampus are not different in suicide victims with major depression.

  1. The Antidepressant-Like Effect of Fish Oil: Possible Role of Ventral Hippocampal 5-HT1A Post-synaptic Receptor.

    PubMed

    Carabelli, Bruno; Delattre, Ana Marcia; Pudell, Claudia; Mori, Marco Aurélio; Suchecki, Deborah; Machado, Ricardo B; Venancio, Daniel Paulino; Piazzetta, Sílvia Regina; Hammerschmidt, Ivilim; Zanata, Sílvio M; Lima, Marcelo M S; Zanoveli, Janaína Menezes; Ferraz, Anete Curte

    2015-08-01

    The pathophysiology of depression is not completely understood; nonetheless, numerous studies point to serotonergic dysfunction as a possible cause. Supplementation with fish oil rich docosahexaenoic (DHA) and eicosapentaenoic acids (EPA) during critical periods of development produces antidepressant effects by increasing serotonergic neurotransmission, particularly in the hippocampus. In a previous study, the involvement of 5-HT1A receptors was demonstrated and we hypothesized that fish oil supplementation (from conception to weaning) alters the function of post-synaptic hippocampal 5-HT1A receptors. To test this hypothesis, female rats were supplemented with fish oil during habituation, mating, gestation, and lactation. The adult male offspring was maintained without supplementation until 3 months of age, when they were subjected to the modified forced swimming test (MFST) after infusion of vehicle or the selective 5-HT1A antagonist, WAY100635, and frequency of swimming, immobility, and climbing was recorded for 5 min. After the behavioral test, the hippocampi were obtained for quantification of serotonin (5-HT) and its metabolite, 5-hydroxyindoleacetic acid (5-HIAA) and for 5-HT1A receptor expression by Western blotting analysis. Fish oil-supplemented offspring displayed less depressive-like behaviors in the MFST reflected by decreased immobility and increased swimming and higher 5-HT hippocampal levels. Although there was no difference in the expression of hippocampal 5-HT1A receptors, intra-hippocampal infusion of a sub-effective dose of 8-OH-DPAT enhanced the antidepressant effect of fish oil in supplemented animals. In summary, the present findings suggest that the antidepressant-like effects of fish oil supplementation are likely related to increased hippocampal serotonergic neurotransmission and sensitization of hippocampal 5-HT1A receptors.

  2. 5-HT(1A)-like receptor activation inhibits abstinence-induced methamphetamine withdrawal in planarians.

    PubMed

    Rawls, Scott M; Shah, Hardik; Ayoub, George; Raffa, Robert B

    2010-10-29

    No pharmacological therapy is approved to treat methamphetamine physical dependence, but it has been hypothesized that serotonin (5-HT)-enhancing drugs might limit the severity of withdrawal symptoms. To test this hypothesis, we used a planarian model of physical dependence that quantifies withdrawal as a reduction in planarian movement. Planarians exposed to methamphetamine (10 μM) for 60 min, and then placed (tested) into drug-free water for 5 min, displayed less movement (i.e., withdrawal) than either methamphetamine-naïve planarians tested in water or methamphetamine-exposed planarians tested in methamphetamine. A concentration-related inhibition of withdrawal was observed when methamphetamine-exposed planarians were placed into a solution containing either methamphetamine and 5-HT (0.1-100 μM) or methamphetamine and the 5-HT(1A) receptor agonist 8-hydroxy-N,N-dipropyl-2-aminotetralin (8-OH-DPAT) (10, 20 μM). Planarians with prior methamphetamine exposure displayed enhanced withdrawal when tested in a solution of the 5-HT(1A) receptor antagonist N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridyl)cyclohexanecarboxamide (WAY 100635) (1 μM). Methamphetamine-induced withdrawal was not affected by the 5-HT(2B/2C) receptor agonist meta-chlorophenylpiperazine (m-CPZ) (0.1-20 μM). These results provide pharmacological evidence that serotonin-enhancing drugs inhibit expression of methamphetamine physical dependence in an invertebrate model of withdrawal, possibly through a 5-HT(1A)-like receptor-dependent mechanism.

  3. Serotonergic activation of 5HT1A and 5HT2 receptors modulates sexually dimorphic communication signals in the weakly electric fish Apteronotus leptorhynchus.

    PubMed

    Smith, G Troy; Combs, Nicole

    2008-06-01

    Serotonin modulates agonistic and reproductive behavior across vertebrate species. 5HT(1A) and 5HT(1B) receptors mediate many serotonergic effects on social behavior, but other receptors, including 5HT(2) receptors, may also contribute. We investigated serotonergic regulation of electrocommunication signals in the weakly electric fish Apteronotus leptorhynchus. During social interactions, these fish modulate their electric organ discharges (EODs) to produce signals known as chirps. Males chirp more than females and produce two chirp types. Males produce high-frequency chirps as courtship signals; whereas both sexes produce low-frequency chirps during same-sex interactions. Serotonergic innervation of the prepacemaker nucleus, which controls chirping, is more robust in females than males. Serotonin inhibits chirping and may contribute to sexual dimorphism and individual variation in chirping. We elicited chirps with EOD playbacks and pharmacologically manipulated serotonin receptors to determine which receptors regulated chirping. We also asked whether serotonin receptor activation generally modulated chirping or more specifically targeted particular chirp types. Agonists and antagonists of 5HT(1B/1D) receptors (CP-94253 and GR-125743) did not affect chirping. The 5HT(1A) receptor agonist 8OH-DPAT specifically increased production of high-frequency chirps. The 5HT(2) receptor agonist DOI decreased chirping. Receptor antagonists (WAY-100635 and MDL-11939) opposed the effects of their corresponding agonists. These results suggest that serotonergic inhibition of chirping may be mediated by 5HT(2) receptors, but that serotonergic activation of 5HT(1A) receptors specifically increases the production of high-frequency chirps. The enhancement of chirping by 5HT(1A) receptors may result from interactions with cortisol and/or arginine vasotocin, which similarly enhance chirping and are influenced by 5HT(1A) activity in other systems.

  4. Effects of the 5-HT receptor antagonists GR127935 (5-HT1B/1D) and MDL100907 (5-HT2A) in the consolidation of learning.

    PubMed

    Meneses, A; Terrón, J A; Hong, E

    1997-12-01

    We have previously reported that 5-HT1B/1D and 5-HT2A/2B/2C receptors play a role in learning and memory. The present investigation was devoted to analyze further in the autoshaping learning task: (1) the effects of the 5-HT1A/1B/1D receptor agonist, GR46611, the 5-HT1B/1D receptor antagonist, GR127935, and the selective 5-HT2A receptor antagonist, MDL100907. Consistent with a role of 5-HT1B/1D receptors in learning, the post-training injection of GR46611 (1-10 mg/kg) decreased the consolidation of learning whereas GR127935 (10 mg/kg) increased it; the effects of both drugs were reversed by PCA pretreatment. GR127935 abolished the decrease induced by GR46611, TFMPP and mCPP, whereas MDL100907 (0.1-3.0 mg/kg) had no effect by itself but abolished the effects of DOI, ketanserin and TFMPP and moderately inhibited the effects elicited by mCPP, 1-NP and mesulergine. Neither did GR127935 nor MDL100907 significantly modify the increase in the consolidation of learning induced by 8-OH-DPAT. Thus, the present findings suggest that stimulation of presynaptic 5-HT1B/1D receptors impairs the consolidation of learning whilst stimulation of 5-HT2A/2C receptors enhances it; the blockade of 5-HT2A receptors has no effects. In addition, 5-HT2 receptors seem to modulate this cognitive stage.

  5. Autoradiographic distribution of 5-HT7 receptors in the human brain using [3H]mesulergine: comparison to other mammalian species

    PubMed Central

    Martín-Cora, Francisco J; Pazos, Angel

    2003-01-01

    The main aim of this investigation was to delineate the distribution of the 5-HT7 receptor in human brain. Autoradiographic studies in guinea-pig and rat brain were also carried out in order to revisit and compare the anatomical distribution of 5-HT7 receptors in different mammalian species.Binding studies were performed in rat frontal cortex membranes using 10 nM [3H]mesulergine in the presence of raclopride (10 μM) and DOI (0.8 μM). Under these conditions, a binding site with pharmacological characteristics consistent with those of the 5-HT7 receptors was identified (rank order of binding affinity values: 5-CT>5-HT>5-MeOT>mesulergine ≈methiothepin>8-OH-DPAT=spiperone ≈(+)-butaclamol≫imipramine ≈(±)-pindolol≫ondansetron ≈clonidine ≈prazosin).The autoradiographic studies revealed that the anatomical distribution of 5-HT7 receptors throughout the human brain was heterogenous. High densities were found over the caudate and putamen nuclei, the pyramidal layer of the CA2 field of the hippocampus, the centromedial thalamic nucleus, and the dorsal raphe nucleus. The inner layer of the frontal cortex, the dentate gyrus of the hippocampus, the subthalamic nucleus and superior colliculus, among others, presented intermediate concentrations of 5-HT7 receptors. A similar brain anatomical distribution of 5-HT7 receptors was observed in all three mammalian species studied.By using [3H]mesulergine, we have mapped for the first time the anatomical distribution of 5-HT7 receptors in the human brain, overcoming the limitations previously found in radiometric studies with other radioligands, and also revisiting the distribution in guinea-pig and rat brain. PMID:14656806

  6. Differential serotonergic modulation of two types of aggression in weakly electric fish

    PubMed Central

    Zubizarreta, Lucía; Perrone, Rossana; Stoddard, Philip K.; Costa, Gustavo; Silva, Ana C.

    2012-01-01

    Agonistic aggression has provided an excellent framework to study how conserved circuits and neurochemical mediators control species-specific and context-dependent behavior. The principal inhibitory control upon aggression is serotonin (5-HT) dependent, and the activation of 5-HT1A receptors is involved in its action. To address whether the serotonergic system differentially regulates different types of aggression, we used two species of weakly electric fish: the solitary Gymnotus omarorum and the gregarious Brachyhypopomus gauderio, which display distinctive types of aggression as part of each species' natural behavioral repertoire. We found that in the reproduction-related aggression displayed by B. gauderio after conflict resolution, the serotonergic activity follows the classic pattern in which subordinates exhibit higher 5-HT levels than controls. After the territorial aggression displayed by G. omarorum, however, both dominants and subordinates show lower 5-HT levels than controls, indicating a different response of the serotonergic system. Further, we found interspecific differences in basal serotonin turnover and in the dynamic profile of the changes in 5-HT levels from pre-contest to post-contest. Finally, we found the expected reduction of aggression and outcome shift in the territorial aggression of G. omarorum after 8-OH-DPAT (5-HT1A receptor agonist) administration, but no effect in the reproduction-related aggression of B. gauderio. Our results demonstrate the differential participation of the serotonergic system in the modulation of two types of aggression that we speculate may be a general strategy of the neuroendocrine control of aggression across vertebrates. PMID:23181014

  7. Antinociceptive activity of Tilia americana var. mexicana inflorescences and quercetin in the formalin test and in an arthritic pain model in rats.

    PubMed

    Martínez, Ana Laura; González-Trujano, Ma Eva; Aguirre-Hernández, Eva; Moreno, Julia; Soto-Hernández, Marco; López-Muñoz, Francisco J

    2009-02-01

    Tilia species are well known around the world for their properties in traditional medicine. Antinociceptive activity of hexane, methanol and aqueous extracts from Tilia americana var. mexicana inflorescences was evaluated in the pain-induced functional impairment model in rats (PIFIR). A preliminar 300 mg/kg dosage of aqueous extracts i.p., but not the same dose of methanol or hexane extract, produced an antinociceptive response in rats similar to that of tramadol (17.8 mg/kg i.p.). A dose-response curve from aqueous extract allowed the determination of ED(50) = 364.97 mg/kg in comparison to ED(50) = 10.35 mg/kg for tramadol in this model. A previous HPLC-DAD analysis corroborated by an HPLC-MS technique in this study demonstrated the flavonoid composition in this Tilia aqueous extract revealing the presence of glycosides mainly derived from quercetin. Thus, Tilia aqueous extract and quercetin were tested at 30 and/or 100 mg/kg dosages i.p. in the PIFIR and formalin models producing a significant and dose-dependent antinociceptive response resembling that produced by a total and a partial agonist of 5-HT(1A) receptors like 8-OH-DPAT (0.1 mg/kg, s.c.) and buspirone (5 mg/kg, i.p.), respectively. In all the treatments, antinociceptive response was inhibited in the presence of WAY 100635 (0.12 mg/kg, i.p.). Our results support the analgesic activity of T. americana var. mexicana inflorescences attributed by folk medicine; they also indicate that quercetin is partly responsible for this pharmacological activity that is likely mediated by serotonin 5-HT(1A) receptors.

  8. Hydrocracking phenanthrene and 1-methyl naphthalene: Development of linear free energy relationships

    SciTech Connect

    Landau, R.N.; Korre, S.C.; Neurock, M.; Klein, M.T.; Quann, R.J.

    1994-12-31

    The catalytic hydrocracking reaction pathways, kinetics and mechanisms of 1-methyl naphthalene and phenanthrene were investigated in experiments at 350 C and 68.1 atm H{sub 2} partial pressure (190.6 atm total pressure), using a presulfided Ni/W on USY zeolite catalyst. 1-methyl naphthalene hydrocracking led to 2-methyl naphthalene, methyl tetralins, methyl decalins, pentyl benzene and tetralin. Phenanthrene hydrocracking led to dihydro, tetrahydro and octahydro phenanthrene, butyl naphthalene, tetralin to butyl tetralin and dibutyl benzene. The rate constants for the dealkylation of butyl tetralins produced in the phenanthrene hydrocracking network conform to a linear free energy relationship (LFER), with the heat of formation of the leaving alkyl carbenium ion as the reactivity index.

  9. Pharmacological evidence that 5-HT1D activation induces renal vasodilation by NO pathway in rats.

    PubMed

    García-Pedraza, José-Ángel; García, Mónica; Martín, María-Luisa; Morán, Asunción

    2015-06-01

    5-HT is a powerful vasoconstrictor substance in renal vasculature (mainly by 5-HT₂ activation). Nevertheless, 5-HT is notable for its dual cardiovascular effects, producing both vasodilator and vasoconstrictor actions. This study aimed to investigate whether, behind the predominant serotonergic vasoconstrictor action, THE 5-HT system may exert renal vasodilator actions, and, if so, characterize the 5-HT receptors and possible indirect pathways. Renal perfusion pressure (PP), systemic blood pressure (SBP) and heart rate (HR) measurement in in situ autoperfused rat kidney was determined in phenylephrine infused rats. Intra arterial (i.a.) bolus administration of 5-HT (0.00000125-0.1 μg/kg) decreased renal PP in the presence of a phenylephrine continuous infusion (phenylephrine-infusion group), without modifying SBP or HR. These vasodilator responses were potentiated by 5-HT₂ antagonism (ritanserin, 1 mg/kg i.v.), whereas the responses were abolished by 5-HT₁ /₇ antagonist (methiothepin, 100 μg/kg i.v.) or 5-HT1D antagonist (LY310762, 1 mg/kg i.v.). The i.a. administration (0.00000125 to 0.1 μg/kg) of 5-CT or L-694,247 (5-HT1D agonist) mimicked 5-HT vasodilator effect, while other agonists (1-PBG, α-methyl-5-HT, AS-19 (5-HT₇), 8-OH-DPAT (5-HT1A) or CGS-12066B (5-HT1B)) did not alter baseline haemodynamic variables. L-694,247 vasodilation was abolished by i.v. bolus of antagonists LY310762 (5-HT1D, 1 mg/kg) or L-NAME (nitric oxide, 10 mg/kg), but not by i.v. bolus of indomethacin (cyclooxygenase, 2 mg/kg) or glibenclamide (ATP-dependent K(+) channel, 20 mg/kg). These outcomes suggest that 5-HT1D activation produces a vasodilator effect in the in situ autoperfused kidney of phenylephrine-infusion rats mediated by the NO pathway.

  10. Serotonin 1A, 1B, and 7 receptors of the rat medial nucleus accumbens differentially regulate feeding, water intake, and locomotor activity.

    PubMed

    Clissold, Kara A; Choi, Eugene; Pratt, Wayne E

    2013-11-01

    Serotonin (5-HT) signaling has been widely implicated in the regulation of feeding behaviors in both humans and animal models. Recently, we reported that co-stimulation of 5-HT1&7 receptors of the anterior medial nucleus accumbens with the drug 5-CT caused a dose-dependent decrease in food intake, water intake, and locomotion in rats (Pratt et al., 2009). The current experiments sought to determine which of three serotonin receptor subtypes (5-HT1A, 5-HT1B, or 5-HT7) might be responsible for these consummatory and locomotor effects. Food-deprived rats were given 2-h access to rat chow after stimulation of nucleus accumbens 5-HT1A, 5-HT1B, or 5-HT7 receptors, or blockade of the 5-HT1A or 5-HT1B receptors. Stimulation of 5-HT1A receptors with 8-OH-DPAT (at 0.0, 2.0, 4.0, and 8.0 μg/0.5 μl/side) caused a dose-dependent decrease in food and water intake, and reduced rearing behavior but not ambulation. In contrast, rats that received the 5-HT1B agonist CP 93129 (at 0.0, 1.0, 2.0 and 4.0 μg/0.5 μl/side) showed a significant dose-dependent decrease in water intake only; stimulation of 5-HT7 receptors (AS 19; at 0.0, 1.0, and 5.0 μg/0.5 μl/side) decreased ambulatory activity but did not affect food or water consumption. Blockade of 5-HT1A or 5-HT1B receptors had no lasting effects on measures of food consumption. These data suggest that the food intake, water intake, and locomotor effects seen after medial nucleus accumbens injections of 5-CT are due to actions on separate serotonin receptor subtypes, and contribute to growing evidence for selective roles of individual serotonin receptors within the nucleus accumbens on motivated behavior.

  11. 5-HT1A/1B Receptors as Targets for Optimizing Pigmentary Responses in C57BL/6 Mouse Skin to Stress

    PubMed Central

    Wu, Hua-Li; Pang, Si-Lin; Liu, Qiong-Zhen; Wang, Qian; Cai, Min-Xuan; Shang, Jing

    2014-01-01

    Stress has been reported to induce alterations of skin pigmentary response. Acute stress is associated with increased turnover of serotonin (5-hydroxytryptamine; 5-HT) whereas chronic stress causes a decrease. 5-HT receptors have been detected in pigment cells, indicating their role in skin pigmentation. To ascertain the precise role of 5-HT in stress-induced pigmentary responses, C57BL/6 mice were subjected to chronic restraint stress and chronic unpredictable mild stress (CRS and CUMS, two models of chronic stress) for 21 days, finally resulting in abnormal pigmentary responses. Subsequently, stressed mice were characterized by the absence of a black pigment in dorsal coat. The down-regulation of tyrosinase (TYR) and tyrosinase-related proteins (TRP1 and TRP2) expression in stressed skin was accompanied by reduced levels of 5-HT and decreased expression of 5-HT receptor (5-HTR) system. In both murine B16F10 melanoma cells and normal human melanocytes (NHMCs), 5-HT had a stimulatory effect on melanin production, dendricity and migration. When treated with 5-HT in cultured hair follicles (HFs), the increased expression of melanogenesis-related genes and the activation of 5-HT1A, 1B and 7 receptors also occurred. The serum obtained from stressed mice showed significantly decreased tyrosinase activity in NHMCs compared to that from nonstressed mice. The decrease in tyrosinase activity was further augmented in the presence of 5-HTR1A, 1B and 7 antagonists, WAY100635, SB216641 and SB269970. In vivo, stressed mice received 5-HT precursor 5-hydroxy-l-tryptophan (5-HTP), a member of the class of selective serotonin reuptake inhibitors (fluoxetine; FX) and 5-HTR1A/1B agonists (8-OH-DPAT/CP94253), finally contributing to the normalization of pigmentary responses. Taken together, these data strongly suggest that the serotoninergic system plays an important role in the regulation of stress-induced depigmentation, which can be mediated by 5-HT1A/1B receptors. 5-HT and 5-HTR1A

  12. Effects of novel antipsychotics with mixed D(2) antagonist/5-HT(1A) agonist properties on PCP-induced social interaction deficits in the rat.

    PubMed

    Bruins Slot, Liesbeth A; Kleven, Mark S; Newman-Tancredi, Adrian

    2005-12-01

    Considerable interest has arisen in identifying antipsychotic agents with improved efficacy against negative symptoms, such as social withdrawal. In rats, a social interaction deficit can be induced by the NMDA antagonist phencyclidine (PCP). Here, we examined the effects of antipsychotics, reported to exert dual 5-HT(1A)/D(2) actions, on PCP-induced social interaction deficits. Drugs were administered daily for 3 days in combination with either vehicle or PCP (2.5mg/kg, SC) and social interaction was measured on the last day of drug treatment. Pairs of unfamiliar rats receiving the same treatment were placed in a large open field for 10 min and the number of social behaviors were scored. The results indicate that: (1) PCP significantly reduced social interaction by over 50% compared with vehicle-treated controls; (2) haloperidol (0.0025-0.16 mg/kg, SC) and clozapine (0.04-10mg/kg, IP) did not reverse PCP-induced social interaction deficits; (3) the substituted benzamide remoxipride reversed PCP-induced deficits at 0.63 and 2.5mg/kg (4) the 5-HT(1A) agonist 8-OH-DPAT was inactive (at 0.01-0.63 mg/kg, SC); (5) among compounds reported to exert dual 5-HT(1A)/D(2) actions, SSR181507 (at 0.16 mg/kg, SC) and aripiprazole (at 0.04 and 0.16 mg/kg, IP), but not ziprasidone (0.04-2.5mg/kg, IP), SLV313 (0.0025-0.16 mg/kg, SC) or bifeprunox (0.01-0.63 mg/kg, IP), significantly reversed PCP-induced social interaction deficits; and (6) the 5-HT(1A) receptor antagonist WAY100635 blocked the effects of SSR181507 and aripiprazole. These findings indicate that the balance of activity at 5-HT(1A) and D(2) receptors profoundly influences the activity of antipsychotics in this model of social withdrawal, and their potential benefit on at least some of the negative symptoms of schizophrenia.

  13. Memory time-course: mRNA 5-HT1A and 5-HT7 receptors.

    PubMed

    Perez-Garcia, Georgina; Meneses, Alfredo

    2009-08-24

    In an attempt to clarify conflicting results about serotonin (5-hydroxytryptamine, 5-HT) 5-HT(1A) and 5-HT(7) receptors in memory formation, their mRNA expression was determined by RT-PCR in key brain areas for explicit and implicit memory. The time-course (0-120 h) of autoshaped responses was progressive and mRNA 5-HT(1A) or 5-HT(7) receptors expression monotonically augmented or declined in prefrontal cortex, hippocampus and raphe nuclei, respectively. At 24-48 h acutely 8-OH-DPAT (0.062 mg/kg) administration enhanced memory and attenuated mRNA 5-HT(1A)<5-HT(7) receptors expression respect to saline group. WAY100635 (0.3 mg/kg) or SB-269970 (10.0 mg/kg) did not affect the former, partially blocked or reversed the latter, respectively. Furthermore, lower WAY100635 (0.001-0.1 mg/kg) or SB-269970 (1.0-5.0 mg/kg) doses plus 8-OHDPAT not affected memory; however both combinations suppressed or up-regulated mRNA expression 5-HT(1A) or 5-HT(7) receptors. In contrast, AS19 (5.0 mg/kg) facilitated memory consolidation, decreased or increased hippocampal 5-HT(7) and 5-HT(1A) receptors expression. Together these data revealed that, when both 5-HT(1A) and 5-HT(7) receptors were stimulated by 8-OHDPAT under memory consolidation, subtle changes emerged, not evident at behavioral level though detectable at genes expression. Notably, high levels of efficient memory were maintained even when serotonergic tone, via either 5-HT(1A) or 5-HT(7) receptor, was down- or up-regulated. Nevertheless, WAY100635 plus SB-269970 impaired memory consolidation and suppressed their expression. Considering that serotonergic changes are prominent in AD patients with an earlier onset of disease the present approach might be useful in the identification of functional changes associated to memory formation, memory deficits and reversing or even preventing these deficits.

  14. Selective siRNA-mediated suppression of 5-HT1A autoreceptors evokes strong anti-depressant-like effects.

    PubMed

    Bortolozzi, A; Castañé, A; Semakova, J; Santana, N; Alvarado, G; Cortés, R; Ferrés-Coy, A; Fernández, G; Carmona, M C; Toth, M; Perales, J C; Montefeltro, A; Artigas, F

    2012-06-01

    Depression is a major health problem worldwide. Most prescribed anti-depressants, the selective serotonin reuptake inhibitors (SSRI) show limited efficacy and delayed onset of action, partly due to the activation of somatodendritic 5-HT(1A)-autoreceptors by the excess extracellular serotonin (5-HT) produced by SSRI in the raphe nuclei. Likewise, 5-HT(1A) receptor (5-HT(1A)R) gene polymorphisms leading to high 5-HT(1A)-autoreceptor expression increase depression susceptibility and decrease treatment response. In this study, we report on a new treatment strategy based on the administration of small-interfering RNA (siRNA) to acutely suppress 5-HT(1A)-autoreceptor-mediated negative feedback mechanisms. We developed a conjugated siRNA (C-1A-siRNA) by covalently binding siRNA targeting 5-HT(1A) receptor mRNA with the SSRI sertraline in order to concentrate it in serotonin axons, rich in serotonin transporter (SERT) sites. The intracerebroventricular (i.c.v.) infusion of C-1A-siRNA to mice resulted in its selective accumulation in serotonin neurons. This evoked marked anti-depressant-like effects in the forced swim and tail suspension tests, but did not affect anxiety-like behaviors in the elevated plus-maze. In parallel, C-1A-siRNA administration markedly decreased 5-HT(1A)-autoreceptor expression and suppressed 8-OH-DPAT-induced hypothermia (a pre-synaptic 5-HT(1A)R effect in mice) without affecting post-synaptic 5-HT(1A)R expression in hippocampus and prefrontal cortex. Moreover, i.c.v. C-1A-siRNA infusion augmented the increase in extracellular serotonin evoked by fluoxetine in prefrontal cortex to the level seen in 5-HT(1A)R knockout mice. Interestingly, intranasal C-1A-siRNA administration produced the same effects, thus opening the way to the therapeutic use of C-1A-siRNA. Hence, C-1A-siRNA represents a new approach to treat mood disorders as monotherapy or in combination with SSRI.

  15. The differential effects of 5-HT(1A) receptor stimulation on dopamine receptor-mediated abnormal involuntary movements and rotations in the primed hemiparkinsonian rat.

    PubMed

    Dupre, Kristin B; Eskow, Karen L; Negron, Giselle; Bishop, Christopher

    2007-07-16

    Serotonin 1A receptor (5-HT(1A)R) agonists have emerged as valuable supplements to l-DOPA therapy, demonstrating that they can decrease side effects and enhance motor function in animal models of Parkinson's disease (PD) and human PD patients. The precise mechanism by which these receptors act remains unknown and there is limited information on how 5-HT(1A)R stimulation impacts striatal dopamine (DA) D1 receptor (D1R) and D2 receptor (D2R) function. The current study examined the effects of 5-HT(1A)R stimulation on DA receptor-mediated behaviors. Male Sprague-Dawley rats were rendered hemiparkinsonian by unilateral 6-OHDA lesions and primed with the D1R agonist SKF81297 (0.8 mg/kg, i.p.) in order to sensitize DA receptors. Using a randomized within subjects design, rats received a first injection of: Vehicle (dH(2)O) or the 5-HT(1A)R agonist +/-8-OH-DPAT (0.1 or 1.0 mg/kg, i.p.), followed by a second injection of: Vehicle (dimethyl sulfoxide), the D1R agonist SKF81297 (0.8 mg/kg, i.p.), the D2R agonist quinpirole (0.2 mg/kg, i.p.), or l-DOPA (12 mg/kg+benserazide, 15 mg/kg, i.p.). On test days, rats were monitored over a 2-h period immediately following the second injection for abnormal involuntary movements (AIMs), analogous to dyskinesia observed in PD patients, and contralateral rotations. The present findings indicate that 5-HT(1A)R stimulation reduces AIMs induced by D1R, D2R and l-DOPA administration while its effects on DA agonist-induced rotations were receptor-dependent, suggesting that direct 5-HT(1A)R and DA receptor interactions may contribute to the unique profile of 5-HT(1A)R agonists for the improvement of PD treatment.

  16. The involvement of 5-HT-like receptors in the regulation of food intake in rainbow trout (Oncorhynchus mykiss).

    PubMed

    Pérez Maceira, Jorge J; Mancebo, María J; Aldegunde, Manuel

    2014-04-01

    It is known that in fish the serotonergic system is part of the neural network that controls feeding and that a pharmacologically induced increase in the brain 5-HT inhibits food intake. However, nothing is known about the 5-HT receptors involved in this inhibitory effect. In this study, we investigated the effects of several 5-HT1 and 5-HT2 receptor agonists on food intake in rainbow trout. In the first experiment, fish were injected i.p. or i.c.v. with two 5-HT1B receptor agonists, anpirtoline (2mg/kg, i.p.) and CP93129 (100 and 200μg/kg, i.c.v.). Neither of these treatments significantly altered food intake. In a second set of experiments, different groups of fish were injected i.p. (1mg/kg) or i.c.v. (30μg/kg) with the 5-HT1A receptor agonist 8-OH-DPAT. In both cases, administration of the 5-HT1A receptor agonist inhibited food intake. In a third set of experiments, we explored the effects of different 5-HT2 receptor agonists. Different groups of fish were injected i.p. or i.c.v. with the mixed 5-HT2B/2C agonist m-CPP (5mg/kg, i.p.), 5-HT2C agonist MK212 (60μg/kg, i.c.v.) and 5-HT2B agonist BW723C86 (50 and 100μg/kg, i.c.v.). Administration of the 5-HT2B/2C and 5HT2C receptor agonists significantly inhibited food intake. Administration of the lowest dose of the 5-HT2B receptor agonist did not have any significant effect, while administration of the highest dose induced a significant increase in food intake. Activation of the 5-HT1A-like (food intake inhibition) and 5-HT1B-like (no effect on food intake) receptors in the rainbow trout induced different effects on food intake from those observed in mammals. We conclude that in rainbow trout the anorexigenic actions of 5-HT are probably mediated by activation of 5-HT1A and 5-H2C-like receptors.

  17. Long-Lasting Effects of Sepsis on Circadian Rhythms in the Mouse

    PubMed Central

    O'Callaghan, Emma K.; Anderson, Sean T.; Moynagh, Paul N.; Coogan, Andrew N.

    2012-01-01

    Daily patterns of activity and physiology are termed circadian rhythms and are driven primarily by an endogenous biological timekeeping system, with the master clock located in the suprachiasmatic nucleus. Previous studies have indicated reciprocal relationships between the circadian and the immune systems, although to date there have been only limited explorations of the long-term modulation of the circadian system by immune challenge, and it is to this question that we addressed ourselves in the current study. Sepsis was induced by peripheral treatment with lipopolysaccharide (5 mg/kg) and circadian rhythms were monitored following recovery. The basic parameters of circadian rhythmicity (free-running period and rhythm amplitude, entrainment to a light/dark cycle) were unaltered in post-septic animals compared to controls. Animals previously treated with LPS showed accelerated re-entrainment to a 6 hour advance of the light/dark cycle, and showed larger phase advances induced by photic stimulation in the late night phase. Photic induction of the immediate early genes c-FOS, EGR-1 and ARC was not altered, and neither was phase-shifting in response to treatment with the 5-HT-1a/7 agonist 8-OH-DPAT. Circadian expression of the clock gene product PER2 was altered in the suprachiasmatic nucleus of post-septic animals, and PER1 and PER2 expression patterns were altered also in the hippocampus. Examination of the suprachiasmatic nucleus 3 months after treatment with LPS showed persistent upregulation of the microglial markers CD-11b and F4/80, but no changes in the expression of various neuropeptides, cytokines, and intracellular signallers. The effects of sepsis on circadian rhythms does not seem to be driven by cell death, as 24 hours after LPS treatment there was no evidence for apoptosis in the suprachiasmatic nucleus as judged by TUNEL and cleaved-caspase 3 staining. Overall these data provide novel insight into how septic shock exerts chronic effects on the

  18. ACUTE ETHANOL DISRUPTS PHOTIC AND SEROTONERGIC CIRCADIAN CLOCK PHASE-RESETTING IN THE MOUSE

    PubMed Central

    Brager, Allison J.; Ruby, Christina L.; Prosser, Rebecca A.; Glass, J. David

    2011-01-01

    Background Alcohol abuse is associated with impaired circadian rhythms and sleep. Ethanol administration disrupts circadian clock phase-resetting, suggesting a mode for the disruptive effect of alcohol abuse on the circadian timing system. In this study, we extend previous work in C57BL/6J mice to: 1) characterize the SCN pharmacokinetics of acute systemic ethanol administration; 2) explore the effects of acute ethanol on photic and non-photic phase-resetting; and 2) determine if the SCN is a direct target for photic effects. Methods First, microdialysis was used to characterize the pharmacokinetics of acute i.p. injections of 3 doses of ethanol (0.5, 1.0 and 2.0 g/kg) in the mouse suprachiasmatic (SCN) circadian clock. Second, the effects of acute i.p. ethanol administration on photic phase-delays and serotonergic ([+]8-OH-DPAT-induced) phase-advances of the circadian activity rhythm were assessed. Third, the effects of reverse-microdialysis ethanol perfusion of the SCN on photic phase-resetting were characterized. Results Peak ethanol levels from the 3 doses of ethanol in the SCN occurred within 20–40 min post-injection with half-lives for clearance ranging from 0.6–1.8 hr. Systemic ethanol treatment dose-dependently attenuated photic and serotonergic phase-resetting. This treatment also did not affect basal SCN neuronal activity as assessed by Fos expression. Intra-SCN perfusion with ethanol markedly reduced photic phase-delays. Conclusions These results confirm that acute ethanol attenuates photic phase-delay shifts and serotonergic phase-advance shifts in the mouse. This dual effect could disrupt photic and non-photic entrainment mechanisms governing circadian clock timing. It is also significant that the SCN clock is a direct target for disruptive effects of ethanol on photic shifting. Such actions by ethanol could underlie the disruptive effects of alcohol abuse on behavioral, physiological, and endocrine rhythms associated with alcoholism. PMID:21463340

  19. 5-HT is a potent relaxant in rat superior mesenteric veins.

    PubMed

    Watts, Stephanie W; Darios, Emma S; Seitz, Bridget M; Thompson, Janice M

    2015-02-01

    Serotonin (5-HT, 5-hydroxytryptamine) reduces blood pressure of the conscious rat when administered chronically (1 week). 5-HT does not directly relax isolated arteries, and microsphere experiments in 5-HT-infused rats suggested that 5-HT increased flow to the splanchnic bed. We hypothesized that 5-HT increased splanchnic flow because of direct venous relaxation; our focus was thus on the superior mesenteric vein (SMV) as an important vein in splanchnic circulation. Real-time RT-PCR, immunohistochemistry and Western analyses supported the predominant expression of the 5-HT2B and 5-HT7 receptor in the SMV. The SMV was mounted in tissue baths for measurement of isometric contraction. 5-HT caused a concentration-dependent relaxation of the endothelin-1 (ET-1)-contracted vein. The threshold of 5-HT-induced venous relaxation was significantly lower than for 5-HT-induced venous contraction (∼2 vs. 700 nmol/L, respectively). A series of serotonergic agonists established in their use of receptor characterization was tested, and the following rank order of potency found for agonist-induced relaxation (receptor selectivity): 5-CT (5-HT1/5-HT7)>5-HT = LP-44 (5-HT7)>PNU109291 (5-HT1D) = BW723C86 (5-HT2B). 8-OH-DPAT (5-HT1A/7), CP93129 (5-HT1B), mCPBG (5-HT3/4), AS19 (5-HT7) and TCB-2 (5-HT2A) did not relax the isolated vein. Consistent with these findings, two different 5-HT7 receptor antagonists SB 269970 and LY215840 but not the 5-HT2B receptor antagonist LY272015 nor the nitric oxide synthase inhibitor LNNA abolished 5-CT-induced relaxation of the isolated SMV. 5-CT (1 μg kg(-1) min(-1), sc) also reduced blood pressure over 7 days. These findings suggest that 5-HT directly relaxes the SMV primarily through activation of the 5-HT7 receptor.

  20. 5-HT is a potent relaxant in rat superior mesenteric veins

    PubMed Central

    Watts, Stephanie W; Darios, Emma S; Seitz, Bridget M; Thompson, Janice M

    2015-01-01

    Serotonin (5-HT, 5-hydroxytryptamine) reduces blood pressure of the conscious rat when administered chronically (1 week). 5-HT does not directly relax isolated arteries, and microsphere experiments in 5-HT-infused rats suggested that 5-HT increased flow to the splanchnic bed. We hypothesized that 5-HT increased splanchnic flow because of direct venous relaxation; our focus was thus on the superior mesenteric vein (SMV) as an important vein in splanchnic circulation. Real-time RT-PCR, immunohistochemistry and Western analyses supported the predominant expression of the 5-HT2B and 5-HT7 receptor in the SMV. The SMV was mounted in tissue baths for measurement of isometric contraction. 5-HT caused a concentration-dependent relaxation of the endothelin-1 (ET-1)-contracted vein. The threshold of 5-HT-induced venous relaxation was significantly lower than for 5-HT-induced venous contraction (∼2 vs. 700 nmol/L, respectively). A series of serotonergic agonists established in their use of receptor characterization was tested, and the following rank order of potency found for agonist-induced relaxation (receptor selectivity): 5-CT (5-HT1/5-HT7)>5-HT = LP-44 (5-HT7)>PNU109291 (5-HT1D) = BW723C86 (5-HT2B). 8-OH-DPAT (5-HT1A/7), CP93129 (5-HT1B), mCPBG (5-HT3/4), AS19 (5-HT7) and TCB-2 (5-HT2A) did not relax the isolated vein. Consistent with these findings, two different 5-HT7 receptor antagonists SB 269970 and LY215840 but not the 5-HT2B receptor antagonist LY272015 nor the nitric oxide synthase inhibitor LNNA abolished 5-CT-induced relaxation of the isolated SMV. 5-CT (1 μg kg−1 min−1, sc) also reduced blood pressure over 7 days. These findings suggest that 5-HT directly relaxes the SMV primarily through activation of the 5-HT7 receptor. PMID:25692021

  1. Could the 5-HT1B receptor inverse agonism affect learning consolidation?

    PubMed

    Meneses, A

    2001-03-01

    Diverse evidence indicates that, the 5-HT system might play a role in learning and memory, since it occurs in brain areas mediating such processes and 5-HT drugs modulate them. Hence in this work, in order to explore further 5-HT involvement on learning and memory 5-HT1B receptors' role is investigated. Evidence indicates that SB-224289 (a 5-HT1B receptor inverse agonist) post-training injection facilitated learning consolidation in an associative autoshaping learning task, this effect was partially reversed by GR 127935 (a 5-HT1B/1D receptor antagonist), but unaffected by MDL 100907 (a 5-HT2A receptor antagonist) or ketanserin (a 5-HT1D/2A/7 receptor antagonist) at low doses. Moreover, SB-224289 antagonized the learning deficit produced by TFMPP (a 5-HT1A/1B/1D/2A/2C receptor agonist), GR 46611 (a 5-HT1A/1B/1D receptor agonist), mCPP (a 5-HT2A/2C/3/7 receptor agonist/antagonist) or GR 127935 (at low dose). SB-224289 did not alter the 8-OH-DPAT (a 5-HT1A/7 receptor agonist) learning facilitatory effect. SB-224289 eliminated the deficit learning produced by the anticholinergic muscarinic scopolamine or the glutamatergic antagonist dizocilpine. Administration of both, GR 127935 (5mg/kg) plus ketanserin (0.01 mg/kg) did not modify learning consolidation; nevertheless, when ketanserin dose was increased (0.1-1.0mg/kg) and SB-224289 dose was maintained constant, a learning facilitation effect was observed. Notably, SB-224289 at 1.0mg/kg potentiated a subeffective dose of the 5-HT1B/1D receptor agonist/antagonist mixed GR 127935, which facilitated learning consolidation and this effect was abolished by ketanserin at a higher dose. Collectively, the data confirm and extend the earlier findings with GR 127935 and the effects of non-selective 5-HT(1B) receptor agonists. Clearly 5-HT1B agonists induced a learning deficit which can be reversed with SB-224289. Perhaps more importantly, SB-224289 enhances learning consolidation when given alone and can reverse the deficits

  2. Potentiating action of MKC-242, a selective 5-HT1A receptor agonist, on the photic entrainment of the circadian activity rhythm in hamsters

    PubMed Central

    Moriya, T; Yoshinobu, Y; Ikeda, M; Yokota, S; Akiyama, M; Shibata, S

    1998-01-01

    Serotonergic projections from the midbrain raphe nuclei to the suprachiasmatic nuclei (SCN) are known to regulate the photic entrainment of circadian clocks. However, it is not known which 5-hydroxytryptamine (5-HT) receptor subtypes are involved in the circadian regulation. In order to verify the role of 5-HT1A receptors, we examined the effects of 5-{3-[((2S)-1,4-benzodioxan-2-ylmethyl)amino]propoxy}-1,3-benzodioxole HCl (MKC-242), a selective 5-HT1A receptor agonist, on photic entrainment of wheel-running circadian rhythms of hamsters.MKC-242 (3 mg kg−1, i.p.) significantly accelerated the re-entrainment of wheel-running rhythms to a new 8 h delayed or advanced light-dark cycle.MKC-242 (3 mg kg−1, i.p.) also potentiated the phase advance of the wheel-running rhythm produced by low (5 lux) or high (60 lux) intensity light pulses. In contrast, 8-hydroxy-dipropylaminotetralin (8-OH-DPAT)(5 mg kg−1, i.p.), a well known 5-HT1A/5-HT7 receptor agonist, only suppressed low intensity (5 lux) light-induced phase advances.The potentiating actions of MKC-242 on light pulse-induced phase advances were observed even when injected 20 or 60 min after the light exposure.The potentiating action of MKC-242 was antagonized by WAY100635, a selective 5-HT1A receptor blocker, but not by ritanserin, a 5-HT2/5-HT7 receptor blocker, indicating that MKC-242 is activating 5-HT1A receptors.Light pulse-induced c-fos expression in the SCN and the intergeniculate leaflet (IGL) were unaffected by MKC-242 (3 mg kg−1, i.p.).HPLC analysis demonstrated that MKC-242 (3 mg kg−1, i.p.) decreased the 5-HIAA content in the SCN.The present results suggest that presynaptic 5-HT1A receptor activation may be involved in the potentiation of photic entrainment by MKC-242 in hamsters. PMID:9863658

  3. Does genetic BDNF deficiency in rats interact with neurotransmitter control of prepulse inhibition? Implications for schizophrenia.

    PubMed

    van den Buuse, Maarten; Biel, Davina; Radscheit, Kathrin

    2017-04-03

    Several studies have suggested a role of BDNF in the development of schizophrenia. For example, post-mortem studies have shown significantly reduced levels of BDNF protein expression in the brain of schizophrenia patients. We investigated the relationship between reduced levels of BDNF in the brain and the regulation of prepulse inhibition (PPI), a behavioral endophenotype of schizophrenia. We used BDNF heterozygous mutant rats which display a 50% decrease of mature BDNF protein levels. Previously, we observed normal baseline PPI and responses to the dopamine D1/D2 receptor agonist, apomorphine, in these rats. Here, we focused on the effects of the NMDA receptor antagonist, MK-801, its interaction with mGluR2/3 and mGluR5 receptors, and the PPI response to serotonergic drugs. MK-801 administration caused a dose-dependent reduction of PPI and increase of startle amplitudes. Baseline PPI and the effect of 0.02-0.1mg/kg of MK-801 were not significantly altered in male or female BDNF heterozygous rats, although the MK-801-induced increase in startle levels was reduced. Co-treatment with the mGluR2/3 agonist, LY379,268, or the mGluR5 antagonist, MPEP, did not alter the effect of MK-801 on PPI in controls or BDNF mutant rats. Treatment with the serotonin-1A receptor agonist, 8-OH-DPAT, the serotonin-2A receptor agonist, DOI, or the serotonin releaser, fenfluramine, induced differential effects on PPI and startle but these effects were not different between the genotypes. These results show that a significant decrease of BDNF protein expression does not lead to reduced PPI at baseline or changes in the regulation of PPI via NMDA receptors or serotonergic mechanisms. These findings in a genetic rat model of BDNF deficiency do not support a role for similar reductions of BDNF levels in schizophrenia in the disruption of PPI, widely reported as an endophenotype of the illness. The potential implications of these results for our understanding of changes in PPI and BDNF

  4. Aviation spirit - past, present, and future

    NASA Technical Reports Server (NTRS)

    Dunstan, A E; Thole, F B

    1923-01-01

    The volatile fuel of the high-speed internal combustion engine has, in the past, consisted almost exclusively of the lighter distillates from crude petroleum. Alternative and supplementary fuels are discussed such as: tetraline, dekalin, alcohol, cyclo-hexenes.

  5. Effect of Flame Temperature and Fuel Composition on Sooting Tendency in a Research Combustor.

    DTIC Science & Technology

    1981-12-01

    fuel blends containing alkyl benzenes, methyl naphthalenes, tetralin and Indene were prepared with hydrogen contents ranging from 11.5 to 14.2 percent...must be added in larger quantities than methyl naphthalene. The S1 sensitivity for fuels containing alkyl benzenes was less at most operating...different concentrations of alkyl benzenes, methyl naphthalenes, tetralin, and indene, with hydrogen contents ranging from 11.5 to 14.2 percent, were burned

  6. Serotonin control of sleep-wake behavior.

    PubMed

    Monti, Jaime M

    2011-08-01

    in REMS that their wild-type counterparts. Direct infusion of the 5-HT(1A) receptor agonists 8-OH-DPAT and flesinoxan into the DRN significantly enhances REMS in the rat. In contrast, microinjection of the 5-HT(1B) (CP-94253), 5-HT(2A/2C) (DOI), 5-HT(3) (m-chlorophenylbiguanide) and 5-HT(7) (LP-44) receptor agonists into the DRN induces a significant reduction of REMS. Systemic injection of full agonists at postsynaptic 5-HT(1A) (8-OH-DPAT, flesinoxan), 5-HT(1B) (CGS 12066B, CP-94235), 5-HT(2C) (RO 60-0175), 5-HT(2A/2C) (DOI, DOM), 5-HT(3) (m-chlorophenylbiguanide) and 5-HT(7) (LP-211) receptors increases W and reduces SWS and REMS. Of note, systemic administration of the 5-HT(2A/2C) receptor antagonists ritanserin, ketanserin, ICI-170,809 or sertindole at the beginning of the light period has been shown to induce a significant increase of SWS and a reduction of REMS in the rat. Wakefulness was also diminished in most of these studies. Similar effects have been described following the injection of the selective 5-HT(2A) receptor antagonists volinanserin and pruvanserin and of the 5-HT(2A) receptor inverse agonist nelotanserin in rodents. In addition, the effects of these compounds have been studied on the sleep electroencephalogram of subjects with normal sleep. Their administration was followed by an increase of SWS and, in most instances, a reduction of REMS. The administration of ritanserin to poor sleepers, patients with chronic primary insomnia and psychiatric patients with a generalized anxiety disorder or a mood disorder caused a significant increase in SWS. The 5-HT(2A) receptor inverse agonist APD-125 induced also an increase of SWS in patients with chronic primary insomnia. It is known that during the administration of benzodiazepine (BZD) hypnotics to patients with insomnia there is a further reduction of SWS and REMS, whereas both variables tend to remain decreased during the use of non-BZD derivatives (zolpidem, zopiclone, eszopiclone, zaleplon). Thus

  7. Catalytic coal liquefaction. Quarterly report, October-December 1982

    SciTech Connect

    Weller, S.W.

    1983-01-01

    The catalysis of hydrogen transfer from tetralin to coal has been investigated in a tubing bomb and in an autoclave, in the absence of added hydrogen gas. On the basis of naphthalene production in tubing bomb experiments, many metals apparently increase hydrogen transfer from tetralin. Blank experiments with powdered catalyst but no coal indicate that only stannous chloride and ammonium heptamolybdate have a large effect. In the case of the molybdenum catalyst, even this effect is suspect, because blank runs with molybdate dispersed on an alumina carrier (itself non-catalytic) result in greatly increased dissociation of tetralin to naphthalene and gaseous hydrogen. Coal acts as a high-area carrier for impregnated catalyst. Thermodynamic considerations of tetralin dissociation are helpful in understanding significant differences between tubing bomb and autoclave results. When the gas:liquid volume ratio is relatively high, as in a tubing bomb, tetralin dissociation will be relatively small and equilibrium hydrogen pressure relatively high. The reverse may be true in an autoclave. Both factors lead to the expectation of higher coal conversion in a tubing bomb, in agreement with experiment.

  8. Fundamental studies of coal liquefaction. Quarterly report No. 8, July 1, 1993--October 1, 1993

    SciTech Connect

    Ross, D.S.

    1993-10-14

    In the last report the effects of water, tetralin, and argon were discussed as media during the heating of Illinois No. 6 coal. In studies in which the temperature was ramped from ambient to 460{degrees}C at 30{degrees}C/min particles were observed to shrink in the case of both water and tetralin, and first swell and then collapse back to particles with their starting shapes in the case of argon. The result with tetralin was expected, but that for water was not. Similarly, the results in argon were not in accord with some models of coal pyrolysis which suggest that coals fully liquefy when heated (Solomon, et al.). The work described here includes discussion of additional work with Illinois No. 6 coal with argon and water, and new work with n-undecane as medium.

  9. Alternative fuel production by catalytic hydroliquefaction of solid municipal wastes, primary sludges and microalgae.

    PubMed

    Lemoine, F; Maupin, I; Lemée, L; Lavoie, J-M; Lemberton, J-L; Pouilloux, Y; Pinard, L

    2013-08-01

    An alternative fuel production was investigated through catalytic hydroliquefaction of three different carbonaceous sources: solid municipal wastes (MW), primary sludges (PS), and microalgae (MA). The reaction was carried out under hydrogen pressure, at different temperatures (330, 380 and 450°C), with a Raney nickel catalyst and two different hydrogen donor solvents: a "fossil solvent" (tetralin) and a "green solvent" (2-methyl-hydro-furan). The feeds analyses (TDA-TGA, ICP-AES, lipids quantification) showed that MW and PS had similar characteristics and physico-chemical properties, but different from those of MA. The hydroliquefaction of these feeds allowed to obtain high oil yields, with a significant energetic value, similar to that of a bio-petroleum. 2-methyl-hydro-furan was more efficient than tetralin for the treatment of the strongly bio-degraded biomasses MW and PS, while better results were obtained with tetralin in the case of MA.

  10. Correction to Smith et al. (2013).

    PubMed

    Smith, Carl D; Piasecki, Christopher C; Weera, Marcus; Olszewicz, Joshua; Lonstein, Joseph S

    2015-08-01

    did increase anxiety-related behavior in postpartum females. However, BSTv infusion of idazoxan did not reproduce yohimbine's anxiogenic effects and anxiety was not reduced by peripheral or intra-BSTv clonidine. Because yohimbine is a weak 5HT1A receptor agonist, other groups of females received BSTv infusion of the 5HT1A receptor agonist 8OH-DPAT, but it did not alter their anxiety-related behavior. Lastly, levels of norepinephrine and serotonin in tissue punches from the BSTv did not differ between postpartum and diestrous rats, but serotonin turnover was higher in mothers. These results suggest that the impaired maternal behavior after BSTv infusion of yohimbine or idazoxan cannot both be readily explained by an increase in dams' anxiety, and that BSTv α2-autoreceptor modulation alone has little influence on anxiety-related behaviors in postpartum or diestrous rats.

  11. Mediation of 5-HT-induced external carotid vasodilatation in GR 127935-pretreated vagosympathectomized dogs by the putative 5-HT7 receptor

    PubMed Central

    Villalón, Carlos M; Centurión, David; Luján-Estrada, Miguel; Terrón, José A; Sánchez-López, Araceli

    1997-01-01

    The vasodilator effects of 5-hydroxytryptamine (5-HT) in the external carotid bed of anaesthetized dogs with intact sympathetic tone are mediated by prejunctional sympatho-inhibitory 5-HT1B/1D receptors and postjunctional 5-HT receptors. The prejunctional vasodilator mechanism is abolished after vagosympathectomy which results in the reversal of the vasodilator effect to vasoconstriction. The blockade of this vasoconstrictor effect of 5-HT with the 5-HT1B/1D receptor antagonist, GR 127935, unmasks a dose-dependent vasodilator effect of 5-HT, but not of sumatriptan. Therefore, the present study set out to analyse the pharmacological profile of this postjunctional vasodilator 5-HT receptor in the external carotid bed of vagosympathectomized dogs pretreated with GR 127935 (20 μg kg−1, i.v.).One-minute intracarotid (i.c.) infusions of 5-HT (0.330 μg min−1), 5-carboxamidotryptamine (5-CT; 0.010.3 μg min−1), 5-methoxytryptamine (1100 μg min−1) and lisuride (31000 μg min−1) resulted in dose-dependent increases in external carotid blood flow (without changes in blood pressure or heart rate) with a rank order of agonist potency of 5-CT>>5-HT⩾5-methoxytryptamine>lisuride, whereas cisapride (1001000 μg min−1, i.c.) was practically inactive. Interestingly, lisuride (mean dose of 85±7 μg kg−1, i.c.), but not cisapride (mean dose of 67±7 μg kg−1, i.c.), specifically abolished the responses induced by 5-HT, 5-CT and 5-methoxytryptamine, suggesting that a common site of action may be involved. In contrast, 1 min i.c. infusions of 8-OH-DPAT (33000 μg min−1) produced dose-dependent decreases, not increases, in external carotid blood flow and failed to antagonize (mean dose of 200±33 μg kg−1, i.c.) the agonist-induced vasodilator responses.The external carotid vasodilator responses to 5-HT, 5-CT and 5-methoxytryptamine were not modified by intravenous (i.v.) pretreatment with either saline, (±)-pindolol (4

  12. Combustion efficiency and altitude operational limits of three liquid hydrocarbon fuels having high volumetric energy content in a J33 single combustor

    NASA Technical Reports Server (NTRS)

    Stricker, Edward G

    1950-01-01

    Combustion efficiency and altitude operational limits were determined in a J33 single combustor for AN-F-58 fuel and three liquid hydrocarbon fuels having high volumetric energy content (decalin, tetralin, and monomethylnaphthalene) at simulated altitude and combustor inlet-air conditions. At the conditions investigated, the combustion efficiency for the four fuels generally decreased with an increase in volumetric energy content. The altitude operational limits for decalin and tetralin fuels were higher than for AN-F-58 fuel; monomethylnaphthalene fuel gave the lowest altitude operational limit.

  13. Steam pretreatment for coal liquefaction. [Monthly report], August 1, 1993--August 31, 1993

    SciTech Connect

    1993-09-10

    Rapid heating liquefaction of steam pretreated Illinois No.6 coal mixed with 13X zeolite was carried out this month. The pores of this zeolite retain pyridine during drying, but not enough to account for the low apparent yield of pyridine extract. Soxhlet extraction analysis of the product showed a significantly lower oil yield compared with 5A zeolite. This might be caused by retention of tetralin in 13x zeolite pores. Tetralin retention will be determined subsequently. A test of 4A zeolite is planned for next month. Aquathermolysis of model compound {beta}-benzylnaphthyl ether was carried out this month at high pressure (liquid water conditions). Analysis of the recovered products are now in progress.

  14. The study of synergistic effects of alcohols on the catalytic hydrogenation of brown coal

    SciTech Connect

    Kuznetsov, P.N.; Kuznetsova, L.I.; Kartseva, N.V.

    1998-12-31

    The hydrogenation of brown coal in methanol, ethanol and isopropanol containing medium in the presence of catalysts was studied. The effects of different catalysts, alcohols, the proportion between the quantity of hydrogen, alcohols and tetralin on the conversion of coal, product yields, composition and molecular weight of solubles were analyzed. The synergistic effects of the mixtures of methanol and ethanol with tetralin and with hydrogen on the conversion of brown coal were observed at 380 C and 430 C in the presence of supported Fe, Fe-Mo, Ni, and Co hydroxide catalysts. Small amounts of methanol and ethanol additives induced the improved coal swelling and conversion into soluble products with diminished molecular weight. Synergistic effect was found to depend on the catalyst concentration, hydrogen pressure and alcohol structure. Coal swelling, hydrogenation and alkylation reactions were evaluated. The nature of the promoting effect of alcohols on coal liquefaction is discussed.

  15. Coal transformation chemistry. First quarterly progress report, March 1, 1980-May 31, 1980

    SciTech Connect

    Stock, Leon M.; Alemany, L. B.; Handy, C. I.; King, H. -H.

    1980-01-01

    Considerable progress has been made on the development of a convenient procedure for the alkylation of Illinois No. 6 coal in liquid ammonia. The results are presented in summary in Section IIIB, Task 1 and in more detail in Section IVB. Work on the chemistry of the liquefaction reaction has led to the conclusion that phenolic compounds participate in free radical reactions in hydrogen donor solvents. Phenolic compounds and benzoic acid derivatives do not function as acid catalysts in their reactions with tetralin and other representative compounds. In addition, the reaction of styrene with tetralin at 400/sup 0/C has been shown to be a complex process involving rather deepseated chemical transformations. The results are presented in summary in Section IIIB, Task 3 and in more detail in Section IVC.

  16. Effect of various experimental parameters on the swelling and supercritical extraction properties of lignite

    SciTech Connect

    Hacimehmetoglu, S.; Sinag, A.; Tekes, A.T.; Misirlioglu, Z.; Canel, M.

    2007-07-01

    The original lignite sample, the samples swollen in dimethylsulfoxide (DMSO), dimethylformamide (DMF), pyridine, tetrahydrofuran (THF), acetone, ethylenediamine (EDA), N-methyl-2-pyrrolidone (NMP), tetrabutylammonium hydroxide (TBAH), the samples impregnated by ZnCl{sub 2} as catalyst and the samples both swollen in the solvents and impregnated by ZnCl{sub 2} were subjected to the supercritical toluene extraction and the effects of temperature, pressure, pre-swelling procedure, hydrogen donor solvent (tetralin), and catalyst on the extract yields were investigated.

  17. Mechanistic studies on the hydroliquefaction of Victorian brown coal and of coal derived products

    SciTech Connect

    Larkins, F.P.; Jackson, W.R.; Hertan, P.A.; Cassidy, P.J.; Marshall, M.; Rash, D.

    1983-01-01

    The reaction mechanisms of the hydroliquefaction of Victorian brown coal are studied. In particular, the catalytic effects of iron and tin-based catalyst systems are investigated. Samples were hydrogenated in a 70 mL rocking autoclave using a 1:1 slurry of coal and tetralin at an initial hydrogen pressure of 1-10 mPa for one hour at 385/sup 0/C. Conversions as a function of reaction temperature and initial hydrogen pressure are presented.

  18. Advanced Thermally Stable Coal-Derived Jet Fuels Compositional Factors Affecting Thermal Degradation of Jet Fuels

    DTIC Science & Technology

    1992-12-01

    cyclization of n-butylbenzene or similar compounds, followed by dehydrogenation, Eq. 3. They can also be formed from the Diels - Alder type reaction between...after 4 hours. Tetralin can also undergo, to a small extent, ring contraction [111 to form 1-methylindan (Eq.3B). In addition, the Diels - Alder type ...may be the attack of ethyl radical on biphenyl to form 2-ethylbiphenyl, followed by condensation , Eq. 9. The Diels - Alder reaction between ethylene and

  19. Jet fuel instability mechanisms

    NASA Technical Reports Server (NTRS)

    Daniel, S. R.

    1985-01-01

    The mechanisms of the formation of fuel-insoluble deposits were studied in several real fuels and in a model fuel consisting of tetralin in dodecane solution. The influence of addition to the fuels of small concentrations of various compounds on the quantities of deposits formed and on the formation and disappearance of oxygenated species in solution was assessed. The effect of temperature on deposit formation was also investigated over the range of 308-453 K.

  20. Low severity coal liquefaction promoted by cyclic olefins. Quarterly report, October 1996--December 1996

    SciTech Connect

    Curtis, C.W.

    1997-06-01

    The goal of this research is to develop a methodology for analyzing the reactivity of cyclic olefins in situ in a high temperature and high pressure infrared cell. The reactivities of naphthalene, decalin, tetralin, isotetralin, 1,2-dihydronaphthalene and 1,4-dihydronaphthalene have been studied at 230{degrees}C under ambient pressure and under 500 psig blankets of both nitrogen and hydrogen.

  1. Advanced direct liquefaction concepts for PETC generic units. Quarterly technical progress report, October 1992--December 1992

    SciTech Connect

    Not Available

    1993-02-01

    The reactivity of the THF insoluble fraction of the ashy resid component of Wilsonville recycle oil (WRO) during liquefaction of Black Thunder coal in tetralin was determined at 415{degrees}C and 60 minutes. The liquefaction runs were made by combining this material with Black Thunder coal at the same ratio used in the WRO coal runs. THF conversion and product distribution from liquefaction in tetralin in the presence of the THF insoluble fraction of the ashy resid were similar to results from liquefaction in WRO. THF conversion was greater than loot with an oil yield that was somewhat higher than in WRO. Differences in HC gas yield and H{sub 2} consumption were slight, while conversion and product distribution from liquefaction of Black Thunder coal in tetralin or in the WRO distillate were quite different. In both these solvents the 85--86% THF conversions were less than for runs in which the THF insoluble fraction of the ashy resid was present. This establishes that the THF insoluble fraction of the ashy resid is the reactive fraction of the WRO.

  2. Aromatics saturation over hydrotreating catalysts: Reactivity and susceptibility to poisons

    SciTech Connect

    Kokayeff, P.

    1994-12-31

    Aromatics saturation over hydrotreating catalysts has been investigated by processing a synthetic feedstock to which naphthalene, biphenyl, tetralin, and cyclohexylbenzene have been added as model aromatic compounds. The saturation reactions were successfully correlated with a kinetic model of consecutive first order reactions. The rates of saturation of the di-aromatics, naphthalene and biphenyl, were approximately 5--40 times faster than the rate of saturation of the mono-aromatics, tetralin and cyclohexylbenzene. The nature of the di-aromatic is a significant determinant of its reactivity for saturation. The rate of saturation of naphthalene is 10--20 times faster than the rate of saturation of biphenyl. The two mono-aromatics, tetralin and cyclohexylbenzene, exhibited nearly identical reactivities for saturation. An investigation of the effect of organo-nitrogen compounds on saturation activity revealed a very severe poisoning and attenuation of saturation activity. Since activity was recoverable upon the removal of the poisoning agent the chemical effect was conjectured to be due to adsorption of the poison on the active sites of the catalyst. The adsorption constants were determined for three model nitrogen compounds--quinoline, indole, and tert-butylamine. The poisoning action of an organo-nitrogen compound was found to be dependent on both basicity and chemical structure.

  3. Low severity coal liquefaction promoted by cyclic olefins. Quarterly report, July--September 1996

    SciTech Connect

    Curtis, C.W.

    1997-05-01

    The goal of this research is to develop a methodology for analyzing the reactivity of cyclic olefins in situ in a high temperature and high pressure infrared cell. Cyclic olefins, such as 1,4,5,8-tetrahydronaphthalene (isotetralin) and 1,4,5,8,9,10-hexahydroanthracene (HHA), are highly reactive donor compounds that readily donate their hydrogen to coal and model acceptors when heated to temperatures of 200 C and above. These donors are active donors in the low severity liquefaction of coal at 350 C as shown in the research performed in this project. The infrared studies are being performed in a high temperature infrared cell that was obtained from AABSPEC. Modifications to that cell have been made and have been reported in previous progress reports. The useful temperature range of the high temperature infrared cell has been extended to 230 C through the use of a high-boiling perfluorocarbon solvent. High temperature infrared analyses have been performed using isotetralin, tetralin, naphthalene, 1,4-dihydronaphthalene and 1,2-dihydronaphthalene. Stability studies have shown that naphthalene was quite stable at temperatures up to 230 C, as were tetralin, decalin and 1,4-dihydronaphthalene. High temperature FTIR analysis of isotetralin and 1,2-dihydronaphthalene reacted at elevated temperatures forming tetralin and 1,4-dihydronaphthalene, respectively. The results of stability studies are reported.

  4. Coal anion structure and chemistry of coal alkylation. Final report, March 1, 1979-February 29, 1980

    SciTech Connect

    Stock, L.M.

    1980-01-01

    In accord with Task 1, some ether cleavage reactions were carried out in two different media - potassium/naphthalene/tetrahydrofuran and potassium/ ammonia - so that the merits and demerits of the two methods could be compared. Preliminary results suggest that both systems yield the same products, and that the ammonia medium is more convenient to work with, because of the absence of by-products such as reduced naphthalenes and tetralin. Dialkyl ethers were found to be least reactive compounds while the benzyl and phenyl ethers were found to be most reactive, as would be expected. The reductive alkylation of coal was carried out in ammonia at 25/sup 0/C. The tetrahydrofuran solubility of the reaction product was surprisingly low. We have obtained additional /sup 13/C)/sup 1/H) nmr data for tetrahydrofuran-soluble butylated coal and some model compounds; obtained additional Styragel(R) chromatography data of tetrahydrofuran-soluble coal labelled with 98%-enriched butyl-1,1-d/sub 2/ iodide; and obtained /sup 2/D nmr spectra of all the deuterium-labelled, tetrahydrofuran-soluble coal products. In accord with Task 4, we have undertaken a review of the information now available concerning the nature of Illinois No. 6 coal. Also, the effects of organic additives on the exchange reactions between tetralin-d/sub 12/ and diphenyl-methane and on the thermal cleavage reactions of several model compounds in tetralin were investigated to probe the relationship between structure and reactivity. The exchange reaction can be accelerated by coal, asphaltene-preasphaltene fractions derived from coal, compounds with labile bonds, or compounds which can be reduced readily. The pyridine-insoluble coal product, acids, and bases are inactive toward the exchange reaction.

  5. Coal liquefaction in an inorganic-organic medium

    DOEpatents

    Vermeulen, Theodore; Grens, II, Edward A.; Holten, Ronald R.

    1982-01-01

    Improved process for liquefaction of coal by contacting pulverized coal in an inorganic-organic medium solvent system containing a ZnCl.sub.2 catalyst, a polar solvent with the structure RX where X is one of the elements O, N, S or P, and R is hydrogen or a lower hydrocarbon radical; the solvent system can contain a hydrogen donor solvent (and must when RX is water) which is immiscible in the ZnCl.sub.2 and is a hydroaromatic hydrocarbon, selected from tetralin, dihydrophenanthrene, dihydroanthracene or a hydrogenated coal derived hydroaromatic hydrocarbon distillate fraction.

  6. Coal liquefaction in an inorganic-organic medium. [DOE patent application

    DOEpatents

    Vermeulen, T.; Grens, E.A. II; Holten, R.R.

    Improved process for liquefaction of coal by contacting pulverized coal in an inorganic-organic medium solvent system containing a ZnCl/sub 2/ catalyst, a polar solvent with the structure RX where X is one of the elements O, N, S, or P, and R is hydrogen or a lower hydrocarbon radical; the solvent system can contain a hydrogen donor solvent (and must when RX is water) which is immiscible in the ZnCl/sub 2/ and is a hydroaromatic hydrocarbon selected from tetralin, dihydrophenanthrene, dihydroanthracene or a hydrogenated coal derived hydroaromatic hydrocarbon distillate fraction.

  7. Seven new sesquiterpenoids from the fruits of Schisandra sphenanthera.

    PubMed

    Tsai, Yao-Ching; Cheng, Yuan-Bin; Lo, I-Wen; Cheng, Ho-Hsi; Lin, Ching-Jie; Hwang, Tsong-Long; Kuo, Yuh-Chi; Liou, Shorong-Shii; Huang, Yi-Zsau; Kuo, Yao-Haur; Shen, Ya-Ching

    2014-07-01

    Fractionation of the EtOH extract from the fruits of Schisandra sphenanthera resulted in the isolation of seven new sesquiterpenoids, 1-7, in addition to the known metabolites 8-23. Among them, schiscupatetralin A (1) possesses an unprecedented structure with a CC bond between cuparenol and tetralin. The isolated new compounds were evaluated for their anti-HSV-1 and anti-inflammatory activities. The results revealed that compound 4 exhibited anti-HSV-1 activity, while compound 6 showed a significant anti-inflammatory activity.

  8. Co-processing of agriculture and biomass waste with coal

    SciTech Connect

    Stiller, A.H.; Dadyburjor, D.B.; Wann, J.P.

    1995-12-01

    Biomass and bio-processed waste are potential candidates for co-liquefaction with coal. Specific materials used here include sawdust and poultry manure. Liquefaction experiments were run on each of these materials, separately and with coal, using tetralin as solvent at 350{degrees}C and 1000 psi(cold) hydrogen pressure for 1h. Total conversion was monitored, as well as conversion to asphaltenes, oils and gases. All the biomass samples are converted to oils and gases under the reaction conditions. Poultry manure seems to convert coal more completely, and to produce more oils and gases, than conventional liquefaction.

  9. Annulation of Aromatic Imines via Directed C-H BondActivation

    SciTech Connect

    Thalji, Reema K.; Ahrendt, Kateri A.; Bergman, Robert G.; Ellman,Jonathan A.

    2005-04-14

    A directed C-H bond activation approach to the synthesis of indans, tetralins, dihydrofurans, dihydroindoles, and other polycyclic aromatic compounds is presented. Cyclization of aromatic ketimines and aldimines containing alkenyl groups tethered at the meta position relative to the imine directing group has been achieved using (PPh{sub 3}){sub 3}RhCl (Wilkinson's catalyst). The cyclization of a range of aromatic ketimines and aldimines provides bi- and tricyclic ring systems with good regioselectivity. Different ring sizes and substitution patterns can be accessed through the coupling of monosubstituted, 1,1- or 1,2-disubstituted, and trisubstituted alkenes bearing both electron-rich and electron-deficient functionality.

  10. The effects of hydrothermal pretreatment on the liquefaction of coal

    SciTech Connect

    Ross, D.S.; Hirschon, A. )

    1990-01-01

    The effects of aqueous pretreatment on coal and the benefits that can develop for liquefaction or mild gasification are areas of current interest. Most of the work has been conducted with water vapor, and current accounts include that of Bienkowski et al, who found that water vapor pretreatment enhanced liquefaction. Their work has focused on the use of liquid water at elevated temperatures, both as a probe into coal structure, and as a pretreatment for coal liquefaction. In the work summarized here, the authors examined the effects of hydrothermal pretreatment at 250{degree}C on conversion of Illinois No. 6 coal (PSOC 1098, and Argonne Premium Coal Bank samples) in tetralin.

  11. FeCl3-Catalyzed Tandem Prins and Friedel-Crafts Cyclization: A Highly Diastereoselective Route to Polycyclic Ring Structures.

    PubMed

    Ghosh, Arun K; Keyes, Chad; Veitschegger, Anne M

    2014-07-23

    Catalytic FeCl3 in the presence of 4Å molecular sieves has been shown to effect highly diastereoselective tandem Prins and Friedel-Crafts cyclization of substituted (E/Z)-6-phenylhex-3-en-1-ol and a variety of aldehydes to provide a range of polycyclic compounds in good to excellent yields. The reaction of an enantioenriched alcohol with an aldehyde provided the cyclization product without loss of optical activity. Furthermore, a Lewis acid catalyzed ring opening resulted in functionalized tetralin derivatives with multiple chiral centers.

  12. Steroidomimetic aminomethyl spiroacetals as novel inhibitors of the enzyme Δ8,7-sterol isomerase in cholesterol biosynthesis.

    PubMed

    Krojer, Melanie; Müller, Christoph; Bracher, Franz

    2014-02-01

    Grundmann's ketone is converted to a spiroacetal containing a 5-hydroxymethyl-5-nitro-1,3-dioxane moiety whose hydroxymethyl group can be esterified or directly substituted with primary and secondary amines. Among the resulting aminomethyl spiroacetals, several ones bearing diamino residues were found to be inhibitors of the enzyme Δ8,7-isomerase in cholesterol biosynthesis. The complex bicyclic building block derived from Grundmann's ketone could be replaced by a properly substituted tetraline scaffold, without noteworthy loss in activity. This opens the opportunity to perform further structural modifications for the design of new steroidomimetic inhibitors of human Δ8,7-isomerase.

  13. Effect of deoxygenation and prestressing on hydrocarbon fuel thermal stability

    NASA Technical Reports Server (NTRS)

    Bittker, D. A.

    1983-01-01

    A jet fuel thermal oxidation tester was used to study the effect of deoxygenation and deoxygenated prestressing on deposit formation when hydrocarbon fuels are thermally stressed. Four pure hydrocarbons (n-decane, cyclohexane, benzene and 1-hexene) and two mixtures (10 percent tetralin in n-dodecane and commercial Jet A) were used at temperatures of 250 C to 400 C. Deoxygenation decreased deposit formation for cycloheaxane but increased it for benzene. Deoxygenation decreased deposit formation for the two fuel mixtures at 250 C but had no effect at 350 C. Deoxygenated prestressing either increased or decreased deposit formation depending on the fuel used and the temperature.

  14. Investigation of mechanism of hydrogen transfer in coal hydrogenation. Quarterly progress report, June-August, 1980

    SciTech Connect

    Cronauer, D. C.; Ruberto, R. G.; McNeil, R. I.; Young, D. C.

    1980-09-01

    Hydrogen transfer experiments using Powhatan Number 5 Mine bituminous coal and deuterium labeled tetralin are underway. The rate of coal conversion, hydrogen transfer and site of hydrogen transfer are being measured. Preliminary results are consistent with those previously obtained with Kentucky and Illinois seam coals; namely, about 3.5 g of hydrogen is transferred per 100 g MAF coal at reactor conditions of 450/sup 0/C, 30 minutes and 30% feed coal in tetralin. At these conditions, about 73% conversion of coal to toluene solubles is achieved. Results at lower times (0 and 10 minutes) and temperatures (300, 350, and 400/sup 0/C) are also discussed. An evaluation of the techniques to measure hydrogen donor capacity has indicated that the best instrumental approach available to us is that of Seshadri et al in which /sup 13/C-NMR is used to quantify the level of hydroaromatics. Both GC/MS and group type MS techniques do not appear to be adequate for this purpose. Plans are being established to carry out solvent recycle and follow the effect of isomerization and adduction with the number of cycles.

  15. Rate limitations in coal/organic solvent interactions

    SciTech Connect

    Zieminski, G.H.

    1982-01-01

    Rate limitations in the extraction of tetralin-soluble material from Wyodak subbituminous coal were investigated at temperatures below those of coal pyrolysis. Intimate coal/tetralin contacting was conducted at 150 to 300/sup 0/C in a stirred batch contactor vessel at contacting times from 1/2 minute up to 24 hours, and in a high pressure Soxhlet apparatus at contacting times up to 725 hours. The yield of extracted coal material as a function of contacting time was determined from the amount of dissolved material in samples of the extract solution; total yields of up to 30% by weight of dry, ash-free (daf) coal were obtained. The extraction process could be well represented by a model based on three groups of soluble materials, in which each group was treated as a pseudo-single component. The first group (1.5-5.0% wt daf coal) extracts within the first minute of contacting, apparently unhindered by kinetic or mass transfer processes. Diffusion and weak bond breaking dominate the extraction of the second, intermediate rate, extract group (1.5-5.0% wt daf coal). The rate of extraction of the third group (5-24% wt daf coal) is kinetically controlled. The activation energies (0-10 kcal/mol) and rate coefficients (0.001-0.3 min/sup -1/) calculated from this model are well within the range that might be expected for the phenomena involved.

  16. Studies in coal liquefaction with application to the SRC and related processes. Quarterly report, August 1981-October 1981. [Using model compounds

    SciTech Connect

    Tarrer, A. R.; Guin, J. A.; Curtis, C. W.

    1981-01-01

    Model compound reactions were studied to evaluate the effects of mass transfer, solvent type, solvent blending, hydrogen partial pressure, temperature, reactant concentration, additive loading and its preparation, etc. Naphthalene hydrogenation and benzothiophene hydrodesulfurization were investigated under the conditions comparable to commercial coal liquefaction and related processes. Both of these reaction systems were observed to be surface reaction controlled under the reaction conditions used in this work. Certain aromatic compounds were observed to cause a reduction in the reaction rates of naphthalene and benzothiophene. Single stage coal dissolution was investigated using tetralin as a hydrogen donor solvent and a commercial cobalt-molybdate catalyst. A spinning basket system was developed to allow injection of the catalyst at a desired time in the reaction cycle. This catalyst injection technique proved to be reliable for the exploratory work done here. The degree of catalyst deactivation was rated by comparing the activities of the spent catalyst for model compound (naphthalene and cumene) reactivities relative to those of the fresh catalyst. No substantial reduction in deactivation was observed to result with delayed contacting of the catalyst with the coal-tetralin reaction mixture. The effect of reaction temperature on the initial rate of catalyst deactivation was also studied.

  17. Phase equilibrium in coal liquefaction processes. Final report

    SciTech Connect

    Chao, K.C.

    1984-08-01

    Gas-liquid equilibrium data have been determined in simulation of coal liquefaction process conditions in mixtures of light gases + heavy hydrocarbons to add to the accumulated data previously reported in EPRI AP-1593. The mixture systems newly investigated are: methane + 9,10 dihydrophenanthrene; hydrogen + methane + 1-methylnaphthalene; hydrogen + carbon dioxide + tetralin; hydrogen + carbon dioxide + 1-methynaphthalene; hydrogen + carbon dioxide + quinoline; nitrogen + tetralin, + n-hexadecane, + 1-methylnaphthalene, + quinoline, and + m-cresol. Correlations for the solubilities of methane and carbon dioxide have been developed from the data based on the use of solubility parameter. The solubility of hydrogen was correlated in EPRI AP-1593. Two equations of state are developed for the description of both the gas solubility and the vaporization of the heavy oil. The Chain-of-Rotators (COR) equation of state explicitly accounts for the rotational molecular motion contribution to the pressure of a fluid. The Cubic-Chain-of-Rotators (CCOR) equation is obtained upon simplifying the COR equation. Interaction constants in the CCOR equation have been determined for the light gases with the heavy hydrocarbons based on data from this project, and the constants are correlated. Equilibrium flash vaporization has been experimentally determined for three coal liquids and for their mixtures with hydrogen. The data are correlated with the CCOR equation of state. 74 figures, 46 tables.

  18. Liquid phase products and solid deposit formation from thermally stressed model jet fuels

    NASA Technical Reports Server (NTRS)

    Kim, W. S.; Bittker, D. A.

    1984-01-01

    The relationship between solid deposit formation and liquid degradation product concentration was studied for the high temperature (400 C) stressing of three hydrocarbon model fuels. A Jet Fuel Thermal Oxidation Tester was used to simulate actual engine fuel system conditions. The effects of fuel type, dissolved oxygen concentration, and hot surface contact time (reaction time) were studied. Effects of reaction time and removal of dissolved oxygen on deposit formation were found to be different for n-dodecane and for 2-ethylnaphthalene. When ten percent tetralin is added to n-dodecane to give a simpler model of an actual jet fuel, the tetralin inhibits both the deposit formation and the degradation of n-dodecane. For 2-ethylnaphthalene primary product analyses indicate a possible self-inhibition at long reaction times of the secondary reactions which form the deposit precursors. The mechanism of the primary breakdown of these fuels is suggested and the primary products which participate in these precursor-forming reactions are identified. Some implications of the results to the thermal degradation of real jet fuels are given.

  19. Direct liquefaction of plastics and coprocessing of coal with plastics

    SciTech Connect

    Huffman, G.P.; Feng, Z.; Mahajan, V.

    1995-12-31

    The objectives of this work were to optimize reaction conditions for the direct liquefaction of waste plastics and the coprocessing of coal with waste plastics. In previous work, the direct liquefaction of medium and high density polyethylene (PE), polypropylene (PPE), poly(ethylene terephthalate) (PET), and a mixed plastic waste, and the coliquefaction of these plastics with coals of three different ranks was studied. The results established that a solid acid catalyst (HZSM-5 zeolite) was highly active for the liquefaction of the plastics alone, typically giving oil yields of 80-95% and total conversions of 90-100% at temperatures of 430-450 {degrees}C. In the coliquefaction experiments, 50:50 mixtures of plastic and coal were used with a tetralin solvent (tetralin:solid = 3:2). Using approximately 1% of the HZSM-5 catalyst and a nanoscale iron catalyst, oil yields of 50-70% and total conversion of 80-90% were typical. In the current year, further investigations were conducted of the liquefaction of PE, PPE, and a commingled waste plastic obtained from the American Plastics Council (APC), and the coprocessing of PE, PPE and the APC plastic with Black Thunder subbituminous coal. Several different catalysts were used in these studies.

  20. Transalkylation reactions in fossil fuels and related model compounds

    SciTech Connect

    Farcasiu, M.; Forbus, T.R.; LaPierre, R.B.

    1983-02-01

    The alkyl substituents of high molecular weight polycyclic aromatic constituents of petroleum residues are transferable to exogenous monocyclic aromatics (benzene, toluene, o-xylene, etc.) by acid catalyzed (CF/sub 3/SO/sub 3/H) Friedel Crafts transalkylation. Analysis (GC-MS) of the volatile alkylated monocyclic aromatic products provides a method for the determination of the alkyl group content/structure of the starting fossil fuel mixture. Both model systems, using alkylated naphthalenes, phenanthrenes, pyrenes and dibenzothiophenes and demineralized shale oil or petroleum resid were studied. The model studies (alkyl chain length 2-10 carbons) revealed the following reaction pathways to predominate: (1) transalkylation rates/equilibria are independent of chain length; (2) n-alkyl groups are transfered without rearrangement or fragmentation; (3) reaction rate depends upon the aromatic moiety; (4) formation of dixylylmethanes via benzyl carbenium ions is significant (12 to 25% of product; and (5) significant minor products at longer reaction times are alkyl tetralins, tetralins, napthalenes and alkylated acceptors having a chain length reduced by (-CH/sub 2/-)/sub 4/.

  1. Coal liquefaction process streams characterization and evaluation: The preliminary evaluation of the kinetics of coal liquefaction distillation resid conversion

    SciTech Connect

    Klein, M.T.; Calkins, W.H.; Huang, He

    1994-02-01

    This study evaluated the use of a novel laboratory-scale batch reactor, designed by the University of Delaware, to study the kinetics of coal liquefaction resid reactivity. The short time batch reactor (STBR) is capable of conducting reactions at temperatures up to 450{degrees}C and pressures up to 2500 psi at well-defined reaction times from a few seconds to 30 min or longer. Sixty experiments were conducted with the STBR in this project. The products of the resid/tetralin/hydrogen reaction were separated by solubility, and several analytical procedures were used to evaluate the reaction products, including thermogravimetric analysis (TGA), gas chromatography (GC) and gas chromatography/mass spectrometry (GC/MS). Changes were monitored in the boiling ranges of the products, as a function of process conditions (time, temperature, and tetralin donor solvent-to-resid ratio), with and without catalysts. Two distillation resid samples were studied; Sample 1 is the resid of the second stage product stream from Wilsonville Run 259 which used Pittsburgh seam coal (Ireland mine) bituminous coal, and Sample 2 is the resid of the same streak from Wilsonville Run 260 which used Wyodak and Anderson (Black Thunder Mine) subbituminous coal. It was determined that the resid reactivity was different for the two samples studied. The results demonstrate that further development of this experimental method is warranted to empirically assess resid reactivity and to provide data for use in the construction of an empirical model of coal conversion in the direct liquefaction process.

  2. Low severity coal liquefaction promoted by cyclic olefins. Quarterly report, January--March 1992

    SciTech Connect

    Curtis, C.W.

    1992-10-01

    The naphthalene hydrogenation performed thermally at 350 and 400{degrees}C showed no reactivity of the naphthalene. The Molyvan L catalyst precursor promoted a small amount of hydrogenation of naphthalene at 400{degrees}C as shown in Table 1. Reaction at the higher initial pressure of 1250 psi resulted in slightly more conversion of naplithalene and a higher production of tetralin but no decalin was observed. The naphthalene hydrogenation reactions with Molyvan L without sulfur yielded a slightly higher % HYD of naphthalene than did the reactions with sulfur. Likewise, the reactions with an initial hydrogen pressure of 1250 psi yielded a higher % HYD of naphthalene than did the reaction with 1000 psi, regardless of whether sulfur was present. The Molyvan 822 catalyst precursor was substantially more active at 400{degrees}C than at 350{degrees}C as presented in Table 2. The presence of sulfur also promoted the activity of Molyvan 822 as a catalyst. Tetralin was the product and was produced in substantial quantities at 400{degrees}C. Molyvan 822 was much more active for naphthalene hydrogenation than was Molyvan L under equivalent conditions. For example, at 400{degrees}C with sulfur the reactions with Molyvan 822 produced 33.5% HYD while Molyvan L yielded 1.8% HYD. With Molyvan L, the less active catalyst, the effect tile mode of agitation (vertical or horizontal) was minimal.

  3. Low severity coal liquefaction promoted by cyclic olefins

    SciTech Connect

    Curtis, C.W.

    1992-01-01

    The naphthalene hydrogenation performed thermally at 350 and 400[degrees]C showed no reactivity of the naphthalene. The Molyvan L catalyst precursor promoted a small amount of hydrogenation of naphthalene at 400[degrees]C as shown in Table 1. Reaction at the higher initial pressure of 1250 psi resulted in slightly more conversion of naplithalene and a higher production of tetralin but no decalin was observed. The naphthalene hydrogenation reactions with Molyvan L without sulfur yielded a slightly higher % HYD of naphthalene than did the reactions with sulfur. Likewise, the reactions with an initial hydrogen pressure of 1250 psi yielded a higher % HYD of naphthalene than did the reaction with 1000 psi, regardless of whether sulfur was present. The Molyvan 822 catalyst precursor was substantially more active at 400[degrees]C than at 350[degrees]C as presented in Table 2. The presence of sulfur also promoted the activity of Molyvan 822 as a catalyst. Tetralin was the product and was produced in substantial quantities at 400[degrees]C. Molyvan 822 was much more active for naphthalene hydrogenation than was Molyvan L under equivalent conditions. For example, at 400[degrees]C with sulfur the reactions with Molyvan 822 produced 33.5% HYD while Molyvan L yielded 1.8% HYD. With Molyvan L, the less active catalyst, the effect tile mode of agitation (vertical or horizontal) was minimal.

  4. Investigation of sources, properties and preparation of distillate test fuels

    NASA Technical Reports Server (NTRS)

    Bowden, J. N.; Erwin, J.

    1983-01-01

    Distillate test fuel blends were generated for prescribed variations in composition and physical properties. Fuels covering a wide range in properties and composition which would provide a matrix of fuels for possible use in future combustion research programs were identified. Except for tetralin the blending components were all from typical refinery streams. Property variation blends span a boiling range within 150 C to 335 C, freezing point -23 C to -43 C, aromatic content 20 to 50 volume percent, hydrogen content 11.8 to 14.2 mass percent, viscosity 4 and 11 cSt (-20 C), and naphthalenes 8 and 16 volume percent. Composition variation blends were made with two base stocks, one paraffinic and the other napthenic. To each base stock was added each of three aromatic type fuels (alkyl benzenes, tetralin, and naphthalenes) for assigned initial boiling point, final boiling point, and hydrogen content. The hydrogen content was 13.5 mass percent for the paraffinic base stock blends and 12.5 mass percent and 11.5 mass percent for the naphthenic base stock blends. Sample 5-gallon quantities of all blends were prepared and analyzed.

  5. Mechanical similarities observed between polypropylene gels and molten polypropylenes

    NASA Astrophysics Data System (ADS)

    Oyer, A. J.; Carrillo, J.-M. Y.; Dobrynin, A. V.; Mackintosh, F. C.

    2013-03-01

    The gelation of syndiotactic and isotactic polypropylenes (sPP and iPP) was found when PPs were dissolved in 1,2,3,4-tetrahydronaphthalene (tetralin). Interestingly, it was found that the storage modulus of sPP-gel became higher than that of iPP-gel when PPs were dissolved in tetralin at low PP concentration (<40 wt%). The result was distinctly different from the result of the neat PPs without solvent, as it is widely known that the modulus of sPP is significantly lower than that of iPP. Moreover, by measuring the storage moduli of solid sPP and iPP as a function of temperature, it was found that, above the melting points of PP, the storage modulus of sPP became higher than that of iPP, which was similar to the behavior of the storage modulus observed in the dilute PP-gels. Such mechanical similarity between PP-gels and PP-melts was also observed within iPP samples with different molecular weights. From these experimental results, it was considered that the amorphous phase of PP had profound influence on the mechanical properties of PP-gels at low PP concentration (<40 wt%), while the crystalline phase of PP had a major impact on the mechanical properties of PP-gels at relatively higher PP concentration (>40 wt%).

  6. Solvent effects on polymer sorting of carbon nanotubes with applications in printed electronics.

    PubMed

    Wang, Huiliang; Hsieh, Bing; Jiménez-Osés, Gonzalo; Liu, Peng; Tassone, Christopher J; Diao, Ying; Lei, Ting; Houk, Kendall N; Bao, Zhenan

    2015-01-07

    Regioregular poly(3-alkylthiophene) (P3AT) polymers have been previously reported for the selective, high-yield dispersion of semiconducting single-walled carbon nanotubes (SWCNTs) in toluene. Here, five alternative solvents are investigated, namely, tetrahydrofuran, decalin, tetralin, m-xylene, and o-xylene, for the dispersion of SWCNTs by poly(3-dodecylthiophene) P3DDT. The dispersion yield could be increased to over 40% using decalin or o-xylene as the solvents while maintaining high selectivity towards semiconducting SWCNTs. Molecular dynamics (MD) simulations in explicit solvents are used to explain the improved sorting yield. In addition, a general mechanism is proposed to explain the selective dispersion of semiconducting SWCNTs by conjugated polymers. The possibility to perform selective sorting of semiconducting SWCNTs using various solvents provides a greater diversity of semiconducting SWCNT ink properties, such as boiling point, viscosity, and surface tension as well as toxicity. The efficacy of these new semiconducting SWCNT inks is demonstrated by using the high boiling point and high viscosity solvent tetralin for inkjet-printed transistors, where solvent properties are more compatible with the inkjet printing head and improved droplet formation.

  7. Hydrocarbons identified in extracts from estuarine water accommodated no. 2 fuel oil by gas chromatography-mass spectrometry

    NASA Technical Reports Server (NTRS)

    Lewis, B. W.; Walker, A. L.; Bieri, R. H.

    1974-01-01

    Results are presented on a computerized gas chromatograph-mass spectrometer analysis of methylene chloride and n-heptane extracts of a No. 2 fuel oil accommodated estuarine water sample. The analytical method is briefly described, and the limitations on the identifications are categorized. Some attempt was made to determine major and trace constituents in the water accommodate. Altogether 66 hydrocarbon compounds were identified specifically, and 75 compounds were partially identified. Seven compounds could be recognized as major constituents of the water accommodated oil and ten were present only as traces. The aromatic compounds found were alkyl benzenes, naphthalene, tetralin, indane, biphenyl, fluorene, anthracene, and some of their alkyl substituted isomers in the range of carbon numbers C7 to C15. Four n-alkanes, C10 to C13, were found along with four other assorted hydrocarbons.

  8. Oligomer formation in the radiation-induced polymerization of styrene

    NASA Astrophysics Data System (ADS)

    Harayma, Hiroshi; Al-Sheikhly, Mohamad; Silverman, Joseph

    2003-12-01

    Analyses of the oligomers formed in radiation-induced polymerization of purified styrene were performed. The principal dimeric products were cis- and trans-diphenyl-cyclobutane with a relatively small amount of 1-phenyltetralin; the trimeric products were the optical isomers of 1-phenyl-4-[1'-phenylethyl-(1')]-tetralin in gamma-ray and 60 MeV proton irradiation. Oligomer formation increased with increasing dose, but more gradually than the linear formation of high polymer with dose. The yield was 0.25-3.1 μmol/J at low doses and decreased to an asymptotic value of 0.15 at higher doses. It appears that oligomers act as chain transfer agents during the polymerization reaction which would account for the observed decrease in molecular weight of the high polymer with increase in dose. Although the thermal and radiation-induced polymerization of styrene have different initiation steps, the oligomers produced by both reactions are similar in composition.

  9. Fast-growing acacia as an example of a vegetable source for synthetic liquid fuel

    SciTech Connect

    Paushkin, Ya.M.; Gorlov, E.G.; Alaniya, V.P.

    1987-07-01

    The liquefaction of biomass, employing acacia sawdust, is described. Tests were conducted in a 1-liter vibratory autoclave at 26 vibrations per minute. The solvents used were tetralin, o-xylene, and decalin. The tests were conducted to evaluate the possibility of producing different hydrocarbons from acacia by alternative liquefaction processes (extraction under supercritical conditions or in a hydrogen donor medium). Gas and liquid fractions were comparatively determined for the different solvents and for their different ratios by chromatographic analysis. Optimum weight ratios and temperatures were established. It was concluded that thermal liquefaction of acacia can produce a broad gamut of different hydrocarbons, depending on solvent type and the liquefaction conditions, which can serve as motor fuel components or raw material for petrochemical synthesis.

  10. Bio oil synthesis by coupling biological biomass pretreatment and catalytic hydroliquefaction process.

    PubMed

    Hamieh, S; Beauchet, R; Lemee, L; Toufaily, J; Koubaissy, B; Hamieh, T; Pouilloux, Y; Pinard, L

    2014-03-01

    The bio-oil synthesis from a mixture of wastes (7wt.% straw, 38wt.% wood, and 45wt.% grass) was carried out by direct liquefaction reaction using Raney Nickel as catalyst and tetralin as solvent. The green wastes were biologically degraded during 3 months. Longer the destructuration time; higher the yield into oil is. Biological pretreatment of green wastes promotes the liquefaction process. Among the components of degraded biomass, Humin, the major fraction (60-80wt.%) that was favored by the biological treatment, yields to a bio oil extremely energetic with a HHV close to biopetroleum (40MJ kg(-1)), contrariwise, Fulvic acids (2-12wt.%), the minor fraction is refractory to liquefaction reaction.

  11. The 2.5-diacyl-1,4-dimethylbenzenes: Examples of bisphotoenol equivalents

    NASA Technical Reports Server (NTRS)

    Meador, Michael A.

    1987-01-01

    The photochemistry of 2,5-dibenzoyl(DBX)-and 2,5-diacetyl-1,4-dimethylbenzene (DAX) has been investigated. Both compounds readily undergo photoenolization similar to 0-alkylphenyl ketones. However, unlike 0-alkylphenyl ketones DAX and DBX are each capable of undergoing two tandem photoenolizations. Photoenols derived from o-alkylphenyl ketones have been successfully trapped with Diels-Alder dienophiles to provide a convenient synthesis of substituted tetralins. Similarly, Diels-Alder trapping of DBX photoenils afforded substituted tetra- and octahydro anthracenes. Further mainpulation of these photadducts provided the corresponding anthracenes in good yield. The photochemistry of DAX and DBX will be discussed, in particular their use in the synthesis of substituted anthracenes.

  12. Mechanistic studies on the hydroliquefaction of Victorian brown coal and of coal derived products

    SciTech Connect

    Larkins, F.P.; Cassidy, P.J.; Hertan, P.A.; Jackson, W.R.; Marshall, M.; Rush, D.

    1983-08-01

    The overall aim of our recent studies has been to obtain a more complete understanding of the mechanisms for the principal reactions which occur during the catalysed hydroliquefaction of low rank, high oxygen containing (ca. 25 wt% db) coals. The results of 70 ml batch autoclave studies with and without added catalysts on Victorian brown coal, on a number of different coal derived products and on related model ether compounds are discussed herein. More complete details of various aspects of this work may be found elsewhere. On the basis of these investigations a mechanism is proposed for the hydroliquefaction process which emphasises the role of catalysts in inhibiting repolymerisation reactions, the significance of interconvertibility of coal derived products and the importance of hydrogen donation from molecular hydrogen and the vehicle tetralin.

  13. Presence of hormonally-sensitive adenylate cyclase receptors in capillary-enriched fractions from rat cerebral cortex.

    PubMed

    Baca, G M; Palmer, G C

    1978-01-01

    The 10 000 g particulate fraction from capillary-enriched fractions isolated from rat cerebral cortex was shown to possess an adenylate cyclase highly sensitive to activation by sodium fluoride, norepinephrine, epinephrine, isoproterenol and dopamine. To a lesser extent histamine and three dopamine agonists, namely M-7 (5,6-dihydroxy-2-dimethylamino tetralin), ET-495 (methane sulfonate of pyribedil), and S-584 (metabolite of pyribedil) stimulated the enzyme preparation. The action of norepinephrine was blocked by propanolol while phenotolamine and haloperidol were relatively ineffective except at highest concentrations. Phentolamine and propanolol at only highest concentrations (10(-4) M) antagonized the action of dopamine. Haloperidol was seen to be a potent inhibitor of either dopamine- or dopamine agonist-sensitive adenylate cyclase. No effects on the enzyme were observed with methoxamine, octopamine or serotonin. These preliminary data suggest the presence of a mixed population of receptors for adenylate cyclase in rat brain capillaries.

  14. DEVELOPMENT OF CARBON PRODUCTS FROM LOW-RANK COALS

    SciTech Connect

    Edwin S. Olson

    2001-07-01

    The goal of this project is to facilitate the production of carbon fibers from low-rank coal (LRC) tars. To this end, the effect of demineralization on the tar yields and composition was investigated using high-sodium and high-calcium lignites commonly mined in North Dakota. These coals were demineralized by ion exchange with ammonium acetate and by cation dissolution with nitric acid. Two types of thermal processing were investigated for obtaining suitable precursors for pitch and fiber production. Initially, tars were produced by simple pyrolysis of the set of samples at 650 C. Since these experiments produced little usable material from any of the samples, the coals were heated at moderate temperatures (380 and 400 C) in tetralin solvent to form and extract the plastic material (metaplast) that forms at these temperatures.

  15. Influence of restricted diffusion on retrogressive free-radical reactions

    SciTech Connect

    Buchanan, A.C.; Britt, P.F. III; Thomas, K.B.

    1993-07-01

    The effects of restricted mass transport on retrogressive reaction pathways can be probed through the study of model compounds immobilized on silica surfaces. Silica-immobilized bibenzyl undergoes a free radical chain rearrangement reaction that converts the thermally labile bibenzylic linkage into a more refractory diphenylmethane-type linkage. The efficiency of this process was found to be quite sensitive to the structure of neighboring molecules on the surface. Co-immobilized naphthalene was more effective that co-immobilized tetralin (a hydrogen donor) in inhibiting the process, apparently by retarding the key hydrogen atom transfer step. The effect of the co-attached molecules on the retrogressive cyclization-dehydrogenation path as well as other reaction pathways for this complex system remain under investigation.

  16. Studies of the mechanisms of turbine fuel instability

    NASA Technical Reports Server (NTRS)

    Daniel, S. R.

    1983-01-01

    The formation of insoluble deposits in a Jet A, a Diesel, and a model fuel (1/10 v/v tetralin/dodecane) was studied. Experiments were conducted using glass containers at 394 K with an air/fuel ratio of 14/1. The effects of addition of ppm levels of various compounds on deposit formation were evaluated. Nitrogen heterocycles were shown to produce a basicity dependent acceleration of deposition. Thiols and thiophene were shown to increase deposition while sulfides and disulfides act as inhibitors. Copper metal and its salts also promote deposition. Results of various instrumental analyses of deposits and development of a high performance liquid chromatographic method for monitoring deposit precursors are discussed.

  17. Analogues of doxanthrine reveal differences between the dopamine D 1 receptor binding properties of chromanoisoquinolines and hexahydrobenzo[a]phenanthridines

    USGS Publications Warehouse

    Cueva, J.P.; Chemel, B.R.; Juncosa, J.I.; Lill, M.A.; Watts, V.J.; Nichols, D.E.

    2012-01-01

    Efforts to develop selective agonists for dopamine D 1-like receptors led to the discovery of dihydrexidine and doxanthrine, two bioisosteric ??-phenyldopamine-type full agonist ligands that display selectivity and potency at D 1-like receptors. We report herein an improved methodology for the synthesis of substituted chromanoisoquinolines (doxanthrine derivatives) and the evaluation of several new compounds for their ability to bind to D 1- and D 2-like receptors. Identical pendant phenyl ring substitutions on the dihydrexidine and doxanthrine templates surprisingly led to different effects on D 1-like receptor binding, suggesting important differences between the interactions of these ligands with the D 1 receptor. We propose, based on the biological results and molecular modeling studies, that slight conformational differences between the tetralin and chroman-based compounds lead to a shift in the location of the pendant ring substituents within the receptor. ?? 2011 Elsevier Ltd. All rights reserved.

  18. Compatibility of elastomers in alternate jet fuels

    NASA Technical Reports Server (NTRS)

    Kalfayan, S. H.; Fedors, R. F.; Reilly, W. W.

    1979-01-01

    The compatibility of elastomeric compositions of known resistance to aircraft fuels was tested for potential use in Jet A type fuels obtainable from alternate sources, such as coal. Since such fuels were not available at the time, synthetic alternate fuels were prepared by adding tetralin to a petroleum based Jet A type fuel to simulate coal derived fuels which are expected to contain higher amounts of aromatic and hydroaromatic hydrocarbons. The elastomeric compounds tested were based on butadiene-acrylonitrile rubber, a castable Thiokol polysulfide rubber, and a castable fluorosilicone rubber. Batches of various cross-link densities of these rubbers were made and their chemical stress relaxation behavior in fuel, air, and nitrogen, their swelling properties, and response to mechanical testing were determined.

  19. Fuel quality combustion analysis

    NASA Technical Reports Server (NTRS)

    Naegeli, D. W.; Moses, C. A.

    1979-01-01

    A high pressure research combustor operating over a wide range of burner inlet conditions was used to determine the effects of fuel molecular structure on soot formation. Six test fuels with equal hydrogen content (12.8%) were blended to stress different molecular components and final boiling points. The fuels containing high concentrations (20%) of polycyclic aromatics and partially saturated polycyclic structures such as tetralin, produced more soot than would be expected from a hydrogen content correlation for typical petroleum based fuels. Fuels containing naphthenes such as decalin agreed with the hydrogen content correlation. The contribution of polycyclic aromatics to soot formation was equivalent to a reduction in fuel hydrogen content of about one percent. The fuel sensitivity to soot formation due to the polycyclic aromatic contribution decreased as burner inlet pressure and fuel/air ratio increased.

  20. Analogues of doxanthrine reveal differences between the dopamine D1 receptor binding properties of chromanoisoquinolines and hexahydrobenzo[a]phenanthridines

    PubMed Central

    Cueva, Juan Pablo; Chemel, Benjamin R.; Juncosa, Jose I.; Lill, Markus A.; Watts, Val J.; Nichols, David E.

    2012-01-01

    Efforts to develop selective agonists for dopamine D1-like receptors led to the discovery of dihydrexidine and doxanthrine, two bioisosteric β-phenyldopamine-type full agonist ligands that display selectivity and potency at D1-like receptors. We report herein an improved methodology for the synthesis of substituted chromanoisoquinolines (doxanthrine derivatives) and the evaluation of several new compounds for their ability to bind to D1- and D2-like receptors. Identical pendant phenyl ring substitutions on the dihydrexidine and doxanthrine templates surprisingly led to different effects on D1-like receptor binding, suggesting important differences between the interactions of these ligands with the D1 receptor. We propose, based on the biological results and molecular modeling studies, that slight conformational differences between the tetralin and chroman-based compounds lead to a shift in the location of the pendant ring substituents within the receptor. PMID:22204903

  1. Emission FTIR analyses of thin microscopic patches of jet fuel residues deposited on heated metal surfaces

    NASA Technical Reports Server (NTRS)

    Lauer, J. L.; Vogel, P.

    1986-01-01

    The relationship of fuel stability to fuel composition and the development of mechanisms for deposit formation were investigated. Fuel deposits reduce heat transfer efficiency and increase resistance to fuel flow and are highly detrimental to aircraft performance. Infrared emission Fourier transform spectroscopy was chosen as the primary method of analysis because it was sensitive enough to be used in-situ on tiny patches of monolayers or of only a few molecular layers of deposits which generally proved completely insoluble in any nondestructive solvents. Deposits of four base fuels were compared; dodecane, a dodecane/tetralin blend, commercial Jet A fuel, and a broadened-properties jet fuel particularly rich in polynuclear aromatics. Every fuel in turn was provided with and without small additions of such additives as thiophene, furan, pyrrole, and copper and iron naphthenates.

  2. Development of Highly Reactive Nanometer Fe-Based Catalysts for Coal Liquefaction

    SciTech Connect

    Franz, James A.; Linehan, John C.; Matson, Dean W.; Smurthwaite, Tricia D.; Bekhazi, Jacky; Alnajjar, Mikhail S.

    2008-03-01

    This paper describes research involving the liquefaction of coal and the removal of oxygen from coal product constituents. Subbituminous Coal and early stage coal liquefaction products contain a substantial fraction of hydroxy-substituted aromatic hydrocarbons (phenols). An important reaction for upgrading of coal-derived organic materials is to remove oxygen groups. This paper describes the hydro-deoxygenation of naphthols and the liquefaction of subbituminous Wyodak coal using a catalyst prepared by in-situ sulfidation of nanometer scale 6-line iron ferrihydrite. The FeS catalyst enables the conversion of naphthol in substantial yields to tetralin and naphthalene at 400 degrees C in 9,10-dihydrophenanthrene. The kinetics and procedures to observe coal liquefaction and hydro-deoxygenation, and the effects of in-situ sulfidation on conversion kinetics are described.

  3. Comprehensive two-dimensional gas chromatography coupled to time-of-flight mass spectrometry of coal liquids produced during a coal liquefaction process

    SciTech Connect

    Jacqui F. Hamilton; Alistair. C. Lewis; Marcos Millan; Keith D. Bartle; Alan A. Herod; Rafael Kandiyoti

    2007-01-15

    Comprehensive two-dimensional gas chromatography (GC) coupled to time-of-flight mass spectrometry (MS) has been applied to the analysis of coal-derived liquids from the former British Coal Point-of-Ayr coal liquefaction plant. The feed to the hydrocracker and the resulting product were analyzed. The results refer almost exclusively to the plant-derived recycle solvent, known as the liquefaction solvent; the molecular mass range of the GC does not exceed that of the solvent. The method allows for the resolution of the numerous structural isomers of tetralin and methyl indan, one pair of hydrogen-donor (necessary for the dissolution of coal) and isomeric nondonor (that reduce the hydrogen donors) components of the recycle solvent. In addition, the n-alkanes that concentrate in the recycle solvent are easily observed in comparison with the results from one-dimensional GC-MS. 24 refs., 6 figs., 1 tab.

  4. Analysis of polydisperse fuel spray flame

    NASA Astrophysics Data System (ADS)

    Nave, Ophir; Lehavi, Yaron; Ajadi, Suraju; Gol'dshtein, Vladimir

    2017-02-01

    In this paper we analyzed the model of polydisperse fuel spray flame by using the sectional approach to describe the droplet-droplet interaction within the spray. The radii of the droplets are described by a probability density function. Our numerical simulations include a comparative analysis between three empirical droplet size distributions: the Rosin-Rammler distribution, the log-normal distribution and the Nakiyama-Tanasawa distribution. The log-normal distribution was found to produce a reasonable approximation to both the number and volume size distribution function. In addition our comparative analysis includes the application of the homotopy analysis method which yields convergent solutions for all values of the relevant parameters. We compared the above results to experimental fuel spray data such as {it{Tetralin}}, n-{it{Decane}}, and n-{it{Heptane}}.

  5. Computational methods of the Advanced Fluid Dynamics Model

    SciTech Connect

    Bohl, W.R.; Wilhelm, D.; Parker, F.R.; Berthier, J.; Maudlin, P.J.; Schmuck, P.; Goutagny, L.; Ichikawa, S.; Ninokata, H.; Luck, L.B.

    1987-01-01

    To more accurately treat severe accidents in fast reactors, a program has been set up to investigate new computational models and approaches. The product of this effort is a computer code, the Advanced Fluid Dynamics Model (AFDM). This paper describes some of the basic features of the numerical algorithm used in AFDM. Aspects receiving particular emphasis are the fractional-step method of time integration, the semi-implicit pressure iteration, the virtual mass inertial terms, the use of three velocity fields, higher order differencing, convection of interfacial area with source and sink terms, multicomponent diffusion processes in heat and mass transfer, the SESAME equation of state, and vectorized programming. A calculated comparison with an isothermal tetralin/ammonia experiment is performed. We conclude that significant improvements are possible in reliably calculating the progression of severe accidents with further development.

  6. Cooperative research in coal liquefaction. Final report, May 1, 1992--April 30, 1993

    SciTech Connect

    Huffman, G.P.

    1996-03-01

    Research on sulfate and metal (Mo, Sn) promoted Fe{sub 2}O{sub 3} catalysts in the current year focused on optimization of conditions. Parameters varied included temperature, solvent, solvent-to-coal ratio, and the effect of presulfiding versus in situ sulfiding. Oil yields were found to increase approximately proportionately with both temperature and solvent-to-coal ratio. The donor solvent, tetralin, proved to give better total conversion and oil yields than either 1-methylnaphthalene or Wilsonville recycle oil. A significant enhancement of both total liquefaction yields and oil yields from lignites and subbituminous coals has been achieved by incorporating iron into the coal matrix by cation exchange. A study has been conducted on the synthesis of iron, molybdenum, and tungsten catalysts using a laser pyrolysis technique.

  7. Characterization and reactivity of Pd Pt bimetallic supported catalysts obtained by laser vaporization of bulk alloy

    NASA Astrophysics Data System (ADS)

    Rousset, J. L.; Cadete Santos Aires, F. J.; Bornette, F.; Cattenot, M.; Pellarin, M.; Stievano, L.; Renouprez, A. J.

    2000-09-01

    Bimetallic Pd-Pt clusters produced by laser vaporization of bulk alloy have been deposited on high surface alumina. Energy dispersive X-ray (EDX) analysis and transmission electron microscopy (TEM) show that they have a perfectly well-defined stoichiometry and a narrow range of size. Therefore, they constitute ideal systems to investigate alloying effects towards reactivity. Pd-Pt alloys are already known for their applications in the hydrogenation of unsaturated hydrocarbons, especially aromatics, because this system is highly resistant to sulfur and nitrogen poisoning. In this context, the catalytic properties of this system have been investigated in the hydrogenation of tetralin in the presence of hydrogen sulfide. Preliminary results show that this model catalyst is more sulfur-resistant than each of the pure supported metals prepared by chemical methods.

  8. Pyrolysis of coal model compounds containing aromatic carboxylic acids: The role of carboxylic acids in cross-linking reactions in low-rank coal

    SciTech Connect

    Eskay, T.P.; Britt, P.F.; Buchanan, A.C. III

    1997-06-01

    The pyrolysis of 1-(3-carboxyphenyl)-2(4-biphenyl)ethane (1) diluted in 10-fold excess of naphthalene has been studied at 400 {degrees}C to investigate whether decarboxylation of aromatic carboxylic acids can lead to cross-linked products. The dominant mechanism for decarboxylation was found to be an acid-promoted ionic pathway that does not lead to cross-linking. However, a small amount of cross-linked products (i.e. naphthalene grafted onto decarboxylated 1) were formed. The yields of the cross-linked products were found to be decreased in the presence of a hydrogen donor solvent, tetralin, suggesting that these products were formed by a free-radical pathway. The mechanism for the formation of cross-linked products was proposed to occur from the formation and decomposition of anhydrides of 1 during pyrolysis.

  9. Coal Liquefaction by Using Dielectric Barrier Discharge Plasma

    NASA Astrophysics Data System (ADS)

    Wang, Qiuying; Wu, Peng; Gu, Fan

    2013-07-01

    An innovative method for coal liquefaction by using dielectric barrier discharge (DBD) plasma in a short reaction time was developed. Using tetralin as the reaction medium, DBD plasma as the energy source, and a reaction time of 10 min at 140°C, up to 10% of coal was converted to liquid material. The results showed the feasibility of coal's liquefaction by DBD plasma under relatively moderate conditions. Simultaneously, it was clarified that the effect of DBD plasma treatment was opposed to the thermal effect of heating. An acid plasma sheath could be formed on the coal powder surface in DBD conditions, liquefied reactions could be carried out in the absence of inorganic acid, and the products were nearly neutral and with low causticity.

  10. Spectral radiance measurements and calculated soot concentrations along the length of an experimental combustor

    NASA Technical Reports Server (NTRS)

    Norgren, C. T.; Ingebo, R. D.

    1976-01-01

    Radiometric data were obtained over a range of parametric test conditions at three positions along the length of an experimental combustor segment corresponding to the primary, intermediate, and dilution zones. The concentration of soot entrained in the combustion gases was calculated by a technique using spectral radiance measurements. Tests were conducted primarily with Jet A fuel, although limited data were taken with two fuels having higher aromatic content, diesel oil number 2 and a blend of 40 percent tetralin in Jet A fuel. Radiometric observation of the combustion gases indicated that the maximum total radiance peaked at the intermediate zone, which was located immediately upstream of the dilution holes. Soot concentrations calculated from optical measurements in the dilution zone compared favorably with those obtained by in situ gas sampling at the exhaust. The total radiance increased with the higher aromatic content fuels.

  11. Zinc chloride catalyzed decomposition of 1,2-dihydronaphthalene at 165 /sup 0/C, a coal-related model compound study

    SciTech Connect

    Beishline, R.R.; Gould, B.; Walker, E.B.; Stuart, D.K.; Schultzski, J.; Shigley, J.K.; Calvert, K.; Dalling, D.K.; Anderson, L.L.

    1982-04-23

    The zinc chloride catalyzed decomposition of 1,2-dihydronaphthalene (1) at 165 /sup 0/C produces dimers of 1, tetralin, and naphthalene. Zinc chloride functions as a Friedel-Crafts type catalyst by coordinating with a hydroxyl from a water molecule and releasing a proton which initiates a carbonium ion reaction. The stoichiometric role of water has been established by measuring the activity of the zinc chloride-water complex as a function of the degree of hydration of the zinc chloride. The activity maximum occurs at a zinc chloride/water mole ratio of 1:1. Deuterium tracer experiments corroborate the role of water and also verify that the reaction occurs by a carbonium ion mechanism. The carbonium ion nature of the reaction is also inferred by the structures of the products. The 300-MHz/sup 1/H NMR spectra of the dimer products are consistent with the previously reported structures of the compounds.

  12. Effect of fuel molecular structure on soot formation in gas turbine engines

    NASA Technical Reports Server (NTRS)

    Naegeli, D. W.; Moses, C. A.

    1980-01-01

    A high-pressure research combustor operating over a wide range of burner inlet conditions was used to determine the effects of fuel molecular structure on soot formation. Six test fuels with equal hydrogen content (12.8 percent) were blended to stress different molecular components and final boiling points. The fuels containing high concentrations (20 percent) of poly-cyclic aromatics and partially saturated polycyclic structures such as tetralin, produced more soot than would be expected from a hydrogen content correlation for typical petroleum based fuels. However, fuels containing naphthenes, such as decalin, agreed with the hydrogen content correlation. The contribution of polycylic aromatics to soot formation was equivalent to a reduction in fuel hydrogen content of about 1%. The fuel sensitivity to soot formation due to the polycyclic aromatic contribution decreased as burner inlet pressure and fuel/air ratio increased.

  13. Cyclic olefins as new hydrogen donor compounds for coal liquefaction

    SciTech Connect

    Bedell, M.W.; Curtis, C.W. )

    1990-01-01

    A new set of hydrogen donor compounds, cyclic olefins (CLO), has been evaluated to determine their effectiveness as hydrogen donors to coal. These cyclic olefins are hydroaromatic species which do not contain aromatic rings. The efficacy of these donors has been compared to conventional hydroaromatics. The CLO's under study are 1,4,5,8-tetrahydronaphthalene, also known as isotetralin, and 1,4,5,8,9,10-hexahydroanthracene. In this paper, the thermal and catalytic reactivity of the CLO's under nitrogen and hydrogen at coal liquefaction temperature is discussed. Results for the reactions of the CLO's and their conventional hydroaromatic analogues, e.g. tetralin, 9,10-dihydroanthracene, and octahydroanthracene, with Western Kentucky No. 9 coal are discussed.

  14. Applications of high pressure differential scanning calorimetry to aviation fuel thermal stability research

    NASA Technical Reports Server (NTRS)

    Neveu, M. C.; Stocker, D. P.

    1985-01-01

    High pressure differential scanning calorimetry (DSC) was studied as an alternate method for performing high temperature fuel thermal stability research. The DSC was used to measure the heat of reaction versus temperature of a fuel sample heated at a programmed rate in an oxygen pressurized cell. Pure hydrocarbons and model fuels were studied using typical DSC operating conditions of 600 psig of oxygen and a temperature range from ambient to 500 C. The DSC oxidation onset temperature was determined and was used to rate the fuels on thermal stability. Kinetic rate constants were determined for the global initial oxidation reaction. Fuel deposit formation is measured, and the high temperature volatility of some tetralin deposits is studied by thermogravimetric analysis. Gas chromatography and mass spectrometry are used to study the chemical composition of some DSC stressed fuels.

  15. Direct use of methane in coal liquefaction

    DOEpatents

    Sundaram, M.S.; Steinberg, M.

    1985-06-19

    This invention relates to a process for converting solid carbonaceous material, such as coal, to liquid and gaseous hydrocarbons utilizing methane, generally at a residence time of about 20 to 120 minutes at a temperature of 250 to 750/sup 0/C, preferably 350 to 450/sup 0/C, pressurized up to 6000 psi, and preferably in the 1000 to 2500 psi range, preferably directly utilizing methane 50 to 100% by volume in a mix of methane and hydrogen. A hydrogen donor solvent or liquid vehicle such as tetralin, tetrahydroquinoline, piperidine, and pyrolidine may be used in a slurry mix where the solvent feed is 0 to 100% by weight of the coal or carbonaceous feed. Carbonaceous feed material can either be natural, such as coal, wood, oil shale, petroleum, tar sands, etc., or man-made residual oils, tars, and heavy hydrocarbon residues from other processing systems. 1 fig.

  16. Direct use of methane in coal liquefaction

    DOEpatents

    Sundaram, Muthu S.; Steinberg, Meyer

    1987-01-01

    This invention relates to a process for converting solid carbonaceous material, such as coal, to liquid and gaseous hydrocarbons utilizing methane, generally at a residence time of about 20-120 minutes at a temperature of 250.degree.-750.degree. C., preferably 350.degree.-450.degree. C., pressurized up to 6000 psi, and preferably in the 1000-2500 psi range, preferably directly utilizing methane 50-100% by volume in a mix of methane and hydrogen. A hydrogen donor solvent or liquid vehicle such as tetralin, tetrahydroquinoline, piperidine, and pyrolidine may be used in a slurry mix where the solvent feed is 0-100% by weight of the coal or carbonaceous feed. Carbonaceous feed material can either be natural, such as coal, wood, oil shale, petroleum, tar sands, etc., or man-made residual oils, tars, and heavy hydrocarbon residues from other processing systems.

  17. Fundamentals of coal depolymerization: an experimental and statistical correlative model of the effects of temperature and solvent on free radicals in coal. Quarterly report, October 1-December 31, 1980

    SciTech Connect

    Petrakis, L; Grandy, D W; Jones, G L

    1981-01-01

    In this project we are attempting to develop information as to the nature and possible role of free radicals in the depolymerization of coal under hydroliquefaction conditions. It is generally assumed that free radical chemistry plays an important role in the liquefaction of coal. Central in our work has been the use of a specially designed high pressure/high temperature electron spin resonance cavity that allows us to quantitatively monitor free radicals in coal 2 to 4 minutes after the heating cycle is initiated. The free radical concentration has been measured quantitatively and repetitively at these various sets of conditions. The heating time has been restricted to three minutes, gas pressure to 1600 psi and the gas used is hydrogen. The main conclusions from this work include the following: in general, the coal free radicals are quenched in the naphthalene < SRC-II heavy distillate < tetralin. The observed free radical concentration depends on the competing effects of free radical formation and free radical quenching, the latter being both temperature and solvent dependent. The free radical concentration of the liquefaction slurry generally increases with increasing temperature. The rate of quenching of free radicals by SRC-II heavy distillate is closer to that of tetralin at lower temperatures and approaches that of naphthalene at the higher temperature. From the results of the full correlative model, we find that temperature, solvent and residence time and their interactions account for about 90% of the effects noted in the free radical concentration. The correlative model represents the experimental results within the reproducibility of the data.

  18. Fundamental studies of coal liquefaction

    SciTech Connect

    Not Available

    1995-01-01

    The authors have examined the pyrolysis of Argonne samples of Wyodak and Illinois No. 6 coal in argon, undecane, Tetralin, and water. The effects of the pyrolysis on individual particles of coal were monitored visually in a cell with diamond windows capable of operation to temperature and pressures in excess of 500{degrees}C and 3000 psi. The changes in the particles from ambient to 460{degrees}C were recorded in real time on video tape, and images were then taken from the tape record and analyzed. The study showed that in argon both coals developed tars at 350{degrees}-370{degrees}C. The tars then quickly evaporated, leaving core particles remarkably similar in size and shape to the initial particles. These observations suggest that coal does not melt nor become fully liquid when heated. Nor does the softened coal undergo crosslinking to generate coke. Rather the simple loss of volatiles leaves behind the core residue as coke. Contrary to the common view, there appears to be no link between the bond-breaking processes yielding tar and the interaction of the coal with H-donors leading to liquefaction. Water as a medium was surprising in its effect. Both coals began to shrink at 300{degrees}-350{degrees}C, with the effect appearing to be more of an erosion rather than a uniform loss of substance as seen in Tetralin. The Wyodak continued to shrink to 460{degrees}C to about half its initial size. With the Illinois No. 6 coal, however, the process reversed at around 420{degrees}C, and the particles appeared to grow with the evolution of a tar, continuing to 460{degrees}C. The authors submit that this final observation is evidence for hydrothermal synthesis of hydrocarbons at these conditions.

  19. Molecular catalytic coal liquid conversion. Quarterly report

    SciTech Connect

    Stock, L.M.; Yang, Shiyong

    1995-03-31

    In this Quarter, the research was focused continually on the two general tasks: Task 1, molecular organometallic catalysts for hydrogenation and Task 2, organic base catalysts for arene hydrogenation and the hydrotreating of the coal liquids. With regards to Task 1, the biphase catalyst system, [1,5-HDRhCI]{sub 2}/buffer, was investigated in detail for the hydrogenation of naphthalene or tetralin to decalin under low pressure of H{sub 2} at room temperature. The influence of various factors such as the amount of the phase transfer regent, the volume ratio of the organic phase to the aqueous phase, the pH value and compositions of the buffer solution as well as the solvents on the reaction process was investigated systematically. It was found that the rhodium catalyst works well under biphase conditions rather than under phase transfer conditions. Apparently, the surfactant molecules negatively affect the catalytic activity of the rhodium catalyst. The pH values and the compositions of the buffers in the aqueous phase are critical in the system. The best buffer solution is composed of hydrion with its pH of 7.4--7.6. In addition to tetralin, the Rh catalyst is also effective for the hydrogenation of other unactivated aromatic hydrocarbons such as toluene, n-butylbenzene etc. In addition, the turnover numbers of the catalyst can reach 200, but its performance needs to be improved further for practical applications. The work on this issue is currently underway. Task 2 was focused on the hydrotreating of coal liquid (VSOH) catalyzed by Catalyst 2 and Catalyst 5. Good results were achieved on this issue. Catalyst 5 was found to be a more effective catalyst for the hydrotreating of coal liquid than Catalyst 2. The coal liquid was hydrotreated to give a clear yellow liquid under relative mild conditions (1000 psi of hydrogen and 200C) if only 16 mol% of the Catalyst 5 was employed.

  20. The effect of selective solvent absorption on coal conversion. Final technical report

    SciTech Connect

    Larsen, J.W.

    1993-11-01

    Using a pair of different recycle oils from Wilsonville and {sup 1}H NMR, {sup 13}C NMR, gel permeation (GPC) chromatography, high pressure liquid chromatography (HPLC), and elemental analysis, no significant differences were observed between the composition of the recycle oil and that portion of the oil not absorbed by the coal. For these complex mixtures, coals are not selective absorbants. Since most of the heteroatoms responsible for most of the specific interactions have been removed by hydrogenolyses, this is perhaps not surprising. To address the issue of the role of hydrogen bond donors in the reused as hydrogen donor coal, tetralin and 2-t-butyltetralin were used as hydrogen donor solvents. This work is reported in detail in Section 2. The basic idea is that the presence of the t-butyl group on the aromatic ring will hinder or block diffusion of the hydrogen donor into the coal resulting in lower conversions and less hydrogen transferred with 2-t-butyltetralin than with tetralin. Observed was identical amounts of hydrogen transfer and nearly identical conversions to pyridine solubles for both hydrogen donors. Diffusion of hydrogen donors into the coal does not seem to play a significant role in coal conversion. Finally, in Section 3 is discussed the unfavorable impact on conversion of the structural rearrangements which occur when Illinois No. 6 coal is swollen with a solvent. We believe this rearrangement results in a more strongly associated solid leading to the diminution of coal reactions. Hydrogen donor diffusion does not seem to be a major factor in coal conversion while the structural rearrangement does. Both areas warrant further exploration.

  1. Competing reaction channels in IR-laser-induced unimolecular reactions

    SciTech Connect

    Berman, M.R.

    1981-01-01

    The competing reaction channels in the unimolecular decomposition of two molecules, formaldehyde and tetralin were studied. A TEA CO/sub 2/ laser was used as the excitation source in all experiments. The dissociation of D/sub 2/CO was studied by infrared multiphoton dissociation (MPD) and the small-molecule nature of formaldehyde with regard to MPD was explored. The effect of collisions in MPD were probed by the pressure dependence of the MPD yield and ir fluorescence from multiphoton excited D/sub 2/CO. MPD yield shows a near cubic dependence in pure D/sub 2/CO which is reduced to a 1.7 power dependence when 15 torr of NO is added. The peak amplitude of 5 ..mu..m ir fluorescence from D/sub 2/CO is proportional to the square of the D/sub 2/CO pressure in pure D/sub 2/CO or in the presence of 50 torr of Ar. Results are explained in terms of bottlenecks to excitation at the v = 1 level which are overcome by a combination of vibrational energy transfer and rotational relaxation. The radical/molecule branching ratio in D/sub 2/CO MPD was 0.10 +- 0.02 at a fluence of 125 J/cm/sup 2/ at 946.0 cm/sup -1/. The barrier height to molecular dissociation was calculated to be 3.6 +- 2.0 kcal/mole below the radical threshold or 85.0 +- 3.0 kcal/mole above the ground state of D/sub 2/CO. In H/sub 2/CO, this corresponds to 2.5 +- 2.0 kcal/mole below the radical threshold or 83.8 +- 3.0 kcal/mole above the ground state. Comparison with uv data indicate that RRKM theory is an acceptable description of formaldehyde dissociation in the 5 to 10 torr pressure range. The unimolecular decomposition of tetralin was studied by MPD and SiF/sub 4/ - sensitized pyrolysis. Both techniques induce decomposition without the interference of catalytic surfaces. Ethylene loss is identified as the lowest energy reaction channel. Dehydrogenation is found to result from step-wise H atom loss. Isomerization via disproportionation is also identified as a primary reaction channel.

  2. 2nd dimensional GC-MS analysis of sweat volatile organic compounds prepared by solid phase micro-extraction.

    PubMed

    Choi, Mi-Jung; Oh, Chang-Hwan

    2014-01-01

    The characteristics of an individual's odor from sweat, breath and skin provide important information for criminal tracking in field of forensic science. Solid phase micro-extraction gas chromatography/mass spectrometry (SPME-GC/MS) was used to determine human sweat volatile organic compounds (VOCs) profiles. The mass spectrometric analysis (with electron impact mode) followed by 2nd dimensional separation with two different GC columns (one polar and one relatively nonpolar) connected in parallel were used to identify the 574 compounds from sweat samples. The components included alcohols, aldehydes, aliphatics/aromatics, carboxylic acids, esters, ketones, and other organic compounds (amides/amines, thio/thioesters, oxide, sulfides, nitro compounds). Of these compounds, 1-tridecanol, 1,3-bis(1,1-dimethyl ethyl)-benzene, 4,4'-(1-methylethylidene) bis-phenol and 7-acetyl-6-ethyl-1,1,4,4,-tetramethyl-tetraline were common components in all donor's sweat volatile samples. Age-related specific compounds were also detected. The results suggest that characteristic volatile profiles of human sweat emanations could provide the valuable information to forensic scientists.

  3. Total Synthesis and Stereochemical Assignment of Delavatine A: Rh-Catalyzed Asymmetric Hydrogenation of Indene-Type Tetrasubstituted Olefins and Kinetic Resolution through Pd-Catalyzed Triflamide-Directed C-H Olefination.

    PubMed

    Zhang, Zhongyin; Wang, Jinxin; Li, Jian; Yang, Fan; Liu, Guodu; Tang, Wenjun; He, Weiwei; Fu, Jian-Jun; Shen, Yun-Heng; Li, Ang; Zhang, Wei-Dong

    2017-03-08

    Delavatine A (1) is a structurally unusual isoquinoline alkaloid isolated from Incarvillea delavayi. The first and gram-scale total synthesis of 1 was accomplished in 13 steps (the longest linear sequence) from commercially available starting materials. We exploited an isoquinoline construction strategy and developed two reactions, namely Rh-catalyzed asymmetric hydrogenation of indene-type tetrasubstituted olefins and kinetic resolution of β-alkyl phenylethylamine derivatives through Pd-catalyzed triflamide-directed C-H olefination. The substrate scope of the first reaction covered unfunctionalized olefins and those containing polar functionalities such as sulfonamides. The kinetic resolution provided a collection of enantioenriched indane and tetralin-based triflamides, including those bearing quaternary chiral centers. The selectivity factor (s) exceeded 100 for a number of substrates. These reactions enabled two different yet related approaches to a key intermediate 28 in excellent enantiopurity. In the synthesis, the triflamide served as not only an effective directing group for C-H bond activation but also a versatile functional group for further elaborations. The relative and absolute configurations of delavatine A were unambiguously assigned by the syntheses of the natural product and its three stereoisomers. Their cytotoxicity against a series of cancer cell lines were evaluated.

  4. Lignin-assisted coal depolymerization. [Final] technical report, September 1, 1991--August 31, 1992

    SciTech Connect

    Lalvani, S.B.; Muchmore, C.B.; Koropchak, J.A.; Kim, Jong Won

    1992-12-31

    Liquefaction of an Illinois bituminous and a caustic lignin was studied in an initial hydrogen pressure of 140 psig. Experiments were conducted in the temperature range of 325-375{degree}C in tetralin. The addition of lignin to coal was found to be synergistic in that it significantly improves the quality and yield of the liquid products obtained. Kinetic data for coal conversion enhancement due to lignin addition were obtained. A mathematical model describing the reaction chemistry, using lignin, has been proposed and developed. The analysis of the results indicates that the intermediates produced from lignin were responsible for enhancement in coal depolymerization rate, however, the intermediates are short-lived as compared to the time needed for a significant coal conversion yield. Coal depolymerization rate was found to be a function of time; compared to processing coal alone, it doubled upon reacting coal with lignin at 375{degree}C and after 67 minutes from the beginning of the experiment. Overall mass recoveries of 95--98% of the total mass charged to the reactor were obtained. A careful statistical analysis of the data shows that coal depolymerization yield is enhanced by 11.9% due to the lignin addition. The liquids obtained were examined for their elemental composition, and molecular weight determination by size exclusion chromatography. The stability of liquid products was characterized by determining their solubility in pentane and benzene, and by evaluating the molecular weight.

  5. Fine particle clay catalysts for coal liquefaction. Quarterly technical progress report, May 8, 1993--August 8, 1993

    SciTech Connect

    Olson, E.S.

    1995-10-01

    High hydrocracking and liquefaction activity can be achieved with 10 wt.% of sulfided clay-supported iron catalysts. Further tests and demonstrations of this activity were required. Iron hydroxyoxide was generated on acid-treated montmorillonite. The new batch of catalyst exhibited high hydrocracking activity, Three hour tests with the solubilized intermediate from low-severity treatment of Wyodak coal (LSW) gave a high conversion (45%) of the heptane-insoluble LSW intermediate to heptane-soluble products. An investigation of new methods for the production of catalysts from tetralin-soluble iron oxometallates and the determination of their catalytic activities was continued in this quarter. Iron oxotitanate and iron oxoaluminate gave very high conversions of LSW to heptane solubles (61% and 54%, respectively). The high yields of heptane soluble products obtained with these catalysts offers a potential for use in liquefaction stages with solubilized coal, or at least serve as a model for producing active catalysts via mixed metal oxides. Methods for successfully testing dispersed iron catalysts with the low-severity intermediate were also devised. Catalyst recovered from the dispersed iron hydroxyoxide-catalyzed reaction of ion-exchanged Wyodak gave a high conversion (47%) of LSW to heptane solubles.

  6. Dynamics of Disorder-Order Transitions in Hard Sphere Colloidal Dispersions in micro-g

    NASA Technical Reports Server (NTRS)

    Zhu, J. X.; Li, M.; Phan, S. E.; Russel, W. B.; Chaikin, Paul M.; Rogers, Rick; Meyers, W.

    1996-01-01

    We performed a series of experiments on 0.518 millimeter PMMA spheres suspended in an index matching mixture of decalin and tetralin the microgravity environment provided by the Shuttle Columbia on mission STS-73. The samples ranged in concentration from 0.49 to 0.62. volume fraction (phi) of spheres, which covers the range in which liquid, coexistence, solid and glass phases are expected from Earth bound experiments. Light scattering was used to probe the static structure, and the particle dynamics. Digital and 35 mm photos provided information on the morphology of the crystals. In general, the crystallites grew considerably larger (roughly an order of magnitude larger) than the same samples with identical treatment in 1 g. The dynamic light scattering shows the typical short time diffusion and long time caging effects found in 1 g. The surprises that were encountered in microgravity include the preponderance of random hexagonal close packed (RHCP) structures and the complete absence of the expected face centered cubic (FCC) structure, existence of large dendritic crystals floating in the coexistence samples (where liquid and solid phases coexist) and the rapid crystallization of samples which exist only in glass phase under the influence of one g. These results suggest that colloidal crystal growth is profoundly effected by gravity in yet unrecognized ways. We suspect that the RCHP structure is related to the nonequilibrium growth that is evident from the presence of dendrites. An analysis of the dendritic growth instabilities is presented within the framework of the Ackerson-Schatzel equation.

  7. Molecular characterization of effluent organic matter identified by ultrahigh resolution mass spectrometry.

    PubMed

    Gonsior, Michael; Zwartjes, Matthew; Cooper, William J; Song, Weihua; Ishida, Kenneth P; Tseng, Linda Y; Jeung, Matthew K; Rosso, Diego; Hertkorn, Norbert; Schmitt-Kopplin, Philippe

    2011-04-01

    Effluent dissolved organic matter (EfOM) collected from the secondary-treated wastewater of the Orange County Sanitation District (OCSD) located in Fountain Valley, California, USA was compared to natural organic matter collected from the Suwannee River (SRNOM), Florida using ultrahigh resolution electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR-MS). Furthermore, the two different treatment processes at OCSD, activated sludge and trickling filter, were separately investigated. The blend of these two effluents was further evaluated after it had passed through the microfiltration process of the Advanced Water Purification Facility (AWPF) at Orange County Water District (OCWD). EfOM contained 872 different m/z peaks that were unambiguously assigned to exact molecular formulae containing a single sulfur atom and carbon, hydrogen and oxygen atoms (CHOS formulae). In contrast, the SRNOM sample only contained 152 CHOS formulae. The trend in CHO molecular compositions was opposite with 2500 CHO formulae assigned for SRNOM but only about 1000 for EfOM. The CHOS-derived mass peaks with highest abundances in EfOM could be attributed to surfactants such as linear alkyl benzene sulfonates (LAS), their co-products dialkyl tetralin sulfonates (DATS) and their biodegraded metabolites such as sulfophenyl carboxylic acids (SPC). The differences between the treatments were found minor with greater differences between sampling dates than treatment methods used.

  8. Chemistry of fuel deposits and sediments and their predursors

    NASA Technical Reports Server (NTRS)

    Mayo, F. R.; Lan, B. Y.; Buttrill, S. E., Jr.; St.john, G. A.

    1984-01-01

    The mechanism of solid deposit formation on hot engine parts from turbine fuels is investigated. Deposit formation is associated with oxidation of the hydrocarbon fuel. Therefore, oxidation rates and soluble gum formation were measured for several jet turbine fuels and pure hydrocarbon mixtures. Experiments were performed at 130 C using thermal initiation and at 100 C using ditertiary butyl peroxide as a chemical initiator. Correlation of the data shows that the ratio of rate of oxidation to rate of gum formation for a single fuel is not much affected by experimental conditions, even though there are differences in the abilities of different hydrocarbons to initiate and continue the oxidation. This indicates a close association of gum formation with the oxidation process. Oxidations of n-dodecane, tetralin and the more unstable jet fuels are autocatalytic, while those of 2-ethylnaphthalene and a stable jet fuel are self-retarding. However, the ratio of oxidation rate to gum formation rate appear to be nearly constant for each substrate. The effect of oxygen pressure on gum and oxidation formation was also studied. Dependence of gum formation on the concentration of initiator at 100 C is discussed and problems for future study are suggested.

  9. Control of catalytic hydrotreating selectivity with ammonia

    SciTech Connect

    Satterfield, C.N.; Lee, Chung M.

    1990-01-01

    It was discovered that presence of low concentration of ammonia greatly reduces rate of hydrogenation of an aromatic compound (propylbenzene) on an industrial NiMo/Al[sub 2]O[sub 3] catalyst while it has only a mild inhibiting effect on hydrodenitrogenation (of quinoline). This suggests a way of industrial by reaction conditions of minimizing undesired aromatic hydrogenation during catalytic hydrodenitrogenation Coal liquids contain substantial amounts of a base fraction that consists of hydroxy pyridines, hydroxy indoles and/or hydroxy anilines. No information has been published on the HDN-HDO hydrotreating reactions of a compound in which a hydroxyl (phenolic) group is attached to a heterocyclic N compound. Thus the question has been raised of the extent to which quinoline HDN may or may not reflect the behaviour of such compounds. We have therefore performed a limited study with 8-hydroxy quinoline dissolved in tetralin utilizing a NiMo/Al[sub 2]O[sub 3] catalyst in a packed bed reactor operating at 360 and 385 and 6.9 MPa. We find that the N-heterocyclic ring is hydrogenated first to form an equilibrium mixture with a reaction intermediate identified as 8-OH-1,2,3,4 tetrahydroquinoline. Oxygen is then removed to form the same reaction intermediates we have observed from quinoline alone, but in somewhat different ratios. Therefore, with hydroxy-N-heterocyclic compounds, the OH group will likely be removed rapidly at the beginning.

  10. Control of catalytic hydrotreating selectivity with ammonia. [Quarterly] report

    SciTech Connect

    Satterfield, C.N.; Lee, Chung M.

    1990-12-31

    It was discovered that presence of low concentration of ammonia greatly reduces rate of hydrogenation of an aromatic compound (propylbenzene) on an industrial NiMo/Al{sub 2}O{sub 3} catalyst while it has only a mild inhibiting effect on hydrodenitrogenation (of quinoline). This suggests a way of industrial by reaction conditions of minimizing undesired aromatic hydrogenation during catalytic hydrodenitrogenation Coal liquids contain substantial amounts of a base fraction that consists of hydroxy pyridines, hydroxy indoles and/or hydroxy anilines. No information has been published on the HDN-HDO hydrotreating reactions of a compound in which a hydroxyl (phenolic) group is attached to a heterocyclic N compound. Thus the question has been raised of the extent to which quinoline HDN may or may not reflect the behaviour of such compounds. We have therefore performed a limited study with 8-hydroxy quinoline dissolved in tetralin utilizing a NiMo/Al{sub 2}O{sub 3} catalyst in a packed bed reactor operating at 360 and 385 and 6.9 MPa. We find that the N-heterocyclic ring is hydrogenated first to form an equilibrium mixture with a reaction intermediate identified as 8-OH-1,2,3,4 tetrahydroquinoline. Oxygen is then removed to form the same reaction intermediates we have observed from quinoline alone, but in somewhat different ratios. Therefore, with hydroxy-N-heterocyclic compounds, the OH group will likely be removed rapidly at the beginning.

  11. Tailoring hydrocarbon streams for asphaltene removal

    SciTech Connect

    Del Bianco, A.; Stroppa, F.; Bertero, L.

    1995-11-01

    Oilfield production is often hindered by asphaltene precipitation which tends to fill the pores of the reservoir rocks and plug the wellbore tubing as well as the other auxiliary equipment used during crude oil recovery. Several remedies to remove these deposits have been proposed and patented but the injection of aromatic solvents such as toluene and light petroleum distillates is normally preferred. Previous studies with a number of pure aromatic hydrocarbons have shown that the solvent capacity of these molecules may be very different and that the degree of condensation plays an important role. In this regard, tetralins and naphthalenes are superior to alkylbenzenes. However, because the use of pure compounds is not economically feasible, the authors examined various industrial streams and the authors correlated their chemical composition to the solvent capacity. This work allowed the identification of the pseudo-components whose relative concentration is crucial for evaluating the solvent performances. Based on these data, the authors were able to find new products with ideal characteristics. The efficiency of one of these products was confirmed by the analysis of the data obtained when using this new solvent to remove asphaltene in damaged wells of an Italian field.

  12. Part 1. The effect of microwave receptors on the liquefaction of Turkish coals by microwave energy in a hydrogen donor solvent

    SciTech Connect

    Emine Yagmur; Taner Togrul

    2005-12-01

    The effects of microwave receptors to coal (receptor/coal) ratio and the period of heating by microwave energy on the solubilization of Turkish coals (Tuncbilek, Mugla-Yatagan, Beypazari lignites, and Zonguldak bituminous coal) in tetralin have been investigated. V{sub 2}O{sub 5} and TiO{sub 2} were used as microwave receptors. The changes of liquid product yield indicated that it depended significantly on the type and amount of receptor and the type of coal. A significant increase in the lignite conversions to oil fractions was observed by the addition of the V{sub 2}O{sub 5} receptor. The use of TiO{sub 2} receptor decreased the yield of THF soluble coal products. However, both V{sub 2}O{sub 5} and TiO{sub 2} receptors decreased the yield of preasphaltene (PAS) and asphaltene (AS) due to their catalytic effect on the coal liquefaction. 15 refs., 9 figs., 1 tab.

  13. Asphaltene Adsorption onto Self-Assembled Monolayers of Alkyltrichlorosilanes of Varying Chain Length

    SciTech Connect

    Turgman-Cohen, S.; Fischer, D; Kilpatrick, P; Genzer, J

    2009-01-01

    The adsorption of asphaltenes onto flat silica surfaces modified with self-assembled monolayers (SAMs) of alkyltrichlorosilanes of varying thickness due to a variable number of carbon atoms (N{sub C}) has been studied by means of contact angle measurements, spectroscopic ellipsometry, and near-edge X-ray absorption fine structure spectroscopy. The extent of asphaltene adsorption was found to depend primarily on the ability of the SAM layer to shield the underlying silicon substrate from interacting with the asphaltenes present in solution. Specifically, asphaltene adsorption decreased with an increase in NC and/or an increase in SAM grafting density, {sigma}{sub SAM}, (i.e., number of SAM molecules per unit area). The effect of the solvent quality on the extent of asphaltene adsorption was gauged by adsorbing asphaltenes from toluene, 1-methylnaphthalene, tetralin, decalin, and toluene-heptanes mixtures. The extent of asphaltene adsorption was found to increase proportionally with a decrease in the Hildebrand solubility parameter of the solvent.

  14. Mechanisms for selective agglomeration of coals

    SciTech Connect

    Wheelock, T.D.; Drzymala, J.; Allen, R.W.; Hu, Y.-C.; Tyson, D.; Xiaoping, Qiu; Lessa, A.

    1989-05-01

    Work continued on the basic mechanisms which underlie various processes for beneficiating aqueous suspensions of coal by selective agglomeration with oil. A new method was demonstrated for characterizing the agglomerability of coal suspensions. This method utilizes a photometric dispersion analyzer to monitor changes in the turbidity of a particle suspension as increasing amounts of oil are added to the suspension in a batch agglomeration test. Agglomeration of the particles leads to a marked decrease in the turbidity of the suspension. Another experimental technique was also demonstrated for characterizing oil agglomeration. This technique involves measuring the rate of growth of agglomerates in a continuous flow system operating under stead-state conditions. The data are analyzed by means of a population balance. The results of a preliminary set of experiments in which Indiana V seam coal was agglomerated with tetralin seemed to fit a particular growth model very well. Equipment was also constructed for studying the kinetics of agglomeration in a batch process. While earlier work showed that quebracho (a commercially available dispersant) is a strong agglomeration depressant for pyrite, recent experiments with mixtures of Upper Freeport coal and mineral pyrite showed that quebracho does not appear to be sufficiently selective. Further consideration was given to the separation of mixtures of coal and pyrite agglomeration with heptane. 2 refs., 17 figs., 1 tab.

  15. Genetic dissection of independent and cooperative transcriptional activation by the LysR-type activator ThnR at close divergent promoters.

    PubMed

    Rivas-Marín, Elena; Floriano, Belén; Santero, Eduardo

    2016-04-18

    Regulation of tetralin biodegradation operons is one of the examples of unconventional LysR-type mediated transcriptional regulation. ThnR activates transcription from two divergent and closely located promoters PB and PC. Although ThnR activates each promoter independently, transcription from each one increases when both promoters are together. Mutational analysis of the intergenic region shows that cooperative transcription is achieved through formation of a ThnR complex when bound to its respective sites at each promoter, via formation of a DNA loop. Mutations also defined ThnR contact sites that are important for independent transcriptional activation at each promoter. A mutation at the PB promoter region, which abolishes its independent transcription, does not affect at all PB transcription in the presence of the divergent promoter PC, thus indicating that the complex formed via DNA loop can compensate for the deficiencies in the correct protein-DNA interaction at one of the promoters. Combination of mutations in both promoters identifies a region at PC that is not important for its independent transcription but it is essential for cooperative transcription from both promoters. This work provides new insights into the diversity and complexity of activation mechanisms used by the most abundant type of bacterial transcriptional regulators.

  16. Role of the hydrogen-donor solvent in coal hydroliquefaction. Progress report, September 1, 1979-November 30, 1980

    SciTech Connect

    Beishline, R.R.

    1980-07-25

    The principal disproportionation products of 1,2-dihydronaphthalene (1,2-DHN) are naphthalene (Nap) and tetralin (Tet). Dimers of 1,2-DHN constitute 17% and 5% of the respective liquid phase (285 to 315/sup 0/C) and gas phase (385 to 410/sup 0/C) products. The Nap:Tet ratio is one in the presence of solvents, but is > 1 and < 2 in their absence. Gas phase reaction kinetics indicate that 1,2-DHN disappears by simultaneous first and second order reactions. These results are consistent with a concerted second order disappearance of 1,2-DHN to produce equal amounts of Nap and Tet, accompanied by either carbonium ion or free radical side reactions that produce more Nap than Tet, together with 1,2-DHN dimers. Preliminary evaluation of the liquid phase kinetics suggest they follow a similar pattern. The structures of the dimers should reveal whether they were formed by a carbonium ion or free radical mechanism. Isolation of the dimers will be attempted by preparative GC (PGC) followed by TLC to remove thermal decomposition products formed during PGC. Exploratory results suggest that heating 1,2-DHN (300/sup 0/C) in the presence of tetraphenylethane, which dissociates into diphenylmethyl radicals, may constitute a model for the free radical conversion of 1,2-DHN into Nap during coal hydroliquefaction. Further studies of this system will be conducted.

  17. HIGH TEMPERATURE HIGH PRESSURE THERMODYNAMIC MEASUREMENTS FOR COAL MODEL COMPOUNDS

    SciTech Connect

    Vinayak N. Kabadi

    2000-05-01

    The Vapor Liquid Equilibrium measurement setup of this work was first established several years ago. It is a flow type high temperature high pressure apparatus which was designed to operate below 500 C temperature and 2000 psia pressure. Compared with the static method, this method has three major advantages: the first is that large quantity of sample can be obtained from the system without disturbing the equilibrium state which was established before; the second is that the residence time of the sample in the equilibrium cell is greatly reduced, thus decomposition or contamination of the sample can be effectively prevented; the third is that the flow system allows the sample to degas as it heats up since any non condensable gas will exit in the vapor stream, accumulate in the vapor condenser, and not be recirculated. The first few runs were made with Quinoline-Tetralin system, the results were fairly in agreement with the literature data . The former graduate student Amad used the same apparatus acquired the Benzene-Ethylbenzene system VLE data. This work used basically the same setup (several modifications had been made) to get the VLE data of Ethylbenzene-Quinoline system.

  18. MAINTENANCE OF THE COAL SAMPLE BANK AND DATABASE

    SciTech Connect

    Alan W. Scaroni; David C. Glick

    1998-08-01

    This project provides coal samples and accompanying analytical data for research by DOE contractors and others. All 56 samples have been purged with argon before storage, and the 33 samples in the DECS series are heat-sealed in foil laminate bags and stored under refrigeration. Eleven DECS samples have been collected under the current contract. Basic characterization, standardized liquefaction analyses and organic geochemical analyses have been completed. Distribution of samples and data is continuing, with processing of samples being performed as needed. Nineteen samples, 90 data printouts, and individual data items from 416 samples were distributed during the quarter. Trends and relationships observed in liquefaction and organic geochemical analyses performed under the contract are summarized in this report. Liquefaction results using tetralin were similar to those using 1-methylnaphthalene under the same run conditions. Properties of individual coals, such as maceral composition and corresponding organic chemical components, were important in explaining liquefaction behavior. NMR and py/gc/ms results illustrated trends based on coal rank, and revealed outliers which might be of special interest, for example low-phenolic coals which limit retrogressive reactions and permit greater liquefaction conversion.

  19. Measurement of the linear viscoelastic behavior of antimisting kerosene

    NASA Technical Reports Server (NTRS)

    Ferry, J. D.

    1983-01-01

    Measurements of dynamic viscoelastic properties in very small oscillating shear deformations was made on solutions of a jet fuel, Jet A, containing an antimisting polymeric additive, FM-9. A few measurements were also made on solutions of FM-9 in a mixed solvent of mineral oil, Tetralin, and 0-terphenyl. Two samples of FM-9 had approximate number-average molecular weights of 12,000,000 and 8,100,000 as deduced from analysis of the measurements. The ranges of variables were 2.42 to 4.03 g/1 in concentration (0.3 to 0.5% by weight), 1 to 35 in temperature, 1.3 to 9.4 cp in solvent viscosity, and 103 to 6100 Hz in frequency. Measurements in the Jet A solvent were made both with and without a modifying carrier. The results were compared with the Zimm theory and the viscoelastic behavior was found to resemble rather closely that of ordinary non-polar polymers in theta solvents. The relation of the results to the antithixotropic behavior of such solutions a high shear rates is discussed in terms of intramolecular and intermolecular interactions.

  20. Far infrared (terahertz) spectroscopy of a series of polycyclic aromatic hydrocarbons and application to structure interpretation of asphaltenes and related compounds

    NASA Astrophysics Data System (ADS)

    Cataldo, Franco; Angelini, Giancarlo; García-Hernández, D. A.; Manchado, Arturo

    2013-07-01

    A series of 33 different polycyclic aromatic hydrocarbons (PAHs) were studied by far infrared spectroscopy (terahertz spectroscopy) in the spectral range comprised between 600 and 50 cm-1. In addition to common PAHs like naphthalene, anthracene, phenanthrene, fluoranthene, picene, pyrene, benzo[α]pyrene, and perylene, also quite unusual PAHs were studied like tetracene, pentacene, acenaphtene, acenaphtylene, triphenylene, and decacyclene. A series of alkylated naphthalenes and anthracenes were studied as well as methypyrene. Partially or totally hydrogenated PAHs were also object of the present investigation, ranging from tetrahydronaphthalene (tetralin) to decahydronaphthalene (decalin), 9,10-dihydroanthracene, 9,10-dihydrophenanthrene, hexahydropyrene, and dodecahydrotriphenylene. Finally, the large and quite rare PAHs coronene, quaterrylene, hexabenzocoronene, and dicoronylene were studied by far infrared spectroscopy. The resulting reference spectra were used in the interpretation of the chemical structure of asphaltenes (as extracted from a heavy petroleum fraction and from bitumen), the chemical structures of other petroleum fractions known as DAE (distillate aromatic extract) and RAE (residual aromatic extract), and a possible interpretation of components of the chemical structure of anthracite coal. Asphaltenes, heavy petroleum fractions, and coal were proposed as model compounds for the interpretation of the emission spectra of certain proto-planetary nebulae (PPNe) with a good matching in the mid infrared between the band pattern of the PPNe emission spectra and the spectra of these oil fractions or coal. Although this study was finalized in an astrochemical context, it may find application also in the petroleum and coal chemistry.

  1. THE IMPACT OF TRACE ADDITIVES ON THE APPARENT SOLUBILITY OF HYDROGEN IN HEAVY OIL AND RELATED FEEDSTOCKS AT LOW AND HIGH TEMPERATURES

    SciTech Connect

    Jalal Abedi

    2002-09-01

    A systematic investigation was conducted to provide an accurate determination of hydrogen solubility in liquid media in temperatures in the range of 25-250 C and pressures in the range of 0.5-8 MPa. Results were obtained by an indirect gas solubility measurement method. The method was intended for use with high-resolution camera. The hydrogen solubility measurements were indirect and were based on pressure changes at constant temperature and measured volumes. Since the volume of the view cell was fixed the volume available for the vapor phase could be determined by measuring the location of the liquid-vapor interface. The interface was located to within the height of one pixel using high-resolution camera, which added {+-} 0.4 ml to the uncertainty of the vapor volume. Liquid-liquid interface locations were measured with equal precision. The accuracy of the method was illustrated through hydrogen solubility measurements in hexadecane and tetralin, which were in close agreement with the values available in the literature. Hydrogen solubilities in Athabasca bitumen vacuum bottoms (ABVB) were reported over a broad range of temperatures (80-250 C) and pressures (0.5-8 MPa).

  2. Far infrared (terahertz) spectroscopy of a series of polycyclic aromatic hydrocarbons and application to structure interpretation of asphaltenes and related compounds.

    PubMed

    Cataldo, Franco; Angelini, Giancarlo; García-Hernández, D Aníbal; Manchado, Arturo

    2013-07-01

    A series of 33 different polycyclic aromatic hydrocarbons (PAHs) were studied by far infrared spectroscopy (terahertz spectroscopy) in the spectral range comprised between 600 and 50 cm(-1). In addition to common PAHs like naphthalene, anthracene, phenanthrene, fluoranthene, picene, pyrene, benzo[α]pyrene, and perylene, also quite unusual PAHs were studied like tetracene, pentacene, acenaphtene, acenaphtylene, triphenylene, and decacyclene. A series of alkylated naphthalenes and anthracenes were studied as well as methypyrene. Partially or totally hydrogenated PAHs were also object of the present investigation, ranging from tetrahydronaphthalene (tetralin) to decahydronaphthalene (decalin), 9,10-dihydroanthracene, 9,10-dihydrophenanthrene, hexahydropyrene, and dodecahydrotriphenylene. Finally, the large and quite rare PAHs coronene, quaterrylene, hexabenzocoronene, and dicoronylene were studied by far infrared spectroscopy. The resulting reference spectra were used in the interpretation of the chemical structure of asphaltenes (as extracted from a heavy petroleum fraction and from bitumen), the chemical structures of other petroleum fractions known as DAE (distillate aromatic extract) and RAE (residual aromatic extract), and a possible interpretation of components of the chemical structure of anthracite coal. Asphaltenes, heavy petroleum fractions, and coal were proposed as model compounds for the interpretation of the emission spectra of certain proto-planetary nebulae (PPNe) with a good matching in the mid infrared between the band pattern of the PPNe emission spectra and the spectra of these oil fractions or coal. Although this study was finalized in an astrochemical context, it may find application also in the petroleum and coal chemistry.

  3. Asphaltene adsorption onto self-assembled monolayers of alkyltrichlorosilanes of varying chain length.

    PubMed

    Turgman-Cohen, Salomon; Fischer, Daniel A; Kilpatrick, Peter K; Genzer, Jan

    2009-06-01

    The adsorption of asphaltenes onto flat silica surfaces modified with self-assembled monolayers (SAMs) of alkyltrichlorosilanes of varying thickness due to a variable number of carbon atoms (N(C)) has been studied by means of contact angle measurements, spectroscopic ellipsometry, and near-edge X-ray absorption fine structure spectroscopy. The extent of asphaltene adsorption was found to depend primarily on the ability of the SAM layer to shield the underlying silicon substrate from interacting with the asphaltenes present in solution. Specifically, asphaltene adsorption decreased with an increase in N(C) and/or an increase in SAM grafting density, sigma(SAM), (i.e., number of SAM molecules per unit area). The effect of the solvent quality on the extent of asphaltene adsorption was gauged by adsorbing asphaltenes from toluene, 1-methylnaphthalene, tetralin, decalin, and toluene-heptanes mixtures. The extent of asphaltene adsorption was found to increase proportionally with a decrease in the Hildebrand solubility parameter of the solvent.

  4. Kinetic modeling of direct liquefaction of wyodak coal catalyzed by sulfated iron oxides

    SciTech Connect

    Prodhan, V.R.; Holder, G.D.; Wonder, I.; Tierney, J.W.

    1992-08-01

    This paper describes the kinetics of the direct liquefaction of Wyodak coal using tetralin and 1000 psig (cold) H[sub 2] were experimentally measured and mathematically modeled. Experiments were carried out in a 27-cm[sup 3] horizontally shaken autoclave microreactor at 648-698 K for reaction times of 5--120 min. Some experiments were carried out at lower temperatures to determine if the model would be accurate at such conditions. Three catalyst combinations were used, Mo/Fe[sub 2]O[sub 3]/SO[sub 4], Fe[sub 2]O[sub 3]/SO[sub 4], and Fe[sub 2]O[sub 3], each with elemental sulfur. Four reaction pathways were considered: coal to asphaltenes, coal to gas, coal to oils, and asphaltenes to oils. In each pathway (except for the conversion of coal to gas), parallel thermal and catalytic reactions were included. The conversion of coal to asphaltenes was found to be primarily thermal and conversion of asphaltenes to oils was primarily catalytic, while conversion of coal to oils had significant thermal and catalytic contributions. The frequency factor and activation energy of each significant rate constant were estimated by correlating data for all temperatures (16 parameters).

  5. Central ventilatory and cardiovascular actions of serotonin in trout.

    PubMed

    Kermorgant, Marc; Lancien, Frédéric; Mimassi, Nagi; Le Mével, Jean-Claude

    2014-02-01

    This study was undertaken to investigate the central actions of 5-HT on ventilatory and cardiovascular variables in the unanesthetized trout. Compared to vehicle, intracerebroventricular injection (ICV) of 5-HT elevated the total ventilation. This elevation was due to its stimulatory action on ventilatory amplitude. Moreover, 5-HT produced a dose-dependent increase in mean dorsal aortic blood pressure (PDA) without change in heart rate (fH). Methysergide, a 5-HT1/5-HT2 receptor antagonist, reduced the hyperventilatory and hypertensive actions of 5-HT. 8-OH-2-(di-n-propylamino) tetralin, a 5-HT1A receptor agonist, increased PDA while α-methyl-5-HT, a 5-HT2 receptor agonist, elevated all ventilatory variables and increased PDA without changing fH. Intra-arterial injection of 5-HT was without effect on ventilation, but 5-HT initially produced hypotension followed by hypertension. These changes were accompanied by tachycardia. It remains to be determined whether endogenous 5-HT within the brain of trout may act as a potent neuroregulator causing stimulatory effects on cardio-ventilatory functions. In the periphery, 5-HT may act as local modulator involved in vasoregulatory mechanisms.

  6. The effect of 3,4-methylenedioxymethamphetamine ('Ecstasy') on serotonergic regulation of the mammalian circadian clock mechanism in rats: the role of dopamine and hyperthermia.

    PubMed

    Dafters, Richard I; Biello, Stephany M

    2003-10-23

    The recreational drug 3,4-methylenedioxymethamphetamine (MDMA) is known to be a neurotoxin for serotonergic axons ascending from the raphe nucleus including those which terminate on neurons of the suprachiasmatic nuclei (SCN) of the hypothalamus, the putative mammalian circadian clock. Since dopamine release has been implicated in the serotonergic neurotoxicity, we examined the effects of the dopamine synthesis inhibitor alpha-methyl-p-tyrosine (AMPT) and the D2 receptor antagonist haloperidol (HAL) on the long-term effect of MDMA on serotonergic regulation of the SCN neuronal firing rhythm. Co-administration of AMPT or HAL with MDMA eliminated the acute hyperthermic response but had no effect on the MDMA-induced phase shift in the firing rhythm of SCN neurons to the selective 5-HT1A receptor agonist, 8-hydroxy-2-(dipropylamino)-tetralin. It is concluded that neither dopamine metabolism nor hyperthermia account for the altered serotonergic function in the SCN produced by MDMA. Toxic free radical production following MDMA metabolism may be responsible.

  7. HIGH TEMPERATURE HIGH PRESSURE THERMODYNAMIC MEASUREMENTS FOR COAL MODEL COMPOUNDS

    SciTech Connect

    Vinayak N. Kabadi

    2000-05-01

    The flow VLE apparatus designed and built for a previous project was upgraded and recalibrated for data measurements for this project. The modifications include better and more accurate sampling technique, addition of a digital recorder to monitor temperature and pressure inside the VLE cell, and a new technique for remote sensing of the liquid level in the cell. VLE data measurements for three binary systems, tetralin-quinoline, benzene--ethylbenzene and ethylbenzene--quinoline, have been completed. The temperature ranges of data measurements were 325 C to 370 C for the first system, 180 C to 300 C for the second system, and 225 C to 380 C for the third system. The smoothed data were found to be fairly well behaved when subjected to thermodynamic consistency tests. SETARAM C-80 calorimeter was used for incremental enthalpy and heat capacity measurements for benzene--ethylbenzene binary liquid mixtures. Data were measured from 30 C to 285 C for liquid mixtures covering the entire composition range. An apparatus has been designed for simultaneous measurement of excess volume and incremental enthalpy of liquid mixtures at temperatures from 30 C to 300 C. The apparatus has been tested and is ready for data measurements. A flow apparatus for measurement of heat of mixing of liquid mixtures at high temperatures has also been designed, and is currently being tested and calibrated.

  8. Fundamentals of coal depolymerization under hydroliquefaction conditions: kinetic and structural analyses of a bituminous (Powhatan No. 5) coal and its liquefaction products. Quarterly report, July 1-September 30, 1981

    SciTech Connect

    Petrakis, L.; Grandy, D.W.; Gavalas, G.; Allen, D.T.; Oka, M.; Maciel, G.; Sullivan, M.

    1981-09-01

    This is one of the three volumes that constitute the final report for the title project. The objectives of the project included: (a) the use of /sup 13/C solid state NMR to assess the structural features of a given coal (Powhatan No. 5) and how its structure might change upon hydroliquefaction; (b) the petrographic assessment of the maceral make-up of the coal and the petrographic changes upon hydroliquefaction; (c) a better definition of the molecular profile of the products so that eventually reaction pathways of coal molecules upon hydroliquefaction might be delineated. This volume contains material that addresses these objectives. Under a subcontract to Colorado State University, solid state /sup 13/C NMR was used for a very detailed investigation of Powhatan No. 5 coal and to study certain macerals as well as the structural features of the coal under different hydroliquefaction conditions. For some of the macerals, important structural features are obtained other than the usual aromatic/nonaromatic carbon ratio. The petrographic changes under different hydroliquefaction conditions are shown. Some of the work entailed the development and utilization of methodology for the definition of the chemical structures of coal liquids. In addition, the pyrolytic behavior of a model system (tetralin) was pursued using thermochemical techniques. The overall implication and pertinence of these aspects of the work to the fundamentals of the depolymerization of Powhatan No. 5 coal are presented in the Executive Summary for this project (Report FE-14940-8).

  9. Towards the specification of consecutive steps in macromolecular lignin assembly

    NASA Technical Reports Server (NTRS)

    Nose, M.; Bernards, M. A.; Furlan, M.; Zajicek, J.; Eberhardt, T. L.; Lewis, N. G.

    1995-01-01

    When Pinus taeda cell suspension cultures are exposed to 8% sucrose solution, the cells undergo significant intracellular disruption, irregular wall thickening/lignification with concomitant formation of an 'extracellular lignin precipitate. However, addition of potassium iodide (KI), an H202 scavenger, inhibits this lignification response, while the ability to synthesize the monolignols, p-coumaryl and coniferyl alcohols, is retained. Lignin synthesis (i.e. polymerization) is thus temporarily correlated with H202 generation, strongly implying a regulatory role for the latter. Time course analyses of extracellular metabolites leading up to polymer formation reveal that coniferyl alcohol, but not p-coumaryl alcohol, undergoes substantial coupling reactions to give various lignans. Of these, the metabolites, dihydrodehydrodiconiferyl alcohol, shonanin (divanillyl tetrahydrofuran) and its apparent aryl tetralin derivative, cannot be explained simply on the basis of phenolic coupling. It is proposed that these moieties are the precursors of so-called reduced substructures in the lignin macromolecule. This adds a new perspective to the lignin assembly mechanism.

  10. Effect of coal liquefaction conditions on the composition of the product oil

    SciTech Connect

    Karaca, H.

    2006-12-15

    Two methods, catalyst physically mixing method (method I) and catalyst impregnation method (method II) were employed for Beypazari and Tuncbilek lignites liquefaction. Fe{sub 2}O{sub 3} and Mo(CO){sub 6} were used as the catalysts. Oils obtained at the end of the catalytic coal liquefaction were qualitatively analyzed by gas chromatography (GC). With solvent/coal ratio increase, compounds with straight chain and high molecular weight were formed. Likewise, as the reaction time and catalyst concentration were increased, the number and the intensity of the compounds in the oils increased partially. Due to the increase in the reaction time, temperature and catalyst concentration, the oils were enriched in straight chain alkanes and aromatic polycyclic compounds. However, alkanes with straight chain were reduced by the effect of pyrolysis at temperatures over 400{sup o}C. Retention times of the compounds obtained by method II were higher than those of the compounds obtained by method I. Respectively, the compounds in the oils obtained by method II were found to have been composed by high quantities of high molecular straight chain alkanes and aromatic polycyclic compounds. Our data gave us ground to presume that the oils from both lignites were composed by straight chain alkanes and aromatic polycyclic compounds (tetralin, naphthalene and their derivatives, phenols, xylenols, biphenyl, naphthols, etc.). The oil compositions were strongly influenced by the liquefaction conditions.

  11. Role of iron-based catalyst and hydrogen transfer in direct coal liquefaction

    SciTech Connect

    Xian Li; Shuxun Hu; Lijun Jin; Haoquan Hu

    2008-03-15

    The aim of this research is to understand the major function of iron-based catalysts on direct coal liquefaction (DCL). Pyrolysis and direct liquefaction of Shenhua bituminous coal were carried out to investigate the effect of three solvents (wash-oil from coal-tar, cycle-oil from coal liquefaction, and tetralin) in a N{sub 2} or a H{sub 2} atmosphere and with or without catalyst. The hydrogen content in the solvent and liquid product and the H{sub 2} consumption for every run were calculated to understand the hydrogen transfer approach in DCL. The results showed that the iron-based catalyst promotes the coal pyrolysis, and the dominating function of the catalyst in DCL is to promote the formation of activated hydrogen and to accelerate the secondary distribution of H in the reaction system including the gas, liquid, and solid phases. The major transfer approach of the activated hydrogen is from molecular hydrogen to solvent and then from solvent to coal, and the solvent takes on the role of a 'bridge' in the hydrogen transfer approach. 31 refs., 5 figs., 3 tabs.

  12. Additive effect of waste tire on the hydrogenolysis reaction of coal liquefaction residue

    SciTech Connect

    Motoyuki Sugano; Daigorou Onda; Kiyoshi Mashimo

    2006-12-15

    A numerous amount of waste tire is landfilled or dumped all over the world, which causes environmental problems, such as destruction of natural places and the risk of fires. On the other hand, the coal liquefaction residue (CLR) is produced in 30% yield through the process supporting unit (PSU) of the NEDOL coal liquefaction process. Therefore, the investigation on an effective method for utilization of waste tire and CLR is required. In this study, the simultaneous hydrogenolysis of CLR and pulverized waste tire was carried out by using tetralin. The yields in the simultaneous hydrogenolysis were compared with algebraic sum of the yields of the individual hydrogenolyses of waste tire alone and coal alone. In the simultaneous hydrogenolysis, the synergistic effects to upgrading, such as an increase in the yield of the oil constituent and a decrease in the yield of the asphaltene constituent, occurred because of the stabilization of asphaltenic radicals from CLR with aliphatic radicals from tire. The decrease in asphaltene yield in the simultaneous hydrogenolysis was pronounced with the increase in the tire:CLR ratio because the solvent effects of liquefied tire, such as stabilization of radicals, hydrogen shuttling, and heat transfer, were enhanced. Accordingly, it is estimated that the simultaneous hydrogenolysis of CLR and waste tire is an effective method for processing both materials. 15 refs., 3 figs., 2 tabs.

  13. Catalysis and co-catalysis of bond cleavages in coal and coal analogs. Final report, August 1, 1990--January 31, 1994

    SciTech Connect

    Miller, B.

    1994-05-01

    In work prior to the inception of this project, the authors observed that mixtures of phenolic materials and polyalkoxyaromatic molecules were appreciably more effective in catalyzing the decompositions of di-2-naphthyl ether and of di-1-naphthyl sulfide in tetralin solutions at 450{degrees}C than were the phenols by themselves, even though the polyalkoxyaromatic molecules, in the absence of phenolic co- catalysts, show essentially no catalytic activity. This was of appreciable interest in coal research because dinapthyl ether and dinapthyl sulfide have been employed as model compounds for coals in studies aimed at cleaving ether and sulfide bonds similar to those in coals. The authors proposed (R. K. Sharma, K. P. Raman, and B. Miller) that the mixed catalysts used in these studies catalyze cleavages of ether and sulfide bonds by means of a mechanism involving electron transfer from the polyalkoxyaromatics to the substrates, which are activated as electron acceptors by hydrogen bonding to phenols. Since phenols themselves are electron donors, they also proposed that the well known effects of phenols in catalyzing the conversion of coals are due to similar electron transfer mechanisms.

  14. Development of (S)-N6-(2-(4-(Isoquinolin-1-yl)piperazin-1-yl)ethyl)-N6-propyl-4,5,6,7-tetrahydrobenzo[d]-thiazole-2,6-diamine and its analogue as a D3 receptor preferring agonist: Potent in vivo activity in Parkinson’s disease animal models

    PubMed Central

    Ghosh, Balaram; Antonio, Tamara; Zhen, Juan; Kharkar, Prashant; Reith, Maarten E. A.; Dutta, Aloke K.

    2010-01-01

    Here we report structure-activity relationship study of a novel hybrid series of compounds where structural alteration of aromatic hydrophobic moieties connected to the piperazine ring and bioisosteric replacement of the aromatic tetralin moieties were carried out. Binding assays were carried out with HEK-293 cells expressing either D2 or D3 receptors with tritiated spiperone to evaluate inhibition constants (Ki). Functional activity of selected compounds in stimulating GTPγS binding was assessed with CHO cells expressing human D2 receptors and AtT-20 cells expressing human D3 receptors. SAR results identified compound (−)-24c (D-301) as one of the lead molecules with preferential agonist activity for D3 receptor (EC50 (GTPγS); D3 = 0.52 nM; D2/D3 (EC50): 223). Compounds (−)-24b and (−)-24c exhibited potent radical scavenging activity. The two lead compounds (−)-24b and (−)-24c exhibited high in vivo activity in two Parkinson’s disease (PD) animal models, reserpinized rat model and 6-OH-DA induced unilaterally lesioned rat model. Future studies will explore potential use of these compounds in the neuroprotective therapy for PD. PMID:20038106

  15. Identification of persistent anionic surfactant-derived chemicals in sewage effluent and groundwater

    USGS Publications Warehouse

    Field, Jennifer A.; Leenheer, Jerry A.; Thorn, Kevin A.; Barber, Larry B.; Rostad, Colleen; Macalady, Donald L.; Daniel, Stephen R.

    1992-01-01

    Preparative isolation and fractionation procedures coupled with spectrometric analyses were used to identify surfactant-derived contaminants in sewage effluent and sewage-contaminated groundwater from a site located on Cape Cod, Massachusetts. Anionic surfactants and their biodegradation intermediates were isolated from field samples by ion exchange and fractionated by solvent extraction and adsorption chromatography. Fractions were analyzed by 13C nuclear magnetic resonance spectrometry and gas chromatography-mass spectrometry. Carboxylated residues of alkylphenol polyethoxylate surfactants were detected in sewage effluent and contaminated groundwater. Linear alkylbenzenesulfonates (LAS) were identified in sewage effluent and groundwater. Groundwater LAS composition suggested preferential removal of select isomers and homologs due to processes of biodegradation and partitioning. Tetralin and indane sulfonates (DATS), alicyclic analogs of LAS, were also identified in field samples. Although DATS are a minor portion of LAS formulations, equivalent concentrations of LAS and DATS in groundwater suggested persistence of alicyclic contaminant structures over those of linear structure. Sulfophenyl-carboxylated (SPC) LAS biodegradation intermediates were determined in sewage effluent and groundwater. Homolog distributions suggested that SPC containing 3–10 alkyl-chain carbons persist during infiltration and groundwater transport. Surfactant-derived residues detected in well F300-50 groundwater have a minimum residence time in the range of 2.7–4.6 yr. LAS detected in groundwater at 500 m from infiltration has been stable over an estimated 50–500 half lives.

  16. Identification of persisten anionic surfactant-derived chemicals in sewage effluent and groundwater

    USGS Publications Warehouse

    Field, J.A.; Leenheer, J.A.; Thorn, K.A.; Barber, L.B.; Rostad, C.; Macalady, D.L.; Daniel, S.R.

    1992-01-01

    Preparative isolation and fractionation procedures coupled with spectrometric analyses were used to identify surfactant-derived contaminants in sewage effluent and sewage-contaminated groundwater from a site located on Cape Cod, Massachusetts. Anionic surfactants and their biodegradation intermediates were isolated from field samples by ion exchange and fractionated by solvent extraction and adsorption chromatography. Fractions were analyzed by 13C nuclear magnetic resonance spectrometry and gas chromatography-mass spectrometry. Carboxylated residues of alkylphenol polyethoxylate surfactants were detected in sewage effluent and contaminated groundwater. Linear alkylbenzenesulfonates (LAS) were identified in sewage effluent and groundwater. Groundwater LAS composition suggested preferential removal of select isomers and homologs due to processes of biodegradation and partitioning. Tetralin and indane sulfonates (DATS), alicyclic analogs of LAS, were also identified in field samples. Although DATS are a minor portion of LAS formulations, equivalent concentrations of LAS and DATS in groundwater suggested persistence of alicyclic contaminant structures over those of linear structure. Sulfophenyl-carboxylated (SPC) LAS biodegradation intermediates were determined in sewage effluent and groundwater. Homolog distributions suggested that SPC containing 3-10 alkyl-chain carbons persist during infiltration and groundwater transport. Surfactant-derived residues detected in well F300-50 groundwater have a minimum residence time in the range of 2.7-4.6 yr. LAS detected in groundwater at 500 m from infiltration has been stable over an estimated 50-500 half lives.

  17. Identification of drinking water contaminants in the course of a childhood cancer investigation in Toms River, New Jersey.

    PubMed

    Richardson, S D; Collette, T W; Price, P C; Genicola, F A; Jenks, J W; Thruston, A D; Ellington, J J

    1999-01-01

    Using a combination of gas chromatography/mass spectrometry (GC/MS) and gas chromatography/infrared spectroscopy (GC/IR) spectroscopic techniques, chemical contaminants and their hydrolysis products were identified in well water sampled in connection with a suspected childhood cancer cluster located in Dover Township, Ocean County, New Jersey. The drinking water contamination resulted from the leaching of industrial waste chemicals from drums that were disposed of at the site known as Reich Farm. Contaminants identified include dinitrile-tetralin compounds, known as 'trimers,' that are by-products of a polymerization process widely used by several polymer manufactures during the 1970s and 1980s (and still used today). Also identified were 'trimer' hydrolysis products, formed by the hydrolysis of their nitrile groups to amides. These industrial contaminants were not present in any of the mass or IR spectral library databases, and their identification required unconventional spectroscopic methods (including high resolution mass spectrometry, chemical ionization mass spectrometry, and IR spectroscopy), along with scientific reasoning and interpretation. It is currently not known whether these chemical contaminants are responsible for the childhood cancers observed in this area.

  18. Chemistry and morphology of coal liquefaction. Annual report, October 1, 1979-September 30, 1980

    SciTech Connect

    Heinemann, H.

    1980-09-01

    The present annual report summarizes quarterly reports and includes work performed during the last quarter of fiscal 1980. The first year of this project has just been completed and much of the time and effort has been concentrated on equipment building, assembling, testing, and on staffing. This, of course, has been more true in the areas of work with spectroscopic and high pressure equipment than in organic chemical reactions. More experimental results are therefore reported in the areas of hydrogen transfer mechanisms and catalysis and organo-metallic chemistry. A few of the significant results in these and other areas are the evidence for catalysis in hydrogen transfer from tetralin; a novel and possibly very important new synthesis of alkyl aromatics from benzene, carbon monoxide, and hydrogen; the study of coals in the transmission electron microscope identifying coal macerals, minerals and metals, and leading to the possibility of observing location of and catalytic influences on pyrolysis and hydrogenation at elevated temperatures; the finding that scales formed on deactivated cobalt-molybdena-alumina-hydrogenation catalysts contain not only metals from the liquid feedstocks, but also molybdenum sulfide which must derive from migration from the catalyst interior to and beyond the surface. Insights gained in mechanisms of pyrolysis, hydrogenation, hydrogen transfer, and indirect liquefaction of coal promise to lead to improving technology by defining problem areas and showing routes to by-pass problems.

  19. Low severity coal liquefaction promoted by cyclic olefins. Quarterly report, October--December 1993

    SciTech Connect

    Curtis, C.W.

    1993-12-31

    Acid pretreatment removes those alkaline metal and alkaline earth cations which inhibit coal reactivity and hydrogen transfer. Shams et al. (1992) found that through this pretreatment a large portion of the calcium present in coal was removed. Hydrochloric acid was used in that study, but sulfurous acid, if similar results are achieved, would be a much more suitable acid for processing. Another pretreatment method to remove these cations is one using ammonium acetate (Hengel and Walker, 1984). This study will evaluate the effect of combining these two principles, acid pretreatment of coal and rapid hydrogen transfer, for improving hydrogen transfer under low severity conditions. The acid pretreatment methods showed more success with low rank, subbituminous coals and lignite. Therefore, Wyodak subbituminous coal (WY) from the Argonne Premium Sample Bank and Black Thunder subbituminous coal (BT) from Amoco are being used and compared in this study. The cyclic olefin, 1,4,5,8-tetrahydronaphthalene (isotetralin, ISO) and its analogue, 1,2,3,4-tetrahydronaphthalene (tetralin, TET), will also be used and compared in this study. The efficacy of the two-ringed ISO can then be compared with the previously studied three-ringed HHA. Dr. James Hool, Professor of Industrial Engineering and an expert in statistics and experimental design, assisted in formulating the four-dimensional experimental matrix found in Figure 1. It is through this parametric analysis that the effect of each factor in this pretreatment and low severity liquefaction system will be determined.

  20. Low severity coal liquefaction promoted by cyclic olefins. Quarterly report, January--March 1996

    SciTech Connect

    Curtis, C.W.

    1996-05-01

    The goal of this research is to develop a methodology for analyzing the reactivity of cyclic olefins in situ in a high temperature and high pressure infrared cell. Cyclic olefins, such as 1,4,5,8-tetrahydronaphthalene (isotetralin) and 1,4,5,8,9, 10-hexahydroanthracene (HHA), are highly reactive donor compounds that readily donate their hydrogen to coal and model acceptors when heated to temperatures of 200 C and above. These donors are active donors in the low severity liquefaction of coal at 350 C as shown in the research performed in this project. The infrared studies are being performed in a high temperature infrared cell that was obtained from AABSPEC. Modifications to that cell have been made and have been reported in previous progress reports. Previous studies had shown that naphthalene was quite stable at temperatures up to 230 C, but a more definitive stability study was conducted to confirm this observation. Stability studies also confirmed the non-reactivity of decaline and tetralin at elevated temperatures up to 230 C. High temperature FTIR analysis of isotetralin showed that isotetralin reacted at temperatures of 100 C and higher to 230 C. This quarter, the reaction product spectrum was analyzed to determine the primary product.

  1. Steam reforming of liquid hydrocarbons over a nickel-alumina spinel catalyst

    NASA Astrophysics Data System (ADS)

    Fauteux-Lefebvre, Clémence; Abatzoglou, Nicolas; Blanchard, Jasmin; Gitzhofer, François

    Interest in steam reforming of liquid hydrocarbons is growing due to the necessity of developing reliable alternatives for their use in fuel cells. In particular, solid oxide fuel cells, which can operate with mixtures of H 2 and CO, are excellent candidates for being fed with liquid fuels coming from both fossil and renewable sources. Fossil-derived, synthetic diesel is an interesting option. In this work, an Al 2O 3-ZrO 2-supported nickel-alumina spinel was tested in a lab-scale isothermal packed-bed reactor as a catalyst of steam reforming of propane, hexadecane and tetralin as surrogates of constitutive families of all commercially available diesel fuels. The results show that the reaction reaches equilibrium at reaction severities lower than those reported in the literature. When operated at steam excess of 250%, carbon formation is not higher than expected by theoretical thermodynamic equilibrium calculations, and no significant catalyst deactivation is observed over the test durations. Scanning electron microscopy of the fresh and used catalyst surfaces shows no significant quantities of carbon.

  2. Novel process for depolymerization of coal to C{sub 2}-C{sub 4} hydrocarbons. Final report, 1 September 1989--31 August 1993

    SciTech Connect

    Wiser, W.H.; Oblad, A.G.

    1994-07-08

    A principal objective of this work was to study the conversion of coal to C{sub 2} {minus} C{sub 4} hydrocarbons in a two-stage reactor system. Coal was converted to liquids at 440{degrees}C in a stirred batch autoclave using tetralin as the hydrogen donor solvent. The liquids produced were separated from the unreacted coal and ash by filtration. The liquids were then fed into a second stage fixed bed reactor containing sulfided Ni-Mo/Al{sub 2}O{sub 3} and SiO{sub 2{minus}}Al{sub 2}O{sub 3} catalyst. The liquids were hydrocracked on the dual functional catalyst giving high yields of C{sub 2} {minus} C{sub 4}. hydrocarbons. The pressure was 1800 psi and the temperatures were in the range of 425 to 500{degrees}C. The kinetic parameters of the conversion of coal liquids to gases were determined. The activation energy was determined.

  3. Synthesis of acrylates. Quarterly report, 1996

    SciTech Connect

    1996-07-01

    Over the last quarter, Eastman has completed its experimental program on propionyl generation portion of the process. An improved olefin carbonylation process has been developed as the basis of the propionate synthesis portion of the project (Task 1). Bechtel has also completed a production cost estimate for the synthesis of propionic anhydride from ethylene, carbon monoxide, and recycled propionic acid based on the yields demonstrated for the Eastman carbonylation process. The results show a cost of $0.43/lb, which we judge to be competitive as a basis for MMA, which sells for about $0. 75/lb. RTI has tested (Task 2) over 71 acid-base catalysts for the condensation of propionic anhydride/acid with formaldehyde. Other catalysts are being tested to minimize the deactivation observed on these materials. These catalysts are more likely than the V-Si-P catalysts as potential candidates for a commercial process. RTI has also completed the assembly and operation of a HTHP slurry reactor system for demonstration of liquid phase synthesis (Task 3). NCSU has tested slurry fluids including decalin and tetralin for hydrothermal, oxidative, and reductive stability. The results of their effort will be directly applicable to bench-scale testing in the RTI HTHP slurry reactor.

  4. Thermodynamic and transport properties for polar coal mixtures. Technical progress report, October 1-December 31, 1985

    SciTech Connect

    Stiel, L.I.

    1985-01-01

    Additional measurements of the infinite dilution activity coefficient have been conducted for nonpolar and polar solutes in coal liquids. The temperature ranges considered were extended for several solutes with tetralin, including ethanol and n-propanol. Values of infinite dilution activity coefficients were also measured for m-cresol systems for temperatures from 50 to 80/sup 0/C. The results are presented in Table I for a number of solutes at 60/sup 0/C. It can be seen that the activity coefficients for polar solutes with m-cresol are less than 1.0, indicating strong molecular interactions for these systems. For n-hexane, carbon tetrachloride, and cyclohexane with m-cresol, the values of infinite dilution activity coefficient show only small dependences on temperature in the range of 50 to 80/sup 0/C. Measurements are also being obtained for non-polar and polar solutes in quinoline. Preliminary values for these systems at 60/sup 0/C are presented in Table I. An improved relationship for the latent heat of vaporization lambda of polar fluids is being developed which will aid in the establishment of accurate characterization parameters for coal liquids. 10 refs., 8 figs., 1 tab.

  5. Low severity coal liquefaction promoted by cyclic olefins. Quarterly report, January--March 1994

    SciTech Connect

    Curtis, C.W.

    1994-06-01

    Previous research has suggested that using a more effective hydrogen donor solvent in the low severity coal liquefaction reaction improves coal conversion. In order to understand the results of these methods, both independently and combined, a factorial experiment was designed. Pretreating coal with hydrochloric and sulfurous acid solutions in both water and methanol is compared with pretreating coal using only methanol and with no pretreatment. The effects of these pretreatments on coal liquefaction behavior are contrasted with the ammonium acetate pretreatment. Within each of these, individual reactions are performed with the hydroaromatic 1,2,3,4-tetrahydronaphthalene (tetralin, TET) and the cyclic olefin 1,4,5,8-tetrahydronaphthalene (isotetralin, ISO). The final aspect of the factorial experiment is the comparison of Wyodak subbituminous coal (WY) from the Argonne Premium Sample Bank and Black Thunder subbituminous coal (BT) provided by Amoco. Half of the reactions in the matrix have now been completed. In all but one case, Black Thunder-HCl/H{sub 2}O, the ISO proved to be more reactive than TET. After the other four reactions using this combination are complete, the average conversion may be greater with the cyclic olefin. The second part of this paper describes the current and future work with Fourier transform infrared spectroscopy. The objective of this work is to determine the kinetics of reaction of isotetralin at high temperatures and pressures. This quarter combinations of three products typically produced from isotetralin were used in spectral subtraction.

  6. Fine particle clay catalysts for coal liquefaction. Quarterly technical progress report, February 9, 1993--May 8, 1993

    SciTech Connect

    Olson, E.S.

    1995-10-01

    An investigation of new methods for the production and utilization of tetralin-soluble iron oxometallate precursors for coal liquefaction catalysts was continued in this quarter. Further descriptions of the catalytic activities of the sulfided forms were obtained. The hydrogenation activities of catalysts derived from iron oxotitanate and cobalt oxoaluminate were investigated using pyrene as a the test compound, and results were compared with thermal reactions. The hydrogenation activity of iron oxotitanate was superior to other catalysts including iron oxoaluminate. The hydrogenation activity of cobalt oxoaluminate was similar to that of iron oxoaluminate reported in previous quarterly report. The liquefaction of Wyodak subbituminous coal was investigated using in situ sulfided iron oxotitanate catalyst. In order to improve the usefulness of iron oxoaluminate as a liquefaction catalyst, iron oxoaluminate was supported on acid-treated montmorillonite (K-10). Supporting the iron oxoaluminate on an acidic support significantly improved the hydrogenation activity of iron oxoaluminate. The hydrocracking activity was increased by a large factor. Thus the aluminate and titanate structures surrounding the pyrrhotite that forms during sulfidation have a beneficial effect in preventing deactivation of the iron sites, and the presence of the acidic sites in the clay results in effective catalytic synergism between catalyst and support. These clay-supported iron oxometallates are highly promising catalysts for coal liquefaction. Iron oxyhydroxide and triiron supported on acid-treated montmorillonite (K-10) were tested for the liquefaction of ion-exchanged Wyodak (IEW) to minimize effects of the coal mineral matter. Both sulfided catalysts gave very high conversions of coal to THF-soluble and heptane-soluble (oils) products.

  7. Fine particle clay catalysts for coal liquefaction. Quarterly technical progress report, November 9, 1992--February 8, 1993

    SciTech Connect

    Olson, E.S.

    1995-10-01

    The mixed iron/alumina pillared clay catalysts and clay-supported iron catalysts have been shown in previous reports of this project to significantly improve yields of heptane-soluble products obtained in the liquefaction of both as received and acid-exchanged Wyodak subbituminous coal and Blind Canyon bituminous coal. In this quarter, the soluble product (LSW) obtained from the noncatalytic low-severity liquefaction of Wyodak coal was used as a feed to determine the activity of iron based catalysts for the hydrogenation and depolymerization steps. Comparison data for liquefaction of the soluble LSW with other catalysts were desired, and these data were obtained for a dispersed form of iron sulfide, prepared via iron hydroxyoxide (PETC method). The iron oxyhydroxide catalyst was directly precipitated on LSW product using either water or ethanol as the solvent. An insight into the functioning of the mixed iron/alumina pillared clay in coal liquefaction was investigated by preparing and studying an iron oxoaluminate structure. An investigation of new methods for the production of tetralin soluble iron oxometallate catalysts and the determination of their catalytic activities was continued in this quarter. The hydrogenation activity of iron oxoaluminate was investigated using pyrene and 1-methylnaphthalene as the test compounds, and results were compared with thermal reactions. In order to determine the loss of activity, recovered catalyst was recycled a second time for the hydrotreating of pyrene. Reaction of 1-methylnaphthalene with iron oxoaluminate also gave very high conversion to 1- and 5-methyltetralins and small amount of 2- and 6-methyltetralins. Liquefaction of Wyodak subbituminous and Blind Canyon bituminous coal was investigated using an in situ sulfided soluble iron oxoaluminate catalyst.

  8. Aerobic biodegradation kinetics and mineralization of six petrodiesel/soybean-biodiesel blends.

    PubMed

    Yassine, Mohamad H; Wu, Shuyun; Suidan, Makram T; Venosa, Albert D

    2013-05-07

    The aerobic biodegradation kinetics and mineralization of six petrodiesel/soybean-biodiesel blends (B0, B20, B40, B60, B80, and B100), where B100 is 100% biodiesel, were investigated by acclimated cultures. The fatty acid methyl esters (FAMEs) of biodiesel were found to undergo rapid abiotic transformation in all experiments. The C10-C21 n-alkanes of petrodiesel were metabolized at significantly higher microbial utilization rates in the presence of biodiesel. The rates of mineralization of the blends were also enhanced in the presence of biodiesel; yet a similar enhancement in the extent of mineralization was not observed. Abiotic fuel-blends/aqueous-phase equilibration experiments revealed that the FAMEs of biodiesel were capable of cosolubilizing the n-alkanes of petrodiesel, a mechanism that fully explains the faster utilization and mineralization kinetics of petrodiesel in the presence of biodiesel without necessarily enhancing the extent of biomineralization. The biodegradation of six targeted aromatic compounds present in petrodiesel was also influenced by the amount of biodiesel in a blend. While toluene, o-xylene, and tetralin were not degraded in the B0 and B20 treatments, all of the targeted aromatic compounds were degraded to below detection limits in the B40 and B80 treatments. Biomass acclimated to B60, however, was unable to degrade most of the aromatic compounds. These results indicate that the amount of biodiesel in a blend significantly affects the absolute and relative abundance of the dissolved and bioavailable constituents of biodiesel and petrodiesel in a way that can considerably alter the biodegrading capacity of microbial cultures.

  9. Selective hydrogenation of polynuclear heteroatomic compounds. Final report

    SciTech Connect

    Fish, R.H.; Heinemann, H.

    1985-08-01

    This research program focused on the utilization of polymer-supported (polystyrene-divinylbenzene, PS-DVB) transition-metal catalysts in the selective catalytic hydrogenation of polynuclear heteroaromatic compounds that are known to be present in coal and coal liquids. We found that the polymer-supported chlorotris(triphenyl-phosphine)rhodium(1) was the most efficient catalyst for the regiospecific reduction of the nitrogen-containing ring in model-coal compounds such as quinoline, 5,6- and 7,8-benzoquinoline and acridine, and in one case, a heteroaromatic sulfur compound, benzothiophene. Interestingly, the polymer-supported rhodium catalyst was more active than the corresponding homogeneous analogue by relative rate factors of 10 to 20 depending on the substrate studied in the reduction. More importantly, a model coal liquid was found to have a relative rate of reduction of quinoline to 1,2,3,4-tetrahydroquinoline (THQ) that was 2.2 times faster than a similar experiment without the coal liquid constituents consisting of pyrene, tetralin, methylnaphthalene, p-cresol, quinoline, and 2-methylpyridine. Further experimentation clearly showed that the model coal liquid constituent, p-cresol, was responsible for the relative rate enhancement in the highly regiospecific (no other model coal liquid constituent was hydrogenated) reduction of quinoline to THQ. We also found that 9,10-dihydrophenanthridine was an excellent catalytic transfer hydrogenation reagent in the presence of several homogeneous and polymer-supported transition-metal catalysts. A discussion demonstrates the potential usefulness of these catalysts in the hydroprocessing of coal liquids and other petroleum products.

  10. Selective catalytic hydrogenation of polynuclear heteroaromatic compounds using polymer-supported transition-metal compounds as catalyst. [5,6 and 7,8-benzoquinoline and quinoline

    SciTech Connect

    Fish, R.H.; Heinemann, H.

    1985-06-01

    This research program focused on the utilization of polymer-supported (polystyrene-divinylbenzene, PS-DVB) transition-metal catalysts in the selective catalytic hydrogenation of polynuclear heteroaromatic compounds that are known to be present in coal and coal liquids. We found that the polymer-supported chlorotris(triphenyl-phosphine)rhodium(1) was the most efficient catalyst for the regiospecific reduction of the nitrogen-containing ring in model-coal compounds such as quinoline, 5,6- and 7,8-benzoquinoline and acridine, and in one case, a heteroaromatic sulfur compound, benzothiophene. Interestingly, the polymer-supported rhodium catalyst was more active than the corresponding homogeneous analogue by relative rate factors of 10 to 20 depending on the substrate studied in the reduction. More importantly, a model coal liquid was found to have a relative rate of reduction of quinoline to 1,2,3,4-tetrahydroquinoline (THQ) that was 2.2 times faster than a similar experiment without the coal liquid constituents consisting of pyrene, tetralin, methylnaphthalene, p-cresol, quinoline, and 2-methylpyridine. Further experimentation clearly showed that the model coal liquid constituent, p-cresol, was responsible for the relative rate enhancement in the highly regiospecific reduction of quinoline to THQ. Nuclear magnetic resonance spectroscopy (NMR) experiments have given some insight into this rate-enhancement phenomena. We also found that 9,10-dihydrophenanthridine was an excellent catalytic transfer hydrogenation reagent in the presence of several homogeneous and polymer-supported transition-metal catalysts. Hydrogen was transferred to such acceptors as quinoline and acridine. We also evaluated dihydroquinoline as a donor solvent since THQ has been used as a donor solvent in coal liquefaction experiments. 48 refs., 4 figs., 2 tabs.

  11. Spinal serotonin 5-HT7 and adenosine A1 receptors, as well as peripheral adenosine A1 receptors, are involved in antinociception by systemically administered amitriptyline.

    PubMed

    Liu, Jean; Reid, Allison R; Sawynok, Jana

    2013-01-05

    The present study explored a link between spinal 5-HT(7) and adenosine A(1) receptors in antinociception by systemic amitriptyline in normal and adenosine A(1) receptor knock-out mice using the 2% formalin test. In normal mice, antinociception by systemic amitriptyline 3mg/kg was blocked by intrathecal administration of the selective adenosine A(1) receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) 10 nmol. Blockade was also seen in adenosine A(1) receptor +/+ mice, but not in -/- mice lacking these receptors. In both normal and adenosine A(1) receptor +/+ mice, the selective 5-HT(7) receptor antagonist (2R)-1-[(3-hydroxyphenyl)sulfonyl]-2-[2-(4-methyl-1-piperidinyl)ethyl]pyrrolidine hydrochloride (SB269970) 3 μg blocked antinociception by systemic amitriptyline, but it did not prevent antinociception in adenosine A(1) receptor -/- mice. In normal mice, flinching was unaltered when the selective 5-HT(7) receptor agonist (2S)-(+)-5-(1,3,5-trimethylpyrazol-4-yl)-2-(dimethylamino)tetralin (AS-19) 20 μg was administered alone, but increased when co-administered intrathecally with DPCPX 10 nmol or SB269970 3 μg. Intrathecal AS-19 decreased flinching in adenosine A(1) receptor +/+ mice compared to -/- mice. Systemic amitriptyline appears to reduce nociception by activating spinal adenosine A(1) receptors secondarily to 5-HT(7) receptors. Spinal actions constitute only one aspect of antinociception by amitriptyline, as intraplantar DPCPX 10 nmol blocked antinociception by systemic amitriptyline in normal and adenosine A(1) receptor +/+, but not -/- mice. Adenosine A(1) receptor interactions are worthy of attention, as chronic oral caffeine (0.1, 0.3g/L, doses considered relevant to human intake levels) blocked antinociception by systemic amitriptyline in normal mice. In conclusion, adenosine A(1) receptors contribute to antinociception by systemic amitriptyline in both spinal and peripheral compartments.

  12. The use of NMR techniques for the analysis of water in coal and the effect of different coal drying techniques on the structure and reactivity of coal. Final report

    SciTech Connect

    Netzel, D.A.; Miknis, F.P.; Wallace, J.C. Jr.; Butcher, C.H.; Mitzel, J.M.; Turner, T.F.; Hurtubise, R.J.

    1995-02-01

    Western Research Institute has conducted a study of different methods of coal drying as pretreatment steps before liquefaction. The objectives of this study were to develop a combined chemical dehydration/nuclear magnetic resonance (NMR) method for measuring the moisture content of coal, to measure the changes in coal structure that occur during drying, and to determine the effects of different drying methods on liquefaction reactivity of coals. Different methods of drying were investigated to determine whether coal drying can be accomplished without reducing the reactivity of coals toward liquefaction. Drying methods included thermal, microwave, and chemical dehydration. Coals of rank lignite to high volatile bituminous were studied. Coals that were dried or partially dried thermally and with microwaves had lower liquefaction conversions than coals containing equilibrium moisture contents. However, chemically dried coals had conversions equal to or greater than the premoisturized coals. The conversion behavior is consistent with changes in the physical structure and cross linking reactions because of drying. Thermal and microwave drying appear to cause a collapse in the pore structure, thus preventing donor solvents such as tetralin from contacting reactive sites inside the coals. Chemical dehydration does not appear to collapse the pore structure. These results are supported by the solvent swelling measurements in which the swelling ratios of thermally dried and microwave-dried coals were lower than those of premoisturized coals, indicating a greater degree of cross linking in the dried coals. The swelling ratios of the chemically dried coals were greater than those of the premoisturized coals because the pore structure remaining unchanged or increased when water was removed. These results are consistent with the NMR results, which did not show significant changes in coal chemical structure.

  13. A structural investigation of the effect of catalysis on the liquefaction products of a brown and a bituminous Australian Coal

    SciTech Connect

    Strachan, M.G.; Johns, R.B.; Vassallo, A.M.

    1983-01-01

    The paper reports a study comparing the effects of a single catalyst, Co/Mo, on two Australian coals of different rank at their uncatalyzed optimal oil yield temperatures under donor solvent conditions. It was considered more appropriate to compare the products from the two coals at their respective optimal oil yield temperatures rather than at the same temperature. The former accounts and compensates for differing thermal reactivities with rank, thereby allowing a direct comparison of product qualities to be made. The coals used for the study were a Victorian brown coal, LY1277, from the Loy Yang Field, a medium-light lithotype, and a N.S.W. high volatile bituminous coal from the Liddell Field. They were chosen because of their known liquefaction potential. They were reacted at 375/sup 0/C and 425/sup 0/C respectively, in batch autoclaves using a solvent (tetralin) coal ratio of 2:1, a catalyst concentration of 10% w/w coal and were reacted for 2 hours at temperature. The total liquid product (TLP) (defined as CH/sub 2/Cl/sub 2/ solubles) was fractionated by a separation method designed specifically to separate by functionality into chemically defined classes viz. acids, bases and neutrals. This method utilizes a sequence of ion-exchange resins and silica adsorption chromatography. A feature of the method is that it does not remove the donor solvent until all the polar material is absent, hence alleviating the risk of thermal alteration of the samples as may occur with an initial dissolution step. The method is very effective in class separation.

  14. Tailoring Silica-alumina Supported Pt-Pd As Poison Tolerant Catalyst For Aromatics Hydrogenation

    SciTech Connect

    Yu, Yanzhe; Gutierrez, Oliver Y.; Haller, Gary L.; Colby, Robert J.; Kabius, Bernd C.; Rob van Veen, J. A.; Jentys, Andreas; Lercher, Johannes A.

    2013-08-01

    The tailoring of the physicochemical and catalytic properties of mono- and bimetallic Pt-Pd catalysts supported on amorphous silica-alumina is studied. Electron energy loss spectroscopy and extended X-ray absorption fine structure analyses indicated that bimetallic Pt-Pd and relatively large monometallic Pd particles were formed, whereas the X-ray absorption near edge structure provided direct evidence for the electronic deficiency of the Pt atoms. The heterogeneous distribution of metal particles was also shown by high resolution transmission electron microscopy. The average structure of the bimetallic particles (Pt-rich core and Pd-rich shell) and the presence of Pd particles led to surface Pd enrichment, which was independently shown by IR spectra of adsorbed CO. The specific metal distribution, average size, and surface composition of the Pt-Pd particles depend to a large extent on the metal precursors. In the presence of NH3 ligands, Pt-Pd particles with a fairly homogeneous bulk and surface metal distribution were formed. Also high Lewis acid site concentration of the carrier leads to more homogeneous bimetallic particles. All catalysts were active for the hydrogenation of tetralin in the absence and presence of quinoline and dibenzothiophene (DBT). Monometallic Pt catalysts had the highest hydrogenation activity in poison-free and quinoline-containing feed. When DBT was present, bimetallic Pt-Pd catalysts with the most homogenous metal distribution showed the highest activity. The higher resistance of bimetallic catalysts towards sulfur poisoning compared to their monometallic Pt counterparts results from the weakened metal-sulfur bond on the electron deficient Pt atoms. Thus, increasing the fraction of electron deficient Pt on the surface of the bimetallic particles increases the efficiency of the catalyst in the presence of sulfur.

  15. An extensible framework for capturing solvent effects in computer generated kinetic models.

    PubMed

    Jalan, Amrit; West, Richard H; Green, William H

    2013-03-14

    Detailed kinetic models provide useful mechanistic insight into a chemical system. Manual construction of such models is laborious and error-prone, which has led to the development of automated methods for exploring chemical pathways. These methods rely on fast, high-throughput estimation of species thermochemistry and kinetic parameters. In this paper, we present a methodology for extending automatic mechanism generation to solution phase systems which requires estimation of solvent effects on reaction rates and equilibria. The linear solvation energy relationship (LSER) method of Abraham and co-workers is combined with Mintz correlations to estimate ΔG(solv)°(T) in over 30 solvents using solute descriptors estimated from group additivity. Simple corrections are found to be adequate for the treatment of radical sites, as suggested by comparison with known experimental data. The performance of scaled particle theory expressions for enthalpic-entropic decomposition of ΔG(solv)°(T) is also presented along with the associated computational issues. Similar high-throughput methods for solvent effects on free-radical kinetics are only available for a handful of reactions due to lack of reliable experimental data, and continuum dielectric calculations offer an alternative method for their estimation. For illustration, we model liquid phase oxidation of tetralin in different solvents computing the solvent dependence for ROO• + ROO• and ROO• + solvent reactions using polarizable continuum quantum chemistry methods. The resulting kinetic models show an increase in oxidation rate with solvent polarity, consistent with experiment. Further work needed to make this approach more generally useful is outlined.

  16. Small and Innovative Molecules as New Strategy to Revert MDR.

    PubMed

    Zinzi, Laura; Capparelli, Elena; Cantore, Mariangela; Contino, Marialessandra; Leopoldo, Marcello; Colabufo, Nicola Antonio

    2014-01-01

    Multidrug resistance (MDR) is a complex phenomenon principally due to the overexpression of some transmembrane proteins belonging to the ATP binding cassette (ABC) transporter family. Among these transporters, P-glycoprotein (P-gp) is mostly involved in MDR and its overexpression is the major cause of cancer therapy failure. The classical approach used to overcome MDR is the co-administration of a P-gp inhibitor and the classic antineoplastic drugs, although the results were often unsatisfactory. Different classes of P-gp ligands have been developed and, among them, Tariquidar has been extensively studied both in vitro and in vivo. Although Tariquidar has been considered for several years as the lead compound for the development of P-gp inhibitors, recent studies demonstrated it to be a substrate and inhibitor, in a dose-dependent manner. Moreover, Tariquidar structure-activity relationship studies were difficult to carry out because of the complexity of the structure that does not allow establishing the role of each moiety for P-gp activity. For this purpose, SMALL molecules bearing different scaffolds such as tetralin, biphenyl, arylthiazole, furoxane, furazan have been developed. Many of these ligands have been tested both in in vitro assays and in in vivo PET studies. These preliminary evaluations lead to obtain a library of P-gp interacting agents useful to conjugate chemotherapeutic agents displaying reduced pharmacological activity and appropriate small molecules. These molecules could get over the limits due to the antineoplastic-P-gp inhibitor co-administration since pharmacokinetic and pharmacodynamic profiles are related to a dual innovative drug.

  17. Experimental and computational study of methane counterflow diffusion flames perturbed by trace amounts of either jet fuel or a 6-component surrogate under non-sooting conditions

    SciTech Connect

    Bufferand, H.; Tosatto, L.; La Mantia, B.; Smooke, M.D.; Gomez, A.

    2009-08-15

    The chemical structure of a methane counterflow diffusion flame and of the same flame doped with 1000 ppm (molar) of either jet fuel or a 6-component jet fuel surrogate was analyzed experimentally, by gas sampling via quartz microprobes and subsequent GC/MS analysis, and computationally using a semi-detailed kinetic mechanism for the surrogate blend. Conditions were chosen to ensure that all three flames were non-sooting, with identical temperature profiles and stoichiometric mixture fraction, through a judicious selection of feed stream composition and strain rate. The experimental dataset provides a glimpse of the pyrolysis and oxidation behavior of jet fuel in a diffusion flame. The jet fuel initial oxidation is consistent with anticipated chemical kinetic behavior, based on thermal decomposition of large alkanes to smaller and smaller fragments and the survival of ring-stabilized aromatics at higher temperatures. The 6-component surrogate captures the same trend correctly, but the agreement is not quantitative with respect to some of the aromatics such as benzene and toluene. Various alkanes, alkenes and aromatics among the jet fuel components are either only qualitatively characterized or could not be identified, because of the presence of many isomers and overlapping spectra in the chromatogram, leaving 80% of the carbon from the jet fuel unaccounted for in the early pyrolysis history of the parent fuel. Computationally, the one-dimensional code adopted a semi-detailed kinetic mechanism for the surrogate blend that is based on an existing hierarchically constructed kinetic model for alkanes and simple aromatics, extended to account for the presence of tetralin and methylcyclohexane as reference fuels. The computational results are in reasonably good agreement with the experimental ones for the surrogate behavior, with the greatest discrepancy in the concentrations of aromatics and ethylene. (author)

  18. Data base for the analysis of compositional characteristics of coal seams and macerals. Quarterly technical progress report, May-July 1980

    SciTech Connect

    Davis, Alan; Suhr, N. H.; Spackman, W.; Painter, P. C.; Walker, P. L.; Given, P. H.

    1980-10-01

    The basic objectives of this new program are, firstly, to understand the systematic relationships between the properties of coals and macerals, and, secondly, to determine the lateral and vertical variability in the properties of a single seam imposed by varying environmental conditions at the time of coal formation. Thirty-four coal samples were collected during the quarter from Pennsylvania and Illinois. To date, 54 vitrinite concentrates have been hand picked and will be studied by a range of physical and chemical techniques. One hundred and forty coal samples and 53 printouts of coal data were provided on request to the coal research community. The Lower Kittanning seam has been selected for the study of the variability in chemical, petrographic, mineralogic, fluid, and conversion properties of a single seam. A description of the structural and stratigraphic settings of the important coal seam as they relate to this investigation is given. Bivariate plots of data from the Lower Kittanning seam are presented. The fluid temperature range as measured with the Gieseler plastometer reaches a maximum at a reflectance of 1.10 to 1.15% and carbon content of 87 to 88% dmmf. Liquefaction conversion in a tubing-bomb reactor with tetralin shows a linear decrease with rank (reflectance). The problems associated with the application Fourier Transform Infrared Spectroscopy to the characterization of coal structure are critically discussed. The micropore surface areas and micropore volumes of three selected coals and a vitrinite concentrate, as measured from uptake of CO/sub 2/ at 25/sup 0/C, increased with decreasing particle size. Work on measurements of apparent densities and uptake of methanol and water is in progress.

  19. Dopaminergic D2-like agonists produce yawning in the myelin mutant taiep and Sprague-Dawley rats.

    PubMed

    Eguibar, Jose R; Cortes, Ma del Carmen; Lara-Lozano, Manuel; Mendiola, Diana M

    2012-07-01

    Systemic administration of D2-like dopaminergic-receptor agonists increases yawning behavior. However, only a few studies have been done in animals with pathological conditions. The taiep rat is a myelin mutant with an initial hypomyelination followed by progressive demyelination, being the brainstem one of the most affected areas. In our experiments, we analyzed the effects of systemic administration of the D2-family agonists and antagonists on yawning behavior, and correlated them with the lipid myelin content in the brainstem and other areas in the central nervous system (CNS) in 8 month old male taiep and Sprague-Dawley rats. Subjects were maintained under standard conditions in Plexiglas cages with a 12:12 light-dark cycle, lights on at 0700 and free access to rodent pellets and tap water. Drugs were freshly prepared injected ip at 0800 and subjects were observed for 60 min. When antagonists were used it was administered 15 min before the agonist. Sprague-Dawley and taiep rats significantly increased their yawning frequency after systemic injection of (-)-quinpirole hydrochloride, R(+)-7-Hydroxy-2-(dipropylamino)tetralin hydrobromide (7-OH-DPAT) or trans-(±)-3,4,4a,10b-tetrahydro-4-propyl-2H,5H-[1]benzopyrano [4,3-b]-1,4-oxazin-9-ol hydrochloride ((±)-PD 128,907). Among D2-like agonists used higher effects are obtained with (-)-quinpirole. The effects caused by (-)-quinpirole can be reduced by (-)-sulpiride; and yawning caused by 7-OH-DPAT was decreased by tiapride only in taiep rats. In Sprague-Dawley only (-)-sulpiride is able to decrease (-)-quinpirole-caused yawning. In conclusion, dopaminergic D2-like agonists are still able to cause yawning despite the severe myelin loss in taiep rats. Similarly, patients with various CNS illnesses that affect myelin, such as stroke or multiple sclerosis, are able to yawn suggesting that trigger neurons are still able to command this innate behavior.

  20. Fundamental studies of coal liquefaction. Quarterly report No. 7, April 1--July 1, 1993

    SciTech Connect

    Ross, D.S.

    1993-07-14

    In our last report we discussed observations in our cell concerning the behavior or Illinois No. 6 coal in tetralin to 460{degrees}C. We noted that there were possibly two distinct types of particles comprising the organic phase, reacting respectively at 420{degrees}--430{degrees}C, and at 450{degrees}--460{degrees}C. Alternatively we could interpret the data as describing a range of reactivity bounded by those temperatures. As evidenced by the contraction of the particles, the reactions were rapid. The particles lost half of their substance within 1 min, and we suggested that the rates were too fast to be accommodated by the commonly held scheme for coal liquefaction involving thermolytic scission of weak, bibenzyl-like bonds. Our analyses were aided by our use of Adobe Photoshop, which allows us to store, digitized versions of our recorded images. The images can then be manipulated at will to provide quantitative data on morphological changes. We noted in our last report that printer limitations prevented us from presenting images with the desirable quality, and we are at present attempting to find access to equipment which will provide satisfactory figures. Accordingly our progress will be described here without any photographs, and we expect to present a more complete account of our work in our next report. The work reported here includes studies of Illinois No. 6 coal with water as the medium, and a control run with argon as medium. Our temperature ramping was like that used last time, 25{degrees}C/min to 250{degrees}C, and then 10{degrees}C/min to 450{degrees}C. The results from the earlier work and the data presented here can therefore be directly compared.

  1. Diffusive transport processes in microgravity: the DCMIX project and the path to DCMIX-3

    NASA Astrophysics Data System (ADS)

    Triller, Thomas; Köhler, Werner

    2016-07-01

    Thermodiffusion describes the demixing of a system under the influence of an external temperature gradient which drives diffusive mass fluxes. Over the years, several (ground based) optical techniques have been employed for measuring thermodiffusion: Thermal Diffusion Forced Rayleigh Scattering (TDFRS), Optical Digital Interferometry (ODI) or Optical Beam Deflection (OBD). Most of these experiments use the same mechanism for the detection of demixing: light passes through a thermodiffusion cell, in which a well defined temperature gradient is applied on the sample. Diffusive fluxes change the concentration profile across the cell, and therefore the refractive index profile. This refractive index change is detected and mapped to the concentration using proper optical contrast factors. In particular ternary and higher multicomponent systems can suffer from thermosolutal convective instabilities. Therefore, the DCMIX project, a collaboration between several international research teams, ESA and Roscosmos, spearheads a measurement campaign on the ISS, utilizing SODI (Selectable Optical Diagnostics Instrument), a Mach-Zehnder interferometer inside the Microgravity Science Glovebox. Several ternary mixtures have been selected for measurement, all exhibiting unique properties. DCMIX-1 consisted of tetralin/isobutylbenzene/dodecane, a good model for hydrocarbon mixtures. DCMIX-2 was the system toluene/methanol/cyclohexane, which has a miscibility gap and allows to study critical behavior. DCMIX-3 is planned for the end of 2016 and will be an aqueous mixture of water/ethanol/triethylene-glycol. After a setback in 2014, when DCMIX-3 samples were lost with the explosion of the unmanned Orb3 vehicle, the project is now underway and will be ready for analysis at the beginning of 2017. As preparation for this, the methodology developed for data analysis has been applied to the DCMIX-1 data, especially aiming for the identification of stable quantities, which allow utilization of

  2. Improved performance in coprocessing through fundamental and mechanistic studies in hydrogen transfer and catalysis. Final report, September 26, 1989--March 31, 1993

    SciTech Connect

    Curtis, C.W.

    1993-12-31

    The key results obtained from this research project are given: (1) Hydrogen transfer from naphthenes to aromatics, coal and resid occurred at coprocessing temperatures and in a N{sub 2} atmosphere; (2) Hydrogen donors ranked in reactivity as cyclic olefins (nonaromatic hydroaromatic compounds) > hydroaromatic compounds > naphthenes. This ranking held regardless of the type of atmosphere, hydrogen or nitrogen, used; (3) Resids reduced by the Birch method transferred substantially more hydrogen to the aromatic acceptor than did the parent resids under coprocessing conditions; (4) Hydropretreatment of resids resulted in enhanced coal conversion compared to the parent resid; (5) Addition of hydrogen donors such as cyclic olefins or hydroaromatic donors increased the amount of coal conversion during coprocessing. Cyclic olefins and the active hydroaromatic donor, dihydroanthracene, showed the highest level of hydrogen donability. Tetralin and octahydroanthracene showed low reactivity; (6) Reduced resids were more effective in coprocessing than the parent resids, in terms of enhanced coal conversion; (7) Thermal and catalytic reactivity of cyclic olefins under nitrogen and hydrogen atmospheres was much higher than conventional hydroaromatic donors when no aromatic acceptor was present; (8) Reactivity of hydrogen donors was dependent upon the reactivity of the acceptor as well as that of the donors; (9) Three-ring hydrogen donors, dihydroanthracene and hexahydroanthracene, were most effective for transferring hydrogen to the Argonne coals while octahydroanthracene was the least reactive; (10) The kinetics data obtained for thermal and catalytic reactions involving cyclic olefins and hydroaromatic donors were adequately modeled by pseudo-first order kinetics; and (11) {Delta}G values calculated for cyclic olefins and hydroaromatic donors based on kinetics data adequately represented the reactivity observed experimentally.

  3. Thermodynamic model for calorimetric and phase coexistence properties of coal derived fluids. Final technical report

    SciTech Connect

    Kabadi, V.N.

    1992-10-01

    The work on this project was initiated on September 1, 1989. The project consisted of three different tasks. 1. A thermodynamic model to predict VLE and calorimetric properties of coal liquids. 2. VLE measurements at high temperature and high pressure for coal model compounds and 3. Chromatographic characterization of coal liquids for distribution of heteroatoms. The thermodynamic model developed is an extension of the previous model developed for VLE of coal derived fluids (DOE Grant no. FG22-86PC90541). The model uses the modified UNIFAC correlation for the liquid phase. Some unavailable UNIFAC interactions parameters have been regressed from experimental VLE and excess enthalpy data. The model is successful in predicting binary VLE and excess enthalpy data. Further refinements of the model are suggested. An apparatus for the high pressure high temperature VLE data measurements has been built and tested. Tetralin-Quinoline is the first binary system selected for data measurements. The equipment was tested by measuring 325{degree}C isotherm for this system and comparing it with literature data. Additional isotherms at 350{degree}C and 370{degree}C have been measured. The framework for a characterization procedure for coal derived liquids has been developed. A coal liquid is defined by a true molecular weight distribution and distribution of heteroatoms as a function of molecular weights. Size exclusions liquid chromatography, elemental analysis and FTIR spectroscopy methods are used to obtain the molecular weight and hetroatom distributions. Further work in this area should include refinements of the characterization procedure, high temperature high pressure VLE data measurements for selective model compound binary systems, and improvement of the thermodynamic model using the new measured data and consistent with the developments in the characterization procedure.

  4. Low severity coal liquefaction promoted by cyclic olefins. Quarterly report, July--September 1993

    SciTech Connect

    Curtis, C.W.

    1993-12-31

    Low-severity coal liquefaction allows for the solubilization of coal with reduced gas make. The idea being tested in this research is whether selective bond rupture occurs during liquefaction at low temperatures that can be satisfied by hydrogen donation from highly active hydrogen donor compounds. Promotion of coal solubilization through hydrogen transfer using highly active and effective hydrogen donors is the objective of this study. The highly effective hydrogen donors being tested are cyclic olefins. Representative cyclic olefins are isotetralin (ISO), which is 1,4,5,8-tetrahydronaphthalene, and 1,4,5,8,9, 10hexahydroanthracene (HHA). These compounds have been shown to highly effective donors (Bedell and Curtis, 1991) which release their hydrogen at fairly low temperatures, in the 200 to 300{degrees}C range. ISO has been shown to be much more effective than its hydroaromatic analogue tetralin (TET) in releasing hydrogen at low temperatures and transferring that hydrogen to an acceptor molecule or to coal (Bedell and Curtis, 1991). Likewise, at 380{degrees}C, the ability of HHA to release hydrogen in both N{sub 2} and H{sub 2} atmospheres was greater than a comparative hydroaromatic compound, dihydroanthracene (DHA). However, when an acceptor molecule or coal was present, DHA was as or more active than HHA in transferring hydrogen (Bedell et al., 1993). In another study, at equivalent reaction conditions and in the presence of anthracene (ANT) as a hydrogen acceptor, ISO released more than 200 times as much hydrogen as TET and HHA released 18 to 25 times as much hydrogen as DHA (Wang, 1992).

  5. An investigation of the role of water on retrograde/condensation reactions and enhanced liquefaction yields. Final report

    SciTech Connect

    Miknis, F.P.; Netzel, D.A.; Wallace, J.C. Jr.; Butcher, C.H.; Mitzel, J.M.; Turner, T.F.

    1995-02-01

    While great strides have been made in developing the technology of coal liquefaction processes in recent years, many unsolved problems still remain before a viable and economical process can be achieved. The technological problems that still exist can be solved through a more fundamental understanding of the chemistry associated with each stage of the coal liquefaction process, starting with any pretreatment steps that may be carried out on the coal itself. Western Research Institute, under the a contract from the US Department of Energy, has conducted a study of different methods of coal drying as pretreatment steps before liquefaction. The results of that study are the subject of this report. Coals that were dried or partially dried thermally and with microwaves had lower liquefaction conversions than coals containing equilibrium moisture contents. However, chemically dried coals had conversions equal to or greater than the premoisturized coals. The conversion behavior is consistent with changes in the physical structure and cross linking reactions because of drying. Thermal and microwave drying appear to cause a collapse in the pore structure, thus preventing donor solvents such as tetralin from contacting reactive sites inside the coals. Chemical dehydration does not appear to collapse the pore structure. From the study of the kinetics of the chemical dehydration of coals, it was possible to quantify the amount of water on the surface, the amount readily accessible in pores, and the amount more strongly bonded in the internal structure of the coals. The results indicate that high-rank coals have proportionally less surface and easily accessible water than the lower rank coals.

  6. a First-Principles Model of Fermi Resonance in the Alkyl CH Stretch Region: Application to Hydronaphthalenes, Indanes, and Cyclohexane

    NASA Astrophysics Data System (ADS)

    Sibert, Edwin; Kidwell, Nathanael; Zwier, Timothy S.

    2014-06-01

    The infrared (IR) spectroscopy of the alkyl CH stretch region (2750-3000 cm-1) of a series of bicyclic hydrocarbons and free radicals has been studied under supersonic expansion cooling in the gas phase, and compared with a theoretical model that describes the local mode stretch-bend Fermi resonance interactions. The double resonance method of fluorescence-dip infrared (FDIR) spectroscopy was used on the stable molecules 1,2-dihydronaphthalene, 1,4-dihydronaphthalene, tetralin, indene, and indane using the S_0-S_1 origin transition as a monitor of transitions. Resonant ion-dip infrared (RIDIR) spectra were recorded for the trihydronaphthyl (THN) and inden-2-yl methyl (I2M) radicals. The previously developed model Hamiltonian [J. Chem. Phys. 138 064308 (2013)] incorporates cubic stretch-bend coupling with parameters obtained from density functional theory methods. Full dimensional calculations are compared to reduced dimensional Hamiltonian results in which anharmonic CH streches and CH_2 scissor modes are Fermi coupled. Excellent agreement between theoretical results is found. Scale factors of select terms in the reduced dimensional Hamiltonian, obtained by fitting the theoretical Hamiltonian predictions to the experimental spectra, are found to be similar to previous work. The resulting Hamiltonian predicts successfully all the major spectral features considered in this study. A simplified model is introduced in which the CH_2 groups are decoupled. This model enables the assignment of many of the spectral features. The model results are extended to describe the CH stretch spectrum of the chair and twist-boat conformers of cyclohexane. The chair conformer is used to illustrate the shortcomings of the CH_2 coupling model.

  7. Data base for the analysis of compositional characteristics of coal seams and macerals. Quarterly technical progress report, August-October 1980

    SciTech Connect

    Davis, Alan; Suhr, N. H.; Spackman, W.; Painter, P. C.; Walker, P. L.; Given, P. H.

    1981-02-01

    A total of 69 samples have been obtained from the Lower Kittanning seam in western Pennyslvania and eastern Ohio. The samples were taken from 39 sample sites and consist of 39 channel samples and 30 hand-picked vitrinites. A complex statistical analysis of petrographic, physical and chemical properties of these samples was performed in order to study their relationship with thermoplastic and liquefaction behavior. The parameters of the thermoplastic properties were obtained using a Gieseler plastometer. The liquefaction conversion with tetralin was determined in tubing bomb reactors at 400/sup 0/C for 1 hour. Factor analysis on the whole sample population indicated that both liquefaction conversion and some of the measured thermoplastic properties are significantly related with rank. Temperature of softening and degree of fluidity, however, did not load on the rank component. /sup 13/C nmr spectra were obtained for six of our vitrinite concentrates by the University of Utah. The aromaticities determined for fairly wide rank range of these samples varied only from 0.66 to 0.72. However the series showed progression from highly functional aromatic structure at low rank to one with little functionality at high rank. The spectra show no indication of a consistent loss in aliphatic oxygen. The surface areas and micropore volumes of two fractions, -20 and -100 mesh, of five vitrinite concentrates have been measured from CO/sub 2/ uptake at 25/sup 0/C. An increase in these values is observed with decreasing particle size. Total open pore volumes were calculated from particle and helium densities.

  8. Characterization of selected Ohio coals to predict their conversion behavior relative to 104 North American Coals. [Factors correlating with liquefaction behavior

    SciTech Connect

    Whitacre, T. P.; Hunt, T. J.; Kneller, W. A.

    1982-02-01

    Twenty-six coal samples from Ohio were collected as washed and seam samples, and lithobodies within the seams. Characterization of these samples included determination of % maceral, % anti R/sub max/, LTA, chlorine content and proximate/ultimate and qualitative mineral analyses. These data were compared to data from a similar project by Yarzab, R.F., et al., 1980 completed at Pennsylvania State University using tetralin as the hydrogen donor solvent. The characteristics of these coals were correlated with liquefaction conversion and other data accrued on 104 North American coals by statistical analyses. Utilizing percent carbon, sulfur, volatile matter, reflectance, vitrinite and total reactive macerals, Q-mode cluster analysis demonstrated that Ohio coals are more similar to the coals of the Interior province than to those of the Appalachian province. Linear multiple regression analysis for the 104 North American coals provided a prediction equation for conversion (R = .96). The predicted conversion values for the samples range from 58.8 to 79.6%, with the Lower Kittanning (No. 5) and the Middle Kittanning (No. 6) coal seams showing the highest predicted percent conversion (respectively, 73.4 and 72.2%). The moderately low FSI values for the No. 5 and No. 6 coals (respectively, 2.5 and 3) and their moderately high alkaline earth content (respectively, 0.69 and 0.74%) suggest that these coals possess the best overall properties for conversion. Stepwise regression has indicated that the most important coal characteristics affecting conversion are, in decreasing order of importance: % volatile matter, % vitrinite and % total sulfur. Conversion processes can be expected to produce higher yields with Ohio coals due to the presence of such mineral catalysts as pyrite and kaolinite. It is believed that the presence of these disposable catalysts increases the marketability of Ohio coals.

  9. Steam pretreatment for coal liquefaction. Final report, September 26, 1990--March 18, 1995

    SciTech Connect

    Graff, R.A.; Balogh-Nair, V.; Ivanenko, O.; Brathwaite, C.

    1995-10-16

    The objective of this study is to demonstrate the use of subcritical steam to pretreat coal for slurry liquefaction, allowing liquefaction to be carried out at lower severity and improving product yield and quality. Samples of Illinois No. 6 coal were pretreated in 750 psia steam at 340{degree}C for 15 minutes. These samples, as well as raw coal, were liquefied at high (400{degree}C, 30 min.) and low (385{degree}C, 15 min.) severity conditions under 1500 psia hydrogen with tetralin as the donor solvent. Improved yields were obtained at both conditions. (Improved yields were not obtained at a liquefaction temperature of 350{degree}C as that put the sample into the region of retrogressive reactions). The deleterious effects of slow heating and exposure of the sample to air were demonstrated. Under low severity conditions, steam pretreatment more that doubled the oil yield, increasing it from 12.5 to 29 wt %. Tests were also conducted with aromatic ethers as model compounds. These were exposed to inert gas and steam at pretreatment conditions and in some cases to liquid water at 315{degree}C. {alpha}-Benzylnaphthyl ether and {alpha}- naphthylmethyl phenyl ether show little difference in conversion and product distribution when the thermolysis atmosphere is changed from inert gas to steam. However when these compounds were reacted in the presence of 5 {angstrom} zeolite, the yields of the thermolysis products improved. Zeolite proved effective in suppressing isomerization of the starting materials. These results suggested that zeolites might be beneficial in steam pretreatment of coal and in coal liquefaction. Pretreatment and liquefaction of mixtures of coal and zeolites increases yields of asphaltenes and preasphaltenes.

  10. [Spectroscopic study on interaction of rodenticide brodifacoum with bovine serum albumin].

    PubMed

    Duan, Yun-Qing; Lei, Huan-Gui; Min, Shun-Geng; Duan, Zhi-Qing

    2009-11-01

    The mutual interaction of bovine serum albumin (BSA) with brodifacoum (3-[3-(4'-bromophenyl-4) 1,2,3,4-tetralin-10]-4-hydroxyl-coumarin), an anticoagulant rodenticide, was investigated by ultra-violet spectroscopy, flurorescence spectroscopy and synchronous fluorescence spectroscopy under physiological conditions. It was proved that the intrinsic fluorescence quenching of BSA by brodifacoum was the result of the formation of brodifacoum-BSA complex. And this quenching is mainly due to static fluorescence quenching. The quenching rate constant (K(sv)), binding site number (n) and binding constant (KA) at different temperatures were calculated from the double reciprocal Lineweaver-Burk plots and the quenching function of lg[(F0 - F)/F] - lg[Q] plots. The thermodynamic parameters indicated that the process of binding was a spontaneous molecular interaction and the hydrophobic force played a major role in stabilizing the brodifacoum BSA complex. The binding distance r between brodifacoum and BSA was 2.84 and 2.87 nm at 20 and 30 degrees C, respectively, which was obtained based on Forster theory of non-radiation energy transfer. The synchronous spectroscopy of BSA and brodifacoum-BSA revealed that the BSA conformation had changed in the presence of brodifacoum. The binding mode and interaction mechanism were suggested as follows: brodifacoum molecules are closed with amino acid residues with electric charge on the hydrophobic cavities of BSA by electrostatic interaction, and binded to the Trp212 residues inside of BSA hydrophobic cavities by hydrophobic interaction force, thereby changed the microenvironment around the Trp residues. The interaction prevented the energy transfer between Tyr and Trp residues, moreover, caused to a non-radiation energy transfer from Trp residues in BSA to brodifacoum, and finally leaded of the quenching the intrinsic fluorescence of BSA.

  11. Fundamental Kinetics of Supercritical Coal Liquefaction: Effect of Catalysts and Hydrogen-Donor Solvents

    SciTech Connect

    McCoy, Ben J; Madras, Girodhar; Smith, J M; Kodera, Yoichi

    1997-04-16

    This is the quarterly report on our recent progress toward the overall objective to understand the supercritical fluid extraction of hydrocarbons from coal. Our strategy is to simulate coal as a high molecular-weight polymeric material by studying the degradation of polymers under various conditions. The hypothesis we are testing is that degradation of such macromolecules is applicable to the decomposition (depolymerization) of the coal network. Polymer degradation and coal liquefaction are influenced strongly by the solvent in the reaction. This motivated our investigation of the effect of hydrogen donor solvents on polymer degradation. In particular, we obtained new experimental data to show how a hydrogen donor, 6-hydroxy tetralin, influences the degradation rate of polystyrene. We also developed a detailed radical mechanism for hydrogen donation based on the Rice-Herzfeld chain reaction concept with the elementary steps of initiation, depropagation, hydrogen abstraction, and termination. Expressions for the degradation rate parameters were obtained by applying continuous distribution kinetics to the MWD of the reacting polymer. The theory explains the different influences of the hydrogen donor solvent on the degradation rate coefficients for different polymers. Though developed for the degradation of polymers, the mechanism and the theory are potentially applicable for chain scission and addition reactions among distributions of paraffins, olefins, and radicals of all chain lengths. The concepts can, in principle, be extended to examine the effect of hydrogen donors on coal liquefaction and on the complex mixture of liquefaction compounds. Based on this work, a research paper titled "Effect of Hydrogen Donors on Polymer Degradation", has been submitted for publication. Our research paper entitled, "Molecular weight effect on the dynamics of polystyrene degradation", has been accepted for publication by the journal, Industrial and Engineering Chemistry Research.

  12. Development of novel PET probe [¹¹C](R,R)HAPT and its stereoisomer [¹¹C](S,S)HAPT for vesicular acetylcholine transporter imaging: a PET study in conscious monkey.

    PubMed

    Nishiyama, Shingo; Ohba, Hiroyuki; Kobashi, Tatsuhiro; Nakamasu, Yumi; Nakao, Hidekazu; Ogata, Tokutaro; Kitashoji, Takeru; Tsukada, Hideo

    2014-07-01

    Carbon-11-labeled (R,R)trans-8-methyl-2-hydroxy-3-[4-[2-aminophenyl]piperizinyl]-tetralin ([(11)C](R,R)HAPT) and its stereoisomer [(11)C](S,S)HAPT were developed for imaging vesicular acetylcholine transporters (VAChTs), exclusively located in presynaptic cholinergic neurons. Both positron emission tomography (PET) probes were evaluated in the brain of conscious monkey (Macaca mulatta) using high-resolution PET. Time-activity curves (TACs) of [(11)C](R,R)HAPT peaked within 5 min after the injection in all regions except the caudate and putamen, both of which showed peaks around 20 min postinjection. The regional distribution patterns of [(11)C](R,R)HAPT determined as total distribution volume (V(t)) were highest in the putamen, high in the caudate, intermediate in the amygdala, hippocampus, and thalamus, lower in the cingulate gyrus and frontal, temporal, and occipital cortices, and lowest in the cerebellum. In contrast, the distribution and TACs of [(11)C](S,S)HAPT were homogeneous in all regions. The uptake of [(11)C](R,R)HAPT was reduced by 1 mg/kg (-)-vesamicol, a specific VAChT antagonist, in all regions except the cerebellum, but not by 0.1 mg/kg SA4503, a specific sigma-1 receptor agonist. These results well reflect the in vitro affinity assessments using rat cerebral membranes. They also demonstrate that [(11)C](R,R)HAPT is a potential PET probe for noninvasive and quantitative imaging of VAChT in the living brain.

  13. Facilitated and selective oxidation of thiophenic sulfur compounds using MoOx/Al₂O₃-H₂O₂ system under ultrasonic irradiation.

    PubMed

    Akbari, Azam; Omidkhah, Mohammadreza; Towfighi Darian, Jafar

    2015-03-01

    Oxidative desulfurization of thiophenic sulfur compounds of benzothiophene (BT), dibenzothiophene (DBT) and 4,6-dimethyl dibenzothiophene (4,6-DMDBT) with MoOx/Al₂O₃ catalyst and H₂O₂ oxidant has been facilitated and more selective under ultrasonic irradiation. The catalyst with the optimum 10% of Mo loading consisted of isolated tetrahedral molybdenum oxide species based on FTIR analysis. The increase of Mo loading to 15% and 20% caused to generation of polymolybdate and MoO₃ crystals which decreased desulfurization activity. Sonication enhanced the apparent reaction rate constants in oxidation of all three sulfur compounds. An increase in the Arrhenius factor (A0), which is the total number of collisions per second, could explain the acceleration in the rate constants by sonication. The apparent activated energy (Ea) of BT oxidation was reduced from 96.6 to 75.3 kJ/mol by using ultrasound. This indicated that ultrasound had also a chemical effect, like a catalytic influence, in the acceleration of BT removal. DBT oxidation was reduced when investigated in the presence of tetralin, naphthalene and 2-methyl naphthalene as the model aromatic compounds of actual light oils. A higher selectivity toward DBT elimination in the presence of aromatics was obtained by sonication when compared with the silent treatment. Ultrasound cleaned the catalyst surface from adsorbed aromatics. On the basis of the obtained results, a mechanistic proposal for this desulfurization was explained. Oxidation was performed by nucleophilic attack of sulfur atom to the molybdenum peroxide species of tetrahedral molybdates, which was more advanced by sonication.

  14. Central serotonergic systems in the spontaneously hypertensive and Lewis rat strains that differ in the elevated plus-maze test of anxiety.

    PubMed

    Kulikov, A; Aguerre, S; Berton, O; Ramos, A; Mormede, P; Chaouloff, F

    1997-05-01

    The spontaneously hypertensive (SHR) and Lewis (LEW) strains differ in numerous behavioral tests, including the elevated plus-maze. In keeping with the crucial role of central serotonin (5-HT) in anxiety, we checked for strain differences regarding several determinants of 5-HT activity. In addition to confirming that LEW rats displayed anxious behaviors in the plus-maze compared with SHR, we found that in vitro, central tryptophan hydroxylase activity was higher in LEW rats than in SHR. However, ex vivo studies in midbrains and hippocampi revealed that neither 5-HT synthesis nor 5-HT and 5-hydroxyindoleacetic acid levels differed between strains. [3H]8-Hydroxy-2-(di-n-pro-pylamino)tetralin binding at midbrain 5-HT1A autoreceptors and hippocampal 5-HT1A postsynaptic receptors, [3H]ketanserin binding at cortical and striatal 5-HT2A receptors and [3H]citalopram binding at midbrain and hippocampal 5-HT transporters did not vary between strains. The inhibition of 5-HT synthesis by 5-HT1A autoreceptor stimulation was similar in both strains. Forepaw treading and flat body posture after 5-HT1A postsynaptic receptor stimulation were higher and lower, respectively, in SHR than in LEW rats. Last, 1-(4-iodo-2,5-dimethoxy-phenyl)-2-aminopropane- and quipazine-elicited head shakes, a 5-HT2A receptor-mediated response, were increased in the SHR strain compared with the LEW strain; on the other hand, 1-(3-chlorophenyl)piperazine triggered similar 5-HT2B/2C receptor-mediated decreases in motor activity in the two strains. This study shows that although the low-anxiety (SHR) and high-anxiety (LEW) strains vary in some aspects of 5-HT function, key components such as the 5-HT1A autoreceptors are not different.

  15. Mechanistic Investigation into the Decarboxylation of Aromatic Carboxylic Acids

    SciTech Connect

    Britt, P F; Buchanan, III, A C; Eskay, T P; Mungall, W S

    1999-08-22

    It has been proposed that carboxylic acids and carboxylates are major contributors to cross-linking reactions in low-rank coals and inhibit its thermochemical processing. Therefore, the thermolysis of aromatic carboxylic acids was investigated to determine the mechanisms of decarboxylation at temperatures relevant to coal processing, and to determine if decarboxylation leads to cross-linking (i.e., formation of more refractory products). From the thcrmolysis of simple and polymeric coal model compounds containing aromatic carboxylic acids at 250-425 °C, decarboxylation was found to occur primarily by an acid promoted ionic pathway. Carboxylate salts were found to enhance the decarboxylation rate, which is consistent with the proposed cationic mechanism. Thermolysis of the acid in an aromatic solvent, such as naphthalene, produced a small amount of arylated products (~5 mol%)), which constitute a low-temperature cross-link. These arylated products were formed by the rapid decomposition of aromatic anhydrides, which are in equilibrium with the acid. These anhydrides decompose by a free radical induced decomposition pathway to form atyl radicals that can add to aromatic rings to form cross-links or abstract hydrogen. Large amounts of CO were formed in the thennolysis of the anhydrides which is consistent with the induced decomposition pathway. CO was also formed in the thermolysis of the carboxylic acids in aromatic solvents which is consistent with the formation and decomposition of the anhydride. The formation of anhydride linkages and cross-links was found to be very sensitive to the reactions conditions. Hydrogen donor solvents, such as tetralin, and water were found to decrease the formation of arylated products. Silar reaction pathways were also found in the thermolysis of a polymeric model that contained aromatic carboxylic acids. In this case, anhydride formation and decomposition produced an insoluble polymer, while the O-methylated polymer and the non

  16. Low severity coal liquefaction promoted by cyclic olefins. Quarterly report, April--June 1993

    SciTech Connect

    Curtis, C.W.

    1993-11-01

    Low-severity coal liquefaction allows for the solubilization of coal with reduced gas make. The idea being tested in this research is whether selective bond rupture occurs during liquefaction at low temperatures that can be satisfied by hydrogen donation from highly active hydrogen donor compounds. Promotion of coal solubilization through hydrogen transfer using highly active and effective hydrogen donors is the objective of this study. The highly effective hydrogen donors being tested are cyclic olefins. Representative cyclic olefins are isotetralin (ISO), which is 1,4,5,8-tetrahydronaphthalene, and 1,4,5,8,9,10-hexahydroanthracene (HHA). These compounds have been shown to highly effective donors (Bedell and Curtis, 1991) which release their hydrogen at fairly low temperatures, in the 200 to 300{degree}C range. ISO has been shown to be much more effective than its hydroaromatic analogue tetralin (TET) in releasing hydrogen at low temperatures and transferring that hydrogen to an acceptor molecule or to coal (Bedell and Curtis, 1991). Likewise, at 380{degree}C, the ability of HHA to release hydrogen in both N{sub 2} and H{sub 2} atmospheres was greater than a comparative hydroaromatic compound, dihydroanthracene (DHA). However, when an acceptor molecule or coal was present, DHA was as or more active than HHA in transferring hydrogen (Bedell et al., 1993). In another study, at equivalent reaction conditions and in the presence of anthracene (ANT) as a hydrogen acceptor, ISO released more than 200 times as much hydrogen as TET and HHM released 18 to 25 times as much hydrogen as DHA (Wang, 1992).

  17. Coprocessing through fundamental and mechanistic studies in hydrogen transfer and catalysis. Quarterly report, September 26, 1991--December 26, 1991

    SciTech Connect

    Curtis, C.W.

    1991-12-31

    The research conducted during this quarter evaluated hydrogen transfer from hydroaromatics and cyclic olefins to aromatics under thermal and catalytic conditions. The reactions under study involved thermal reactions of a cyclic olefin, isotetralin (ISO), with aromatics, anthracene (ANT) and pyrene (PYR). These reactions completed a set of experiments with hydrogen-rich species and aromatics previously reported that included cycloalkanes of perhydropyrene (PHP) and perhydroanthracene (PHA), hydroaromatic donors, tetralin (TET) and dihydroanthracene (DHA), cyclic olefins, hexahydroanthracene (HHA) and ISO, and aromatics, PYR and ANT. Catalytic reactions performed this quarter used a sulfur catalyst that had been shown by Rudnick to affect the hydrogen transfer from cycloalkanes to aromatics and/or coal. Rudnick investigated the dehydrogenation of alicyclic compounds converting them to the corresponding aromatic compounds in a process in which the alicyclic compounds served as hydrogen donors. Thiophenol and thiol were effective catalysts and helped promote the conversion of alicyclic compounds to aromatic compounds. The research performed in our laboratory focused on evaluating the effect of a sulfur catalyst on the transfer of hydrogen from cycloalkanes like perhydropyrene (PHP) to aromatics like anthracene under catalytic conditions. The catalyst used in this study was sulfur generated from thiophenol present at a concentration level of 2000 ppm of sulfur. The reactions were performed under two temperature conditions, 380 and 440{degrees}C; both thermal and catalytic reactions were performed for comparison. In addition, the individual cycloalkane and aromatic compounds were reacted under these conditions so that a direct comparison of the effect of temperature and of catalyst on the reaction products formed could be made.

  18. Signalling properties and pharmacology of a 5-HT7 -type serotonin receptor from Tribolium castaneum.

    PubMed

    Vleugels, R; Lenaerts, C; Vanden Broeck, J; Verlinden, H

    2014-04-01

    In the last decade, genome sequence data and gene structure information on invertebrate receptors has been greatly expanded by large sequencing projects and cloning studies. This information is of great value for the identification of receptors; however, functional and pharmacological data are necessary for an accurate receptor classification and for practical applications. In insects, an important group of neurotransmitter and neurohormone receptors, for which ample sequence information is available but pharmacological information is missing, are the biogenic amine G protein-coupled receptors (GPCRs). In the present study, we investigated the sequence information, pharmacology and signalling properties of a 5-HT7 -type serotonin receptor from the red flour beetle, Tribolium castaneum (Trica5-HT7 ). The receptor encoding cDNA shows considerable sequence similarity with cognate 5-HT7 receptors and phylogenetic analysis also clusters the receptor within this 5-HT receptor group. Real-time reverse transcription PCR demonstrated high expression levels in the brain, indicating the possible importance of this receptor in neural processes. Trica5-HT7 was dose-dependently activated by 5-HT, which induced elevated intracellular cyclic AMP levels but had no effect on calcium signalling. The synthetic agonists, α-methyl 5-HT, 5-methoxytryptamine, 5-carboxamidotryptamine and 8-hydroxy-2-(dipropylamino)tetralin hydrobromide, showed a response, although with a much lower potency and efficacy than 5-HT. Ketanserin and methiothepin were the most potent antagonists. Both showed characteristics of competitive inhibition on Trica5-HT7 . The signalling pathway and pharmacological profile offer important information that will facilitate functional and comparative studies of 5-HT receptors in insects and other invertebrates. The pharmacology of invertebrate 5-HT receptors differs considerably from that of vertebrates. The present study may therefore contribute to establishing a more

  19. The role of 5-HT7 receptor antagonism in the amelioration of MK-801-induced learning and memory deficits by the novel atypical antipsychotic drug lurasidone.

    PubMed

    Horisawa, Tomoko; Nishikawa, Hiroyuki; Toma, Satoko; Ikeda, Atsushi; Horiguchi, Masakuni; Ono, Michiko; Ishiyama, Takeo; Taiji, Mutsuo

    2013-05-01

    Lurasidone is a novel atypical antipsychotic with high affinity for dopamine D2, serotonin 5-HT7 and 5-HT2A receptors. We previously reported that lurasidone and the selective 5-HT7 receptor antagonist, SB-656104-A improved learning and memory deficits induced by MK-801, an N-methyl-d-aspartate (NMDA) receptor antagonist, in the rat passive avoidance test. In this study, we first examined the role of the 5-HT7 receptor antagonistic activity of lurasidone in its pro-cognitive effect to ameliorate MK-801-induced deficits in the rat passive avoidance test. The 5-HT7 receptor agonist, AS19, (2S)-(+)-5-(1,3,5-trimethylpyrazol-4-yl)-2-(dimethylamino) tetralin, (3 mg/kg, s.c.) completely blocked the attenuating effects of lurasidone (3 mg/kg, p.o.), highlighting the importance of 5-HT7 receptor antagonism in the pro-cognitive effect of lurasidone. AS19 (3 mg/kg, s.c.) also blocked the ameliorating effect of SB-656104-A (10 mg/kg, i.p.) in the same experimental paradigm. To further extend our observation, we next tested whether 5-HT7 receptor antagonism still led to the amelioration of MK-801-induced deficits when combined with D2 and 5-HT2A receptor antagonists, and found that SB-656104-A (10 mg/kg, i.p.) significantly ameliorated MK-801-induced deficits even in the presence of the D2 receptor antagonist raclopride (0.1 mg/kg, s.c.) and 5-HT2A receptor antagonist ketanserin (1 mg/kg, s.c.). Taken together, these results suggest that the 5-HT7 receptor antagonistic activity of lurasidone plays an important role in its effectiveness against MK-801-induced deficits, and may contribute to its pharmacological actions in patients with schizophrenia.

  20. The role of endothelium-derived hyperpolarizing factor and cyclooxygenase pathways in the inhibitory serotonergic response to the pressor effect elicited by sympathetic stimulation in chronic sarpogrelate treated rats.

    PubMed

    García-Pedraza, José Ángel; García, Mónica; Martín, María Luisa; San Román, Luis; Morán, Asunción

    2014-05-15

    We have demonstrated that the antagonism of 5-HT2 receptors produces an enhancement of serotonergic sympathoinhibitory effect by 5-HT1D and 5-HT7 activation. The aim of this work was to determine mechanisms involved in the 5-hydroxytriptaminergic inhibitory action on the pressor responses elicited by sympathostimulation in pithed rats treated with a 5-HT2 receptor blocker. The blockade of 5-HT2 receptors was induced by orally sarpogrelate treatment (30 mg/kg/day). Two weeks later, animals were anaesthetized and pithed. A bolus injection of 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) (10 µg/kg), a guanylyl cyclase inhibitor, or indomethacin (2mg/kg), a non-selective COX inhibitor, prior to the infusion of (2S)(+)-5-(1,3,5-trimethylpyrazol-4-yl)-2-(dimethylamino)tetralin, AS-19 (5 µg/kg/min) were not able to abolish its inhibitory action. However, i.v. administration of glibenclamide (20mg/kg), a blocker of ATP-sensitive K(+) channels, completely reversed AS-19 sympathoinhibitory action. The inhibitory effect of 2-[5-[3-(4-methylsulfonylamino)benzyl-1,2,4-oxadiazol-5-yl]-1H-indol-3-yl]ethanamine, L-694,247 (5 µg/kg/min) was abolished by indomethacin, whereas pretreatment with ODQ had no effect. Nimesulide (3mg/kg), a COX-2 inhibitor, completely reversed the inhibitory action of L-694,247, whereas 1-[[4,5-bis (4-methoxyphenyl)-2-thiazolyl]carbonyl]-4-methylpiperazine hydrochloride (FR122047) (3mg/kg), a COX-1 inhibitor, partially blocked this action. The sympathoinhibition by 5-HT (20 µg/kg/min) could not be elicited after i.v. treatment with indomethacin plus glibenclamide. In conclusion, these results suggest that in chronic sarpogrelate-treated rats, the inhibitory serotonergic effect of the pressor responses induced by electrical stimulation of the sympathetic outflow via 5-HT7 and 5-HT1D receptor activation is mediated by KATP channel-mediated smooth muscle hyperpolarization and the COX pathway, respectively.

  1. Structure investigation of sertraline drug and its iodine product using mass spectrometry, thermal analyses and MO-calculations

    NASA Astrophysics Data System (ADS)

    Zayed, M. A.; Hawash, M. F.; Fahmey, M. A.; El-Habeeb, Abeer A.

    2007-11-01

    Sertraline (C 17H 17Cl 2N) as an antidepressant drug was investigated using thermal analysis (TA) measurements (TG/DTG and DTA) in comparison with electron impact (EI) mass spectral (MS) fragmentation at 70 eV. Semi-empirical MO-calculations, using PM3 procedure, has been carried out on neutral molecule and positively charged species. These calculations included bond length, bond order, bond strain, partial charge distribution and heats of formation (Δ Hf). Also, in the present work sertraline-iodine product was prepared and its structure was investigated using elemental analyses, IR, 1H NMR, 13C NMR, MS and TA. It was also subjected to molecular orbital calculations (MOC) in order to confirm its fragmentation behavior by both MS and TA in comparison with the sertraline parent drug. In MS of sertraline the initial rupture occurred was CH 3NH 2+ fragment ion via H-rearrangement while in sertraline-iodine product the initial rupture was due to the loss of I + and/or HI + fragment ions followed by CH 2dbnd NH + fragment ion loss. In thermal analyses (TA) the initial rupture in sertraline is due to the loss of C 6H 3Cl 2 followed by the loss of CH 3-NH forming tetraline molecule which thermally decomposed to give C 4H 8, C 6H 6 or the loss of H 2 forming naphthalene molecule which thermally sublimated. In sertraline-iodine product as a daughter the initial thermal rupture is due to successive loss of HI and CH 3NH followed by the loss of C 6H 5HI and HCl. Sertraline biological activity increases with the introduction of iodine into its skeleton. The activities of the drug and its daughter are mainly depend upon their fragmentation to give their metabolites in vivo systems, which are very similar to the identified fragments in both MS and TA. The importance of the present work is also due to the decision of the possible mechanism of fragmentation of the drug and its daughter and its confirmation by MOC.

  2. Recent Progress in the Development of Diesel Surrogate Fuels

    SciTech Connect

    Pitz, W J; Mueller, C J

    2009-12-09

    There has been much recent progress in the area of surrogate fuels for diesel. In the last few years, experiments and modeling have been performed on higher molecular weight components of relevance to diesel fuel such as n-hexadecane (n-cetane) and 2,2,4,4,6,8,8-heptamethylnonane (iso-cetane). Chemical kinetic models have been developed for all the n-alkanes up to 16 carbon atoms. Also, there has been much experimental and modeling work on lower molecular weight surrogate components such as n-decane and n-dodecane that are most relevant to jet fuel surrogates, but are also relevant to diesel surrogates where simulation of the full boiling point range is desired. For two-ring compounds, experimental work on decalin and tetralin recently has been published. For multi-component surrogate fuel mixtures, recent work on modeling of these mixtures and comparisons to real diesel fuel is reviewed. Detailed chemical kinetic models for surrogate fuels are very large in size. Significant progress also has been made in improving the mechanism reduction tools that are needed to make these large models practicable in multi-dimensional reacting flow simulations of diesel combustion. Nevertheless, major research gaps remain. In the case of iso-alkanes, there are experiments and modeling work on only one of relevance to diesel: iso-cetane. Also, the iso-alkanes in diesel are lightly branched and no detailed chemical kinetic models or experimental investigations are available for such compounds. More components are needed to fill out the iso-alkane boiling point range. For the aromatic class of compounds, there has been no new work for compounds in the boiling point range of diesel. Most of the new work has been on alkyl aromatics that are of the range C7 to C8, below the C10 to C20 range that is needed. For the chemical class of cycloalkanes, experiments and modeling on higher molecular weight components are warranted. Finally for multi-component surrogates needed to treat real

  3. Podophyllum hexandrum as a potential botanical supplement for the medical management of nuclear and radiological emergencies (NREs) and free radical-mediated ailments: leads from in vitro/in vivo radioprotective efficacy evaluation.

    PubMed

    Arora, Rajesh; Chawla, Raman; Dhaker, Atlar Singh; Adhikari, Manish; Sharma, Jyoti; Singh, Shikha; Gupta, Damodar; Kumar, Raj; Sharma, Ashok; Sharma, Rakesh K; Tripathi, Rajender P

    2010-03-01

    Management of radiation-induced reactive oxygen/nitrogen species requires a holistic approach to mitigate the deleterious effects of free radicals. Flora of the Himalayas, which prevails under extreme climatic conditions, has been explored for its potential utility to develop radioprotective drugs. The Himalayan high altitude medicinal plant, Podophyllum hexandrum Royle, was selected on the basis of its unique properties, and a novel fractionated nonpolar extract (REC-2003) was prepared and evaluated for radioprotective efficacy, in vitro as well as in vivo. The free radical scavenging activity of REC-2003 was found to be > 75% (20 μg/ml) with maximum superoxide scavenging activity (57.56 ± 1.38%) recorded at 1 mg/ml concentration (tetrazolium-based estimation). More than 30% inhibition of nitric oxide radicals was observed at concentrations > 0.5 mg/ml, while hydroxyl radical scavenging activity (deoxy-D-ribose assay) exhibited a dose-dependent (100-600 μg/ml) increase. Significantly high (90%) protection to human erythrocytes was observed at 75 μg/ml, which was found to be the most optimized dose. Similarly, more than 90% inhibition was observed against lipid peroxidation (evaluated by estimating levels of malondialdehyde). The significant antihemolytic potential of REC-2003 could be attributed to its ability to scavenge free radicals, reduce peroxidative stress on lipid membranes, and render protection to DNA (evaluated using plasmid relaxation assay). All these activities holistically contributed toward the radioprotective ability. REC-2003 (8 mg/kg BW; intraperitoneal (i.p.), -30 min) rendered > 80% total-body protection in Swiss Albino Strain 'A' mice [against lethal radiation (10 Gy)] in a 30-day survival assay. Phytochemical characterization of the constituents of REC-2003 revealed the presence of polyphenolics (flavonoids). The characterized constituents also included the aryl-tetralin lignans like podophyllotoxin, its glycoside, 4'-demethyl derivative

  4. Recent Progress in the Development of Diesel Surrogate Fuels

    SciTech Connect

    Pitz, W J

    2009-09-04

    There has been much recent progress in the area of surrogate fuels for diesel. In the last few years, experiments and modeling have been performed on higher molecular weight components of relevance to diesel fuel such as n-hexadecane (n-cetane) and 2,2,4,4,6,8,8-heptamethylnonane (iso-cetane). Chemical kinetic models have been developed for all the n-alkanes up to 16 carbon atoms. Also, there has been much experimental and modeling work on lower molecular weight surrogate components such as n-decane and do-decane which are most relevant to jet fuel surrogates, but are also relevant to diesel surrogates where simulation of the full boiling point range is desired. For the cycloalkanes, experimental work on decalin and tetralin recently has been published. For multi-component surrogate fuel mixtures, recent work on modeling of these mixtures and comparisons to real diesel fuel is reviewed. Detailed chemical kinetic models for surrogate fuels are very large in size. Significant progress also has been made in improving the mechanism reduction tools that are needed to make these large models practicable in multidimensional reacting flow simulations of diesel combustion. Nevertheless, major research gaps remain. In the case of iso-alkanes, there are experiments and modeling work on only one of relevance to diesel: iso-cetane. Also, the iso-alkanes in diesel are lightly branched and no detailed chemical kinetic models or experimental investigations are available for such compounds. More components are needed to fill out the iso-alkane boiling point range. For the aromatic class of compounds, there has been no new work for compounds in the boiling point range of diesel. Most of the new work has been on alkyl aromatics that are of the range C7 to C8, below the C10 to C20 range that is needed. For the chemical class of cycloalkanes, experiments and modeling on higher molecular weight components are warranted. Finally for multi-component surrogates needed to treat real diesel

  5. Vanadium(iv and v) complexes of pyrazolone based ligands: Synthesis, structural characterization and catalytic applications.

    PubMed

    Maurya, Mannar R; Sarkar, Bithika; Avecilla, Fernando; Correia, Isabel

    2016-11-01

    The ONO donor ligands obtained from the condensation of 4-benzoyl-3-methyl-1-phenyl-2-pyrazoline-5-one (Hbp) with benzoylhydrazide (H2bp-bhz I), furoylhydrazide (H2bp-fah II), nicotinoylhydrazide (H2bp-nah III) and isonicotinoylhydrazide (H2bp-inh IV), upon treatment with [V(IV)O(acac)2], lead to the formation of [V(IV)O(bp-bhz)(H2O)] 1, [V(IV)O(bp-fah)(H2O)] 2, [V(IV)O(bp-nah)(H2O)] 3 and [V(IV)O(bp-inh)(H2O)] 4, respectively. At neutral pH the in situ generated aqueous K[H2V(V)O4] reacts with ligands I and II, forming potassium salts, K(H2O)2[V(V)O2(bp-bhz)] 5 and K(H2O)2[V(V)O2(bp-fah)] 6, while ligands III and IV give neutral complexes, [V(V)O2(Hbp-nah)] 9 and [V(V)O2(Hbp-inh)] 10, respectively. Acidification of aqueous solutions of 5 and 6 with HCl also gives neutral complexes [V(V)O2(Hbp-bhz)] 7 and [V(V)O2(Hbp-fah)] 8, respectively. Complexes 1-4, upon slow aerial oxidation in methanol, convert into monooxidovanadium(v) complexes, [V(V)O(bp-bhz)(OMe)] 11, [V(V)O(bp-fah)(OMe)] 12, [V(V)O(bp-nah)(OMe)] 13 and [V(V)O(bp-inh)(OMe)] 14, respectively. All complexes were characterized by various spectroscopic techniques like FT-IR, UV-visible, EPR (for complexes 1-4) and NMR ((1)H, (13)C and (51)V), elemental analysis, thermogravimetry and single crystal X-ray diffraction (for complexes 5-10 and 12). In the solid state, all complexes characterized by X-ray diffraction show the metal ion 5-coordinated in a distorted square pyramidal geometry. Complexes 11-14 were tested as catalysts for the one-pot three-component (ethylacetoacetate, benzaldehyde and ammonium acetate) dynamic covalent assembly, via Hantzsch reaction, using hydrogen peroxide as oxidant in solution and under solvent-free conditions. The complexes are also active catalysts for the oxidation of tetralin to tetralone with H2O2 as oxidant. The influence of the amounts of catalyst and oxidant, and solvent, temperature and time on the catalyzed reactions was investigated.

  6. C1 Chemistry for the Production of Ultra-Clean Liquid Transportation Fuels and Hydrogen

    SciTech Connect

    Gerald P. Huffman

    2006-03-30

    -M (M=Ni, Mo, Pd) catalysts exhibit excellent activity for dehydrogenation of gaseous alkanes, yielding pure hydrogen and carbon nanotubes in one reaction. A fluidized-bed/fixed-bed methane reactor was developed for continuous hydrogen and nanotube production. (6) A process for co-production of hydrogen and methyl formate from methanol has been developed. (7) Pt nanoparticles on stacked-cone carbon nanotubes easily strip hydrogen from liquids such as cyclohexane, methylcyclohexane, tetralin and decalin, leaving rechargeable aromatic phases. (8) Hydrogen volume percentages produced during reforming of methanol in supercritical water in the output stream are {approx}98%, while CO and CO2 percentages are <2 %.

  7. Refinery Integration of By-Products from Coal-Derived Jet Fuels

    SciTech Connect

    Caroline Clifford; Andre Boehman; Chunshan Song; Bruce Miller; Gareth Mitchell

    2008-03-31

    fuels ({approx}60 ON for coal-based gasoline and {approx}20 CN for coal-based diesel fuel). Therefore, the allowable range of blending levels was studied where the blend would achieve acceptable performance. However, in both cases of the coal-based fuels, their ignition characteristics may make them ideal fuels for advanced combustion strategies where lower ON and CN are desirable. Task 3 was designed to develop new approaches for producing ultra clean fuels and value-added chemicals from refinery streams involving coal as a part of the feedstock. It consisted of the following three parts: (1) desulfurization and denitrogenation which involves both new adsorption approach for selective removal of nitrogen and sulfur and new catalysts for more effective hydrotreating and the combination of adsorption denitrogenation with hydrodesulfurization; (2) saturation of two-ring aromatics that included new design of sulfur resistant noble-metal catalysts for hydrogenation of naphthalene and tetralin in middle distillate fuels, and (3) value-added chemicals from naphthalene and biphenyl, which aimed at developing value-added organic chemicals from refinery streams such as 2,6-dimethylnaphthalene and 4,4{prime}-dimethylbiphenyl as precursors to advanced polymer materials. Major advances were achieved in this project in designing the catalysts and sorbent materials, and in developing fundamental understanding. The objective of Task 4 was to evaluate the effect of introducing coal into an existing petroleum refinery on the fuel oil product, specifically trace element emissions. Activities performed to accomplish this objective included analyzing two petroleum-based commercial heavy fuel oils (i.e., No. 6 fuel oils) as baseline fuels and three co-processed fuel oils, characterizing the atomization performance of a No. 6 fuel oil, measuring the combustion performance and emissions of the five fuels, specifically major, minor, and trace elements when fired in a watertube boiler designed