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Sample records for naloxone-precipitated withdrawal signs

  1. Suppressive effects of rosa damascena essential oil on naloxone- precipitated morphine withdrawal signs in male mice.

    PubMed

    Abbasi Maleki, Navid; Abbasi Maleki, Saeid; Bekhradi, Reza

    2013-01-01

    This research was done to test the effect of Rosa damascena essential oil on withdrawal signs of naloxone-precipitated morphine in male mice. Morphine dependence was induced by injection (IP) three times daily at doses of 50, 50 and 75 mg/kg, respectively, for 3 days. On day 4, after the last administration of morphine, Rosa damascena essential oil was administered at different concentrations (5, 2 and 40%, IP) 30 min before administration of naloxone (5 mg/kg, IP). The following actions were taken as signs of withdrawal and records taken for jumping as a number and scores of 0 to 3 were given for incidences of grooming, teeth chattering, rearing, writing, diarrhea, wet dog shakes and climbing during a 30 min period. Results showed that different concentrations of Rosa damascena essential oil significantly reduced signs of morphine withdrawal compared to the control group in terms of number of jumps (p < 0.05 and p < 0.01), grooming, teeth chattering, rearing, climbing, wet dog shakes and writhing, but not for diarrhea (p < 0.05). In conclusion it seems that GABAergic activity induced by flavonoids from Rosa damascena essential oil can alleviate signs of morphine withdrawal, but further studies need to be done to better understand this mechanism. PMID:24250642

  2. Primary sensory neurones and naloxone-precipitated morphine withdrawal.

    PubMed Central

    Donnerer, J.

    1989-01-01

    1. The C-fibre-evoked depressor reflex following i.a. injection of capsaicin and the wiping movements following chemical irritation of the cornea by capsaicin were both found to be augmented in the naloxone-precipitated morphine withdrawal phase. 2. The in vitro capsaicin-evoked release of substance P from central terminals of C-fibre afferents in the spinal cord was decreased in morphine-treated rats. Following naloxone, the release in the morphine-treated group was as large as in the control group. 3. The C-fibre mediated plasma extravasation in the rat paw after naloxone was found to be the same in morphine-treated and control rats. 4. It is concluded that C-fibre-evoked reflex reactions are augmented during morphine withdrawal, but that the mechanisms responsible are either located postsynaptically to the primary sensory neurone or further centrally. PMID:2472843

  3. Role of calcium in morphine dependence and naloxone-precipitated withdrawal in mice

    PubMed Central

    Seth, Vikas; Upadhyaya, Prerna; Moghe, Vijay; Ahmad, Mushtaq

    2011-01-01

    Purpose To explore the role of calcium in morphine withdrawal syndrome using various agents affecting calcium levels in cytoplasm. Methods Mice were rendered dependent on morphine by subcutaneous injection of morphine, and withdrawal was induced 4 hours later by injecting the opioid antagonist, naloxone. Mice were observed for 30 minutes for signs of withdrawal, ie, characteristic jumping, hyperactivity, urination, and diarrhea. Various calcium channel blockers were injected intraperitoneally 30 minutes before naloxone to evaluate their influence on the severity of the withdrawal syndrome. We also tested the effect of combination levodopa-carbidopa pretreatment and its interaction with a selective alpha-1 blocker, terazosin, on naloxone-precipitated withdrawal in mice acutely dependent on morphine. Results A significant dose-dependent attenuation of naloxone-induced morphine withdrawal syndrome was observed with calcium channel blockers, ie, verapamil 20 mg/kg (P < 0.05) and diltiazem 30 mg/kg (P < 0.01). Combination levodopa-carbidopa pretreatment facilitated the morphine withdrawal syndrome, and this was found to be blocked by terazosin, although not to a statistically significant (P > 0.05) extent. Conclusion The results indicate that calcium plays an important role in the genesis of morphine dependence and withdrawal, and suggest the usefulness of calcium channel blockers in the management of morphine withdrawal syndrome.

  4. Dopamine D2 receptor availability in opiate addicts at baseline and during naloxone precipitated withdrawal

    SciTech Connect

    Wang, G.J.; Volkow, N.D.; Logan, J. ||

    1996-05-01

    To determine if changes in dopamine activity contribute to the clinical presentation of opiate withdrawal we assessed dopamine (DA) D2 receptor availability in opiate-dependent subjects at baseline and during naloxone-precipitated withdrawal. DA D2 receptor availability was evaluated in eleven male heroine and methadone users using positron emission tomography (PET) and [11-C]raclopride and compared to eleven age matched male control subjects. Nine of the opiate-dependent subjects and two of the control were tested twice after placebo and naloxone (0.02 mg/kg) iv injection 7-10 min. prior to [11-C]raclopride. DA D2 receptor availability was measured using the ratio of the distribution volume in the region of interest (caudate, putamen and ventral striatum) to that in the cerebellum which is a function of B{sub max}/K{sub d}. DA D2 receptor availability in putamen was significantly lower in opiate-dependent subjects (3.44 {plus_minus} 0.4) than that in controls (3.97 {plus_minus} 0.45, p {ge} 0.009). Naloxone induced a short lasting withdrawal in all of the opiate-dependent subjects (79 {plus_minus} 17% of maximum withdrawal), but not in controls, with significant increase in pulse (p {le} 0.006), blood pressure (p {le} 0.0001), lacrimation (p {le} 0.01), muscle twitches (p {le} 0.01), annoyance (p {le} 0.005), anxiety (p {le} 0.0006), restlessness (p {le} 0.0005) and unhappiness (p {le} 0.001). DA D2 receptor availability in basal ganglia after naloxone administration was not different from that of baseline. These results document abnormalities in DA D2 receptors in opiate-dependent subjects. However, DA D2 availability did not change with naloxone-precipitated withdrawal.

  5. Naloxone-precipitated morphine withdrawal increases pontine glutamate levels in the rat.

    PubMed

    Zhang, T; Feng, Y; Rockhold, R W; Ho, I K

    1994-01-01

    Extracellular fluid (ECF) levels of glutamate (Glu) and aspartate (Asp) were measured in the locus coeruleus (LC) during morphine withdrawal by using microdialysis in conscious morphine-dependent Sprague-Dawley rats. Guide cannulae were implanted chronically and rats were given intracerebroventricular (i.c.v.) infusions of morphine (26 nmol/1 microliters/hr) or saline (1 microliters/hr) for 3 days. Microdialysis probes (2 mm tip) were inserted into the LC 24 hr before precipitation of withdrawal by i.c.v. injection of naloxone (12 or 48 nmol/5 microliters). Behavioral evidence of withdrawal (teeth-chattering, wet-dog shakes, etc.) was detected following naloxone challenge in morphine, but not in saline-infused rats. Increases (P < 0.01) in ECF levels of Glu (and Asp, to a lesser degree) were noted after naloxone-precipitated withdrawal only in the morphine group. The ECF Glu levels in the LC increased from 9.6 +/- 2.7 to 15.5 +/- 5.0 microM following 12 nmol/5 microliters naloxone, and from 9.5 +/- 1.9 to 20.5 +/- 3.3 microM following 48 nmol/5 microliters naloxone, before and in the first 15 min sample after the precipitation of withdrawal in the morphine-dependent rats, respectively. These results provide direct evidence to support the role of excitatory amino acids within the LC in morphine withdrawal. PMID:7912397

  6. Cardiac adverse effects of naloxone-precipitated morphine withdrawal on right ventricle: Role of corticotropin-releasing factor (CRF) 1 receptor

    SciTech Connect

    Navarro-Zaragoza, J.; Martínez-Laorden, E.; Mora, L.; Hidalgo, J.; Milanés, M.V.; Laorden, M.L.

    2014-02-15

    Opioid addiction is associated with cardiovascular disease. However, mechanisms linking opioid addiction and cardiovascular disease remain unclear. This study investigated the role of corticotropin-releasing factor (CRF) 1 receptor in mediating somatic signs and the behavioural states produced during withdrawal from morphine dependence. Furthermore, it studied the efficacy of CRF1 receptor antagonist, CP-154,526 to prevent the cardiac sympathetic activity induced by morphine withdrawal. In addition, tyrosine hydroxylase (TH) phosphorylation pathways were evaluated. Like stress, morphine withdrawal induced an increase in the hypothalamic–pituitary–adrenal (HPA) axis activity and an enhancement of noradrenaline (NA) turnover. Pre-treatment with CRF1 receptor antagonist significantly reduced morphine withdrawal-induced increases in plasma adrenocorticotropic hormone (ACTH) levels, NA turnover and TH phosphorylation at Ser31 in the right ventricle. In addition, CP-154,526 reduced the phosphorylation of extracellular signal-regulated kinase (ERK) after naloxone-precipitated morphine withdrawal. In addition, CP-154,526 attenuated the increases in body weight loss during morphine treatment and suppressed some of morphine withdrawal signs. Altogether, these results support the idea that cardiac sympathetic pathways are activated in response to naloxone-precipitated morphine withdrawal suggesting that treatment with a CRF1 receptor antagonist before morphine withdrawal would prevent the development of stress-induced behavioural and autonomic dysfunction in opioid addicts. - Highlights: • Morphine withdrawal caused an increase in myocardial sympathetic activity. • ERK regulates TH phosphorylation after naloxone-induced morphine withdrawal. • CRF1R is involved in cardiac adaptive changes during morphine dependence.

  7. CB1 antagonism: interference with affective properties of acute naloxone-precipitated morphine withdrawal in rats

    PubMed Central

    Wills, Kiri L.; Vemuri, Kiran; Kalmar, Alana; Lee, Alan; Limebeer, Cheryl L.; Makriyannis, Alexandros

    2014-01-01

    Rationale Modulation of the endocannabinoid system has been found to interfere with opiate withdrawal. The potential of activation and blockade of the endocannabinoid system to prevent the aversive-affective state of naloxone-precipitated morphine withdrawal (MWD) was investigated in a one-trial conditioned place aversion (CPA) paradigm. Objective CPA provides a sensitive measure of the motivational effects of acute MWD. The potential of the fatty acid amide hydrolase (FAAH) inhibitors, URB597 and PF-3845, the CB1 antagonist/inverse agonist, AM251, and the neutral CB1 antagonists, AM4113 and AM6527 (oral), to interfere with establishment of a MWD-induced CPA was investigated. As well, the potential of AM251 and AM4113 to interfere with reinstatement of a previously established MWD-induced CPA was investigated. Materials and methods Using a one-trial place conditioning paradigm, rats were administered naloxone (1 mg/kg, subcutaneous (sc)) 24 h after receiving a high dose of morphine (20 mg/kg, sc) and were placed on the conditioning floor. To determine the effect of each pretreatment drug on the establishment of the MWD-induced CPA, URB597 (0.3 mg/kg, intraperitoneally (ip)), PF-3845 (10 mg/kg, ip), AM251 (1 or 2.5 mg/kg, ip), AM4113 (1 or 2.5 mg/kg, ip), and AM6527 (5 mg/kg, oral) were administered prior to conditioning. Results AM251 (2.5, but not 1 mg/k), AM4113, and AM6527, but not URB597 or PF-3845, interfered with the establishment of the MWD-induced CPA. AM251 and AM4113 did not prevent reinstatement of the CPA. Conclusions Neutral antagonism of the CB1 receptor reduces the aversive affective properties of morphine withdrawal. PMID:24770676

  8. Suppression of naloxone-precipitated withdrawal jumps in morphine-dependent mice by stimulation of prostaglandin EP3 receptor.

    PubMed Central

    Nakagawa, T.; Minami, M.; Katsumata, S.; Ienaga, Y.; Satoh, M.

    1995-01-01

    1. We have shown that intracisternal (i.c.) administration of interleukin-1 beta (IL-1 beta) attenuates naloxone-precipitated withdrawal jumps in morphine-dependent mice, and the effect was partly mediated by the corticotropin-releasing factor. To elucidate further other possible mechanisms involved in the inhibitory effect of IL-1 beta on morphine withdrawal jumping behaviour, in this study, we examined the involvement of the prostaglandin-synthesis pathway, because prostaglandins have been shown to mediate the several central effects of IL-1. Furthermore, we examined the effects of subtype-selective prostaglandin receptor agonists on morphine withdrawal jumping behaviour. 2. Mice were rendered morphine-dependent by subcutaneous implantation of a pellet containing 11.5 +/- 0.3 mg morphine hydrochloride for 48 h. Morphine withdrawal syndromes were precipitated by intraperitoneal (i.p.) injection of naloxone (10 mg kg-1). The degree of physical dependence on morphine was estimated by counting the number of jumps, one of the typical withdrawal signs in mice, for 40 min. 3. The inhibitory effect of IL-1 beta (1 ng/mouse) administered intracisternally 30 min before naloxone (10 mg kg-1, i.p.) was significantly blocked by pretreatment with sodium salicylate (a cyclo-oxygenase inhibitor, 10 ng or 30 ng/mouse) administered intracisternally 15 min before IL-1 beta, while i.c. administration of sodium salicylate alone (3 ng, 10 ng or 30 ng/mouse) followed by i.c. administration of vehicle instead of IL-1 beta did not significantly change the number of jumps precipitated by naloxone. 4. Intracisternal administration of M&B28,767 (an EP3-receptor agonist, 1 fg-30 ng/mouse) and sulprostone (an EP1/EP3-receptor agonist, 10 fg-100 ng/mouse) 30 min before naloxone (10 mg kg,-1 i.p.) attenuated withdrawal jumps with a U-shaped dose-response, reaching a peak at 10 pg/mouse and 100 pg/mouse, respectively. On the other hand, i.c. administration of iloprost (an EP1/IP-receptor agonist

  9. Sympathetic activity induced by naloxone-precipitated morphine withdrawal is blocked in genetically engineered mice lacking functional CRF1 receptor

    SciTech Connect

    García-Carmona, Juan-Antonio; Martínez-Laorden, Elena; Milanés, María-Victoria; Laorden, María-Luisa

    2015-02-15

    There is large body evidence indicating that stress can lead to cardiovascular disease. However, the exact brain areas and the mechanisms involved remain to be revealed. Here, we performed a series of experiments to characterize the role of CRF1 receptor (CRF1R) in the stress response induced by naloxone-precipitated morphine withdrawal. The experiments were performed in the hypothalamic paraventricular nucleus (PVN) ventrolateral medulla (VLM), brain regions involved in the regulation of cardiovascular activity, and in the right ventricle by using genetically engineered mice lacking functional CRF1R levels (KO). Mice were treated with increasing doses of morphine and withdrawal was precipitated by naloxone administration. Noradrenaline (NA) turnover, c-Fos, expression, PKA and TH phosphorylated at serine 40, was evaluated by high-performance liquid chromatography (HPLC), immunohistochemistry and immunoblotting. Morphine withdrawal induced an enhancement of NA turnover in PVN in parallel with an increase in TH neurons expressing c-Fos in VLM in wild-type mice. In addition we have demonstrated an increase in NA turnover, TH phosphorylated at serine 40 and PKA levels in heart. The main finding of the present study was that NA turnover, TH positive neurons that express c-Fos, TH phosphorylated at serine 40 and PKA expression observed during morphine withdrawal were significantly inhibited in CRF1R KO mice. Our results demonstrate that CRF/CRF1R activation may contribute to the adaptive changes induced by naloxone-precipitated withdrawal in the heart and in the brain areas which modulate the cardiac sympathetic function and suggest that CRF/CRF1R pathways could be contributing to cardiovascular disease associated to opioid addiction. - Highlights: • Naloxone-precipitated morphine withdrawal increases sympathetic activity in the PVN and heart. • Co-localization of TH phosphorylated at serine 40/c-Fos in the VLM after morphine withdrawalNaloxone-precipitated

  10. Baclofen prevents the elevated plus maze behavior and BDNF expression during naloxone precipitated morphine withdrawal in male and female mice.

    PubMed

    Pedrón, Valeria T; Varani, André P; Balerio, Graciela N

    2016-05-01

    In previous studies we have shown that baclofen, a selective GABAB receptor agonist, prevents the somatic expression and reestablishes the dopamine and μ-opioid receptors levels, modified during naloxone-precipitated morphine withdrawal syndrome in male and female mice. There are no previous reports regarding sex differences in the elevated plus maze (EPM) and the expression of BDNF in morphine-withdrawn mice. The present study analyses the behavioral and biochemical variations during morphine withdrawal in mice of both sexes, and whether these variations are prevented with baclofen. Swiss-Webster albino prepubertal mice received morphine (2 mg/kg, i.p.) twice daily, for 9 consecutive days. On the 10th day, one group of morphine-treated mice received naloxone (opioid receptor antagonist; 6 mg/kg, i.p.) 1 h after the last dose of morphine to precipitate withdrawal. A second group received baclofen (2 mg/kg, i.p.) before naloxone administration. The EPM behavior was measured during 15 min after naloxone injection. The expression of BDNF-positive cells was determined by immunohistochemistry. Withdrawn male mice showed a higher percentage of time spent and number of entries to the open arms compared to withdrawn female mice. Baclofen prevented this behavior in both sexes. BDNF expression decreased in the AcbC, BNST, CeC, and CA3 of the hippocampus while increased in the BLA of morphine withdrawn male. Baclofen pretreatment prevented the BDNF expression observed in morphine withdrawn male mice in all the brain areas studied except in the CeC. Baclofen prevention of the EPM behavior associated to morphine withdrawal could be partially related to changes in BDNF expression. PMID:26789010

  11. Baclofen reestablishes striatal and cortical dopamine concentrations during naloxone-precipitated withdrawal.

    PubMed

    Diaz, Silvina L; Kemmling, Alma K; Balerio, Graciela N

    2003-03-01

    The present study analyzes the effects of baclofen (BAC) on mice brain neurochemical alterations during the morphine (MOR) withdrawal syndrome. Male Swiss-Webster albino mice (27-33 g) were rendered dependent by intraperitoneal (i.p.) injection of MOR (2mg/kg), twice daily for 9 days. On day 10, the dependent animals were divided into two groups: one receiving naloxone (NAL; 6 mg/kg i.p.) to precipitate the withdrawal syndrome 60 min after the last dose of MOR and the other received BAC (2mg/kg, i.p.) followed by NAL (6 mg/kg, i.p.), injected 30 and 60 min after the last dose of MOR, respectively. Ten minutes after these treatments, mice were killed by decapitation and the striatum, cortex and hippocampus were dissected to determine endogenous concentrations of dopamine (DA), 5-hydroxytryptamine (5-HT) and their metabolites using HPLC with electrochemical detection. Striatal DA, dihydroxyphenyl acetic acid (DOPAC) and homovanillic acid (HVA) concentrations as well as cortical DA concentrations of the withdrawal groups decreased significantly with respect to the control groups. BAC attenuated the decrease in DA and DOPAC concentrations observed during the withdrawal, without modifying per se the control DA concentrations. No changes on 5-HT and its metabolite 5-hydroxyindolacetic acid (5-HIAA) concentrations were observed during the MOR abstinence syndrome. The prevention caused by BAC on the decreased concentrations of DA induced by MOR withdrawal could have a therapeutic interest for the management of withdrawal syndrome. PMID:12470702

  12. Sublingual Buprenorphine/Naloxone Precipitated Withdrawal in Subjects Maintained on 100 mg of Daily Methadone*

    PubMed Central

    Rosado, James; Walsh, Sharon L.; Bigelow, George E.; Strain, Eric C.

    2007-01-01

    Rationale Acute doses of buprenorphine can precipitate withdrawal in opioid dependent persons. The likelihood of this withdrawal increases as a function of the level of physical dependence. Objectives To test the acute effects of sublingual buprenorphine/naloxone tablets in volunteers with a higher level of physical dependence. The goal was to identify a dose that would precipitate withdrawal (Phase 1), then determine if withdrawal could be attenuated by splitting this dose (Phase 2). Methods Residential laboratory study; subjects (N=16) maintained on 100 mg per day of methadone. Phase 1: Randomized, double blind, triple dummy, within subject study. Conditions were sublingual buprenorphine/naloxone (4/1, 8/2, 16/4, 32/8 mg), intramuscular naloxone (0.2 mg), oral methadone (100 mg), or placebo. Medication conditions were randomized, but buprenorphine/naloxone doses were ascending within the randomization. Phase 2: Conditions were methadone, placebo, naloxone, 100% of the buprenorphine/naloxone dose that precipitated withdrawal in Phase 1 (full dose), and 50% of this dose administered twice in a session (split dose). Analyses covaried by trough methadone serum levels. Results Six subjects did not complete the study. Of the ten who completed, three tolerated up to 32/8 mg of buprenorphine/naloxone without evidence of precipitated withdrawal. For the seven completing both phases, split doses generally produced less precipitated withdrawal compared to full doses. Conclusions There is considerable between subject variability in sensitivity to buprenorphine's antagonist effects. Low, repeated doses of buprenorphine/naloxone (e.g., 2/0.5 mg) may be an effective mechanism for safely dosing this medication in persons with higher levels of physical dependence. PMID:17517480

  13. Activation of serotonin 5-HT(2C) receptor suppresses behavioral sensitization and naloxone-precipitated withdrawal symptoms in heroin-treated mice.

    PubMed

    Wu, Xian; Pang, Gang; Zhang, Yong-Mei; Li, Guangwu; Xu, Shengchun; Dong, Liuyi; Stackman, Robert W; Zhang, Gongliang

    2015-10-21

    Abuse and dependence to heroin has evolved into a global epidemic as a significant clinical and societal problem with devastating consequences. Repeated exposure to heroin can induce long-lasting behavioral sensitization and withdrawal. Pharmacological activation of 5-HT2C receptors (5-HT2CRs) suppresses psychostimulant-induced drug-seeking and behavioral sensitization. The present study examined the effect of a selective 5-HT2CR agonist lorcaserin on behavioral sensitization and naloxone-precipitated withdrawal symptoms in heroin-treated mice. Male mice received heroin (1.0 mg/kg, s.c.) twice a day for 3 days and then drug treatment was suspended for 5 days. On day 9, a challenge dose of heroin (1.0 mg/kg) was administered to examine the expression of behavioral sensitization. Lorcaserin administered during the development, withdrawal or expression stage suppressed heroin-induced behavioral sensitization on day 9. Another cohort of mice received increasing doses of heroin over a 4.5-day period. Lorcaserin, or the positive control clonidine (an α2-adrenoceptor agonist) suppressed naloxone-precipitated withdrawal symptoms in heroin-treated mice. These findings suggest that activation of 5-HT2CRs suppresses behavioral sensitization and withdrawal in heroin-treated mice. Thus, pharmacological activation of 5-HT2CRs may represent a new avenue for the treatment of heroin addiction. PMID:26375926

  14. Activation of serotonin 5-HT(2C) receptor suppresses behavioral sensitization and naloxone-precipitated withdrawal symptoms in morphine-dependent mice.

    PubMed

    Zhang, Gongliang; Wu, Xian; Zhang, Yong-Mei; Liu, Huan; Jiang, Qin; Pang, Gang; Tao, Xinrong; Dong, Liuyi; Stackman, Robert W

    2016-02-01

    Opioid abuse and dependence have evolved into an international epidemic as a significant clinical and societal problem with devastating consequences. Repeated exposure to the opioid, for example morphine, can induce profound, long-lasting behavioral sensitization and physical dependence, which are thought to reflect neuroplasticity in neural circuitry. Central serotonin (5-HT) neurotransmission participates in the development of dependence on and the expression of withdrawal from morphine. Serotonin 5-HT(2C) receptor (5-HT(2C)R) agonists suppress psychostimulant nicotine or cocaine-induced behavioral sensitization and drug-seeking behavior; however, the impact of 5-HT(2C)R agonists on behaviors relevant to opioid abuse and dependence has not been reported. In the present study, the effects of 5-HT(2C)R activation on the behavioral sensitization and naloxone-precipitated withdrawal symptoms were examined in mice underwent repeated exposure to morphine. Male mice received morphine (10 mg/kg, s.c.) to develop behavioral sensitization. Lorcaserin, a 5-HT(2C)R agonist, prevented the induction and expression, but not the development, of morphine-induced behavioral sensitization. Another cohort of mice received increasing doses of morphine over a 7-day period to induce morphine-dependence. Pretreatment of lorcaserin, or the positive control clonidine (an alpha 2-adrenoceptor agonist), ameliorated the naloxone-precipitated withdrawal symptoms. SB 242084, a selective 5-HT(2C)R antagonist, prevented the lorcaserin-mediated suppression of behavioral sensitization and withdrawal. Chronic morphine treatment was associated with an increase in the expression of 5-HT(2C)R protein in the ventral tegmental area, locus coeruleus and nucleus accumbens. These findings suggest that 5-HT(2C)R can modulate behavioral sensitization and withdrawal in morphine-dependent mice, and the activation of 5-HT(2C)R may represent a new avenue for the treatment of opioid addiction. PMID:26432939

  15. Double Dissociation of Monoacylglycerol Lipase Inhibition and CB1 Antagonism in the Central Amygdala, Basolateral Amygdala, and the Interoceptive Insular Cortex on the Affective Properties of Acute Naloxone-Precipitated Morphine Withdrawal in Rats.

    PubMed

    Wills, Kiri L; Petrie, Gavin N; Millett, Geneva; Limebeer, Cheryl L; Rock, Erin M; Niphakis, Micah J; Cravatt, Benjamin F; Parker, Linda A

    2016-06-01

    Both CB1 receptor antagonism and agonism, in particular by 2-arachidonyl glycerol (2-AG), have been shown to reduce somatic symptoms of morphine withdrawal (MWD). Here we evaluated the effects of both systemic pretreatment with the monoacylglycerol lipase (MAGL) inhibitor MJN110 (which selectively elevates 2-AG) and central administration of both MJN110 and the CB1 antagonist (AM251) on the affective properties of MWD. Acute MWD induced place aversion occurs when naloxone is administered 24 h following a single exposure to a high dose of morphine. Systemic pretreatment with the MAGL inhibitor, MJN110, prevented the aversive effects of acute MWD by a CB1 receptor-dependent mechanism. Furthermore, in a double dissociation, AM251 infusions into the central amygdala, but MJN110 infusions into the basolateral amygdala, interfered with the naloxone-precipitated MWD induced place aversion. As well, MJN110, but not AM251, infusions into the interoceptive insular cortex (a region known to be activated in acute MWD) also prevented the establishment of the place aversion by a CB1 mechanism of action. These findings reveal the respective sites of action of systemically administered MJN110 and AM251 in regulating the aversive effects of MWD. PMID:26647976

  16. Sex Differences between CRF1 Receptor Deficient Mice following Naloxone-Precipitated Morphine Withdrawal in a Conditioned Place Aversion Paradigm: Implication of HPA Axis

    PubMed Central

    García-Carmona, Juan-Antonio; Baroja-Mazo, Alberto; Milanés, María-Victoria; Laorden, María Luisa

    2015-01-01

    Background Extinction period of positive affective memory of drug taking and negative affective memory of drug withdrawal, as well as the different response of men and women might be important for the clinical treatment of drug addiction. We investigate the role of corticotropin releasing factor receptor type one (CRF1R) and the different response of male and female mice in the expression and extinction of the aversive memory. Methodology/Principal Finding We used genetically engineered male and female mice lacking functional CRF1R. The animals were rendered dependent on morphine by intraperitoneally injection of increasing doses of morphine (10–60 mg/kg). Negative state associated with naloxone (1 mg/kg s.c.)-precipitated morphine withdrawal was examined by using conditioned place aversion (CPA) paradigm. No sex differences for CPA expression were found in wild-type (n = 29) or CRF1R knockout (KO) mice (n = 29). However, CRF1R KO mice presented less aversion score than wild-type mice, suggesting that CRF1R KO mice were less responsive than wild-type to continuous associations between drug administration and environmental stimuli. In addition, CPA extinction was delayed in wild-type and CRF1R KO male mice compared with females of both genotypes. The genetic disruption of the CRF1R pathway decreased the period of extinction in males and females suggesting that CRF/CRF1R is implicated in the duration of aversive memory. Our results also showed that the increase in adrenocorticotropic hormone (ACTH) levels observed in wild-type (n = 11) mice after CPA expression, were attenuated in CRF1R KO mice (n = 10). In addition, ACTH returned to the baseline levels in males and females once CPA extinction was finished. Conclusion/Significance These results suggest that, at least, CPA expression is partially due to an increase in plasma ACTH levels, through activation of CRF1R, which can return when CPA extinction is finished. PMID:25830629

  17. Rats that binge eat fat-rich food do not show somatic signs or anxiety associated with opiate-like withdrawal: implications for nutrient-specific food addiction behaviors.

    PubMed

    Bocarsly, Miriam E; Berner, Laura A; Hoebel, Bartley G; Avena, Nicole M

    2011-10-24

    Previous studies suggest that binge eating sugar leads to behavioral and neurochemical changes similar to those seen with drug addiction, including signs of opiate-like withdrawal. Studies are emerging that show multiple neurochemical and behavioral indices of addiction when animals overeat a fat-rich diet. The goal of the present study was to utilize liquid and solid diets high in sugar and fat content to determine whether opiate-like withdrawal is seen after binge consumption of these diets in Sprague-Dawley rats. Control groups were given ad libitum access to the sweet-fat food or standard chow. All rats were then given a battery of tests to measure signs of opiate-like withdrawal, which included somatic signs of distress, elevated plus-maze anxiety, and locomotor hypoactivity. Neither naloxone-precipitated (3 mg/kg) nor deprivation-induced withdrawal was observed in rats that were maintained on a nutritionally complete pelleted sweet-fat diet or a sweet, high-fat diet supplemented with standard rodent chow. Naloxone-precipitated withdrawal was also not seen in rats fed a liquid sweet-fat food. Further, body weight reduction to 85%, which is known to potentiate the reinforcing effects of substances of abuse, did not affect naloxone-precipitated signs of opiate-like withdrawal. Thus, unlike previous findings reported regarding rats with binge access to a sucrose solution, rats that binge eat sweet-fat combinations do not show signs of opiate-like withdrawal under the conditions tested. These data support the idea that excessive consumption of different nutrients can induce behaviors associated with addiction in different ways, and that the behaviors that could characterize "food addiction" may be subtyped based on the nutritional composition of the food consumed. PMID:21635910

  18. Adenosine receptor agonists attenuate and adenosine receptor antagonists exacerbate opiate withdrawal signs.

    PubMed

    Kaplan, G B; Sears, M T

    1996-01-01

    Previous studies have demonstrated a role for adenosine in mediating opiate effects. Adenosine receptors and their functions have been shown to be regulated by chronic opiate treatment. This study examines the role of adenosine receptors in the expression of opiate withdrawal behaviors. The effects of single doses of parenterally administered adenosine receptor subtype-selective agonists and antagonists on opiate withdrawal signs in morphine-dependent mice were measured. Mice received subcutaneous morphine pellet treatment for 72 h and then underwent naloxone-precipitated withdrawal after pretreatment with adenosinergic agents. Adenosine agonists attenuated different opiate withdrawal signs. The A1 agonist R-N6(phenylisopropyl)adenosine (0, 0.01, 0.02 mg/kg, IP) significantly reduced wet dog shakes and withdrawal diarrhea, while the A2a-selective agonist 2-p-(2-carboxethyl)phenylethylamino-5'-N-ethylcarboxamido adenosine or CGS 21680 (0, 0.01, 0.05 mg/kg, IP) significantly inhibited teeth chattering and forepaw treads. Adenosine receptor antagonists enhanced different opiate withdrawal signs. The adenosine A1 antagonist 1,3-dipropyl-8-cyclopentylxanthine (0, 1, 10 mg/kg, IP) significantly increased weight loss and the A2 antagonist, 3,7-dimethyl-1-propargylxanthine (0, 1 and 10 mg/kg, IP) enhanced wet dog shakes and withdrawal diarrhea. Treatment effects of adenosinergic agents were not due to nonspecific motor effects, as demonstrated by activity monitoring studies. These results support a role for adenosine receptors in the expression of opiate withdrawal and suggest the potential utility of adenosine agonists in its treatment. PMID:8741956

  19. [Extension of the concept of withdrawal signs].

    PubMed

    Kato, Shin

    2015-12-01

    If the conditions including normal-dose dependence in which withdrawal signs are observed in the absence of definite psychic dependence are classified as dependence, this classification should be regarded as inappropriate extension of the concept of drug dependence. These conditions should be diagnosed as 'withdrawal' as specified by the DSM-5 or ICD-10. Advancements of research have clarified that an increased number of drugs cause withdrawal signs. Some Japanese researchers use the concept of 'withdrawal signs of psychic dependence.' Their definition of drug dependence and concept of withdrawal signs, however, are different from the definition established by the WHO and the researchers specializing in this field. Thus, the concept of 'withdrawal signs of psychic dependence' raises a lot of questions. PMID:26964289

  20. A protein kinase inhibitor, H-7, blocks naloxone-precipitated changes in dopamine and its metabolites in the brains of opioid-dependent rats.

    PubMed

    Tokuyama, S; Ho, I K; Yamamoto, T

    2000-07-15

    The influence of an inhibitor of cAMP-dependent protein kinase and protein kinase C, H-7 [1-(5-isoquinolinesulfonyl)-2-methylpiperazine], on naloxone (an opioid receptor antagonist)-precipitated withdrawal signs and changes in levels of dopamine (DA) and its metabolites in morphine- or butorphanol-dependent rats was investigated. Animals were infused continuously with morphine (a mu-opioid receptor agonist) or butorphanol (a mu/delta/kappa mixed opioid receptor agonist) for 3 days. Naloxone precipitated withdrawal syndrome and decreased the levels of DA in the cortex, striatum, and midbrain; 3, 4-dihydroxyphenylacetic acid (DOPAC) in the cortex, striatum, limbic areas, and midbrain; and homovanilic acid (HVA) in the striatum, limbic areas, and midbrain regions. In animals rendered dependent on butorphanol, the results obtained were similar to those of morphine-dependent rats except for the changes in DOPAC levels. Concomitant infusion of H-7 and opioid blocked both the expression of withdrawal signs and the decreases in DA, DOPAC, and HVA levels in a dose-dependent manner. These results suggest that the enhancement of cAMP-dependent protein kinase and/or protein kinase C activity accompanying the increase of DA neuron activity during continuous infusion of opioids leads to an abrupt reduction in levels of DA and its metabolites precipitated by naloxone, which is intimately involved in the expression of physical dependence on opioids. PMID:10922515

  1. Rats that binge eat fat-rich food do not show somatic signs or anxiety associated with opiate-like withdrawal: implications for nutrient-specific food addiction behaviors

    PubMed Central

    Bocarsly, Miriam E.; Berner, Laura A.; Hoebel, Bartley G.; Avena, Nicole M.

    2012-01-01

    Previous studies suggest that binge eating sugar leads to behavioral and neurochemical changes similar to those seen with drug addiction, including signs of opiate-like withdrawal. Studies are emerging that show multiple neurochemical and behavioral indices of addiction when animals overeat a fat-rich diet. The goal of the present study was to utilize liquid and solid diets high in sugar and fat content to determine whether opiate-like withdrawal is seen after binge consumption of these diets in Sprague Dawley rats. Control groups were given ad libitum access to the sweet-fat food or standard chow. All rats were then given a battery of tests to measure signs of opiate-like withdrawal, which included somatic signs of distress, elevated plus-maze anxiety, and locomotor hypoactivity. Neither naloxone-precipitated (3 mg/kg) nor deprivation-induced withdrawal was observed in rats that were maintained on a nutritionally complete pelleted sweet-fat diet, a sweet, high-fat diet supplemented with standard rodent chow, or a liquid sweet-fat food. Further, body weight reduction to 85%, which is known to potentiate the reinforcing effects of substance of abuse, did not affect naloxone-precipitated signs of opiate-like withdrawal. Thus, unlike previous findings reported regarding rats with binge access to a sucrose solution, rats that binge eat sweet-fat combinations do not show signs of opiate-like withdrawal under the conditions tested. These data support the idea that excessive consumption of different nutrients can induce behaviors associated with addiction in different ways, and that the behaviors that could characterize “food addiction” may be subtyped based on the nutritional composition of the food consumed. PMID:21635910

  2. Reduced emotional signs of opiate withdrawal in rats selectively bred for low (LoS) versus high (HiS) saccharin intake

    PubMed Central

    Radke, Anna K.; Holtz, Nathan A.; Gewirtz, Jonathan C.; Carroll, Marilyn E.

    2013-01-01

    Rationale Rats bred for high (HiS) and low (LoS) saccharin intake exhibit divergent behavioral responses to multiple drugs of abuse, with HiS rats displaying greater vulnerability to drug taking. Previous research indicates that this effect may be due to increased sensitivity to reward in HiS rats and to the aversive effects of acute drug administration in LoS rats. Objective The current study investigated whether HiS and LoS rats also exhibit different behavioral signs of withdrawal following one or repeated opiate exposures. Methods Emotional signs of opiate withdrawal were assessed with potentiation of the acoustic startle reflex and conditioned place aversion (CPA) in male and female HiS and LoS rats. Startle was measured before and 4 h after a 10 mg/kg injection of morphine on days 1, 2, and 7 of opiate exposure. CPA was induced with a two-day, naloxone-precipitated conditioning paradigm. Somatic signs of withdrawal and weight loss were used also measured. Results Male and female LoS rats exhibited lower startle potentiation than HiS rats on the seventh day of morphine exposure. LoS male rats also failed to develop a CPA to morphine withdrawal. No differences in physical withdrawal signs were observed between HiS and LoS rats, but males of both lines had more physical signs of withdrawal than females. Conclusions These results suggest that LoS rats are less vulnerable to the negative emotional effects of morphine withdrawal than HiS rats. A less severe withdrawal syndrome may contribute to decreased levels of drug taking in the LoS line. PMID:23254375

  3. Blockade of Endocannabinoid Hydrolytic Enzymes Attenuates Precipitated Opioid Withdrawal Symptoms in MiceS⃞

    PubMed Central

    Ramesh, Divya; Ross, Gracious R.; Schlosburg, Joel E.; Owens, Robert A.; Abdullah, Rehab A.; Kinsey, Steven G.; Long, Jonathan Z.; Nomura, Daniel K.; Sim-Selley, Laura J.; Cravatt, Benjamin F.; Akbarali, Hamid I.

    2011-01-01

    Δ9-Tetrahydrocannbinol (THC), the primary active constituent of Cannabis sativa, has long been known to reduce opioid withdrawal symptoms. Although THC produces most of its pharmacological actions through the activation of CB1 and CB2 cannabinoid receptors, the role these receptors play in reducing the variety of opioid withdrawal symptoms remains unknown. The endogenous cannabinoids, N-arachidonoylethanolamine (anandamide; AEA) and 2-arachidonylglycerol (2-AG), activate both cannabinoid receptors but are rapidly metabolized by fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL), respectively. The objective of this study was to test whether increasing AEA or 2-AG, via inhibition of their respective hydrolytic enzymes, reduces naloxone-precipitated morphine withdrawal symptoms in in vivo and in vitro models of opioid dependence. Morphine-dependent mice challenged with naloxone reliably displayed a profound withdrawal syndrome, consisting of jumping, paw tremors, diarrhea, and weight loss. THC and the MAGL inhibitor 4-nitrophenyl 4-(dibenzo[d][1,3]dioxol-5-yl(hydroxy)methyl)piperidine-1-carboxylate (JZL184) dose dependently reduced the intensity of most measures through the activation of CB1 receptors. JZL184 also attenuated spontaneous withdrawal signs in morphine-dependent mice. The FAAH inhibitor N-(pyridin-3-yl)-4-(3-(5-(trifluoromethyl)pyridin-2-yloxy)benzyl)-piperdine-1-carboxamide (PF-3845) reduced the intensity of naloxone-precipitated jumps and paw flutters through the activation of CB1 receptors but did not ameliorate incidence of diarrhea or weight loss. In the final series of experiments, we investigated whether JZL184 or PF-3845 would attenuate naloxone-precipitated contractions in morphine-dependent ilea. Both enzyme inhibitors attenuated the intensity of naloxone-induced contractions, although this model does not account mechanistically for the autonomic withdrawal responses (i.e., diarrhea) observed in vivo. These results indicate

  4. Effect of environmental enrichment on physical and psychological dependence signs and voluntary morphine consumption in morphine-dependent and morphine-withdrawn rats.

    PubMed

    Hammami-Abrand Abadi, Arezoo; Miladi-Gorji, Hossein; Bigdeli, Imanollah

    2016-04-01

    This study was designed to examine the effect of environmental enrichment during morphine dependency and withdrawal on the severity of naloxone-precipitated withdrawal signs, anxiety, and depressive-like behaviors and voluntary morphine consumption in morphine-dependent rats. The rats were injected with bi-daily doses (10 mg/kg, 12 h intervals) of morphine for 14 days following rearing in a standard environment (SE) or enriched environment (EE) during the development of morphine dependence and withdrawal. Then, rats were tested for withdrawal signs after naloxone injection, anxiety (the elevated plus maze) and depression-related behavior (sucrose preference test), and voluntary consumption of morphine using a two-bottle choice paradigm, in morphine-dependent and morphine-withdrawn rats. The results showed that EE decreased naloxone-precipitated withdrawal signs, but not anxiety or sucrose preference during dependence on morphine. The EE-withdrawn rats showed an increase in the elevated plus maze open arm time and entries and higher levels of sucrose preference than SE rats. Voluntary consumption of morphine was lower in the EE-withdrawn rats than in the SE groups in the second period of drug intake. Thus, exposure to EE reduced the severity of morphine dependence and voluntary consumption of morphine, alongside reductions in anxiety and depression-related behavior in morphine-withdrawn rats. PMID:26397757

  5. The selective mGlu2/3 receptor agonist LY354740 attenuates morphine-withdrawal-induced activation of locus coeruleus neurons and behavioral signs of morphine withdrawal.

    PubMed

    Vandergriff, J; Rasmussen, K

    1999-02-01

    Naltrexone-precipitated morphine withdrawal induces hyperactivity of locus coeruleus (LC) neurons, as well as a plethora of behavioral withdrawal signs. Previous research has demonstrated that an increased release of glutamate and activation of AMPA receptors, particularly in the LC, play an important role in opiate withdrawal. LY354740 is a novel Group II metabotropic glutamate mGlu2/3 receptor agonist that decreases the release of glutamate. Therefore, we investigated the effect of LY354740 on naltrexone-precipitated morphine-withdrawal-induced activation of LC neurons and behavioral signs of morphine withdrawal. In in vivo recordings from anesthetized rats, pretreatment with LY354740 (3-30 mg/kg, s.c.) dose-dependently attenuated the morphine-withdrawal-induced activation of LC neurons. In unanesthetized, morphine-dependent animals, pretreatment with LY354740 (3-30 mg/kg, s.c.) dose-dependently suppressed the severity and occurrence of many naltrexone-precipitated morphine-withdrawal signs. These results indicate mGlu2/3 receptor agonists: (1) can attenuate the morphine-withdrawal-induced activation of LC neurons and many behavioral signs of morphine withdrawal; and (2) may have therapeutic effects in man for the treatment of opiate withdrawal. PMID:10218862

  6. Dipeptides delay the onset of morphine withdrawal in the mouse.

    PubMed

    Kovács, G L; Szontágh, L; Baláspiri, L; Telegdy, G

    1984-01-01

    The effect of dipeptides was studied on naloxone-precipitated morphine withdrawal in the mouse. In accordance with previous data, s.c. treatment with Z-prolyl-D-leucine delayed the onset of withdrawal jumpings . Replacement of L-proline by L-glutamate or L-pyroglutamate resulted in dipeptides which were more potent in morphine withdrawal than was Z-prolyl-D-leucine. PMID:6540034

  7. Effects of Acute and Repeated Administration of Oxycodone and Naloxone-Precipitated Withdrawal on Intracranial Self-Stimulation in Rats.

    PubMed

    Wiebelhaus, Jason M; Walentiny, D Matthew; Beardsley, Patrick M

    2016-01-01

    Incidence of prescription opioid abuse and overdose, often led by oxycodone, continues to increase, producing twice as many overdose deaths as heroin. Surprisingly, preclinical reports relevant to oxycodone's abuse-related effects are relatively sparse considering its history and patient usage. The goal of this study was to characterize dose- and time-dependent effects of acute and repeated oxycodone administration in a frequency-rate intracranial self-stimulation (ICSS) procedure, an assay often predictive of drug-related reinforcing effects, in male Sprague-Dawley rats. We hypothesized that oxycodone would produce a biphasic profile of rate-increasing and rate-decreasing effects maintained by ICSS similar to μ-opioid receptor agonists. Oxycodone (0.03, 0.3, 1, and 3 mg/kg, s.c.) produced dose- and time-dependent alterations on ICSS, with the predicted biphasic profile of rate-increasing effects at lower stimulation frequencies followed by rate-decreasing effects at higher frequencies. Peak effects were observed between 30 and 60 minutes, which were reversed by naloxone pretreatment (30 minutes). Tolerance to rate-decreasing effects was observed over a 5-day period when rats were treated with 1 mg/kg oxycodone twice a day. Subsequently, the dosing regimen was increased to 3 mg/kg twice a day over 10 days, although further marked tolerance did not develop. When then challenged with 10 mg/kg naloxone, a significant suppression below baseline levels of ICSS-maintained responding occurred indicative of dependence that recovered to baseline within 5 hours. The results of this study provide the first report of acute and chronic effects of oxycodone on responding maintained by ICSS presentation and the use of ICSS-maintained responding to characterize its tolerance and dependence effects. PMID:26491062

  8. Rimonabant-induced Delta9-tetrahydrocannabinol withdrawal in rhesus monkeys: discriminative stimulus effects and other withdrawal signs.

    PubMed

    Stewart, Jennifer L; McMahon, Lance R

    2010-07-01

    Marijuana-dependent individuals report using marijuana to alleviate withdrawal, suggesting that pharmacotherapy of marijuana withdrawal could promote abstinence. To identify potential pharmacotherapies for marijuana withdrawal, this study first characterized rimonabant-induced Delta(9)-tetrahydrocannabinol (Delta(9)-THC) withdrawal in rhesus monkeys by using drug discrimination and directly observable signs. Second, drugs were examined for their capacity to modify cannabinoid withdrawal. Monkeys receiving chronic Delta(9)-THC (1 mg/kg/12 h s.c.) discriminated the cannabinoid antagonist rimonabant (1 mg/kg i.v.) under a fixed ratio schedule of stimulus-shock termination. The discriminative stimulus effects of rimonabant were dose-dependent (ED(50) = 0.25 mg/kg) and accompanied by head shaking. In the absence of chronic Delta(9)-THC treatment (i.e., in nondependent monkeys), a larger dose (3.2 mg/kg) of rimonabant produced head shaking and tachycardia. Temporary discontinuation of Delta(9)-THC treatment resulted in increased responding on the rimonabant lever, head shaking, and activity during the dark cycle. The rimonabant discriminative stimulus was attenuated fully by Delta(9)-THC (at doses larger than mg/kg/12 h) and the cannabinoid agonist CP 55940 [5-(1,1-dimethylheptyl)-2-[5-hydroxy-2-(3-hydroxypropyl)cyclohexyl]phenol], and partially by the cannabinoid agonist WIN 55212-2 [(R)-(+)-[2, 3-dihydro-5-methyl-3-(4-morpholinylmethyl)pyrrolo[1,2,3-de]-1,4-benzoxazin-6-yl]-1-naphthalenylmethanone mesylate] and the alpha(2)-adrenergic agonist clonidine. In contrast, a benzodiazepine (diazepam) and monoamine agonist (cocaine) did not attenuate the rimonabant discriminative stimulus. Head shaking was attenuated by all test compounds. These results show that the discriminative stimulus effects of rimonabant in Delta(9)-THC-treated monkeys are a more pharmacologically selective measure of cannabinoid withdrawal than rimonabant-induced head shaking. These results suggest

  9. Thymus Daenensis Extract and Essential Oils Effects on Morphine Withdrawal Signs in Mice

    PubMed Central

    Khodayar, Mohammad Javad; Taherzadeh, Esmaeil; Siahpoosh, Amir; Mansourzadeh, Zahra; Tabatabaei, Seyed Amir Hossein

    2014-01-01

    Background: Thymus species are well known medicinal plants which the previous studies suggested the involvement of the opioid system in them. Objectives: This study aimed to investigate the effects of methanolic extract and essential oil of aerial parts of Thymus daenensis (TD), an endemic aromatic medicinal plant of Iran, on morphine withdrawal syndrome in mice. Materials and Methods: Experiments were performed in two groups of five, each group treated with extracts or essential oils of TD. Dependency was induced by subcutaneous injection of morphine for three consecutive days. On the fourth day, the last dose of morphine was injected two hours prior to intraperitoneal injection of naloxone while the extract or essential oil of TD was administered 30 minutes before naloxone. A period of 20 minutes after naloxone injection was considered the critical period of the withdrawal syndrome. The number of jumps, standing, leaning, and the weight of stools were recorded as withdrawal signs. Results: The 200 mg/kg and 400 mg/kg doses of extract and all doses of essential oil decreased significantly the number of jumps, standing, leaning and the weight of stool. Administration of 100 mg/kg of extract only decreased the weight of stool and had no effect on the other factors. Conclusions: Extract and essential oil of TD attenuates morphine withdrawal behaviors in mice and may be useful in alleviating the signs and symptoms of opiate withdrawal syndrome in human. PMID:25237649

  10. Disruption of the CRF2 Receptor Pathway Decreases the Somatic Expression of Opiate Withdrawal

    PubMed Central

    Papaleo, Francesco; Ghozland, Sandy; Ingallinesi, Manuela; Roberts, Amanda J; Koob, George F; Contarino, Angelo

    2009-01-01

    Escape from the extremely aversive opiate withdrawal symptoms powerfully motivates compulsive drug-seeking and drug-taking behaviors. The corticotropin-releasing factor (CRF) system is hypothesized to mediate the motivational properties of drug dependence. CRF signaling is transmitted by two receptor pathways, termed CRF1 and CRF2. To investigate the role for the CRF2 receptor pathway in somatic opiate withdrawal, in the present study we used genetically engineered mice deficient in the CRF2 receptor (CRF2−/−). We employed a novel, clinically relevant mouse model of ‘spontaneous’ opiate withdrawal as well as a classical opioid receptor antagonist (naloxone)-precipitated opiate withdrawal paradigm. To induce opiate dependence, mice were treated with intermittent escalating morphine doses (20–100 mg/kg, i.p.). We found that 8–128 h after the last opiate injection, CRF2−/− mice showed decreased levels of major somatic signs of spontaneous opiate withdrawal, such as paw tremor and wet dog shake, as compared to wild-type mice. Similarly, challenge with naloxone 2 h after the last morphine injection induced lower levels of paw tremor and wet dog shake in CRF2−/− mice as compared to wild-type mice. Despite the differences in somatic signs, wild-type and CRF2−/− mice displayed similar plasma corticosterone responses to opiate dosing and withdrawal, indicating a marginal role for the hypothalamus–pituitary–adrenal axis in the CRF2 receptor mediation of opiate withdrawal. Our results unravel a novel role for the CRF2 receptor pathway in opiate withdrawal. The CRF2 receptor pathway might be a critical target of therapies aimed at alleviating opiate withdrawal symptoms and reducing relapse to drug intake. PMID:18288089

  11. GC-MS-based plasma metabolomic investigations of morphine dependent rats at different states of euphoria, tolerance and naloxone-precipitated withdrawal.

    PubMed

    Liu, Ruoxu; Cheng, Jianhua; Yang, Jingwen; Ding, Xinghua; Yang, Shuguang; Dong, Fangting; Guo, Ning; Liu, Shaojun

    2015-06-01

    Long-term or excessive application of morphine leads to tolerance and addiction, which hindered its conventional applications as a drug. Although tremendous progress has been made on the mechanisms of morphine, crucial evidence elaborating the neurobiological basis of tolerance and dependence is still lacking. To further explore the physiological adaptions during morphine's application, a systematic screening of small molecules in blood has been carried out. The plasma of morphine dependent rats was collected at different time points with or without naloxone treatment, and was analyzed by gas chromatography-mass spectrometry (GC-MS). Partial least squares discriminate analysis (PLS-DA) and the Student's t Tests with the false discovery rate (FDR) correction were conducted on the normalized data for the distinction of groups and the identification of the most contributed metabolites. Clear separation is observed between different treatments, and 29 out of 41 metabolites changes significantly compared with the corresponding controls. The concentration of threonine, glycine, serine, beta-d-glucose and oxalic acid are consistently changed in all morphine treated groups compared with controls. Through this experiment we find characteristic metabolites in different dependent states and discuss the possible compensation effects. The interpretation of these metabolites would throw light on the biological effects of morphine and reveal the possibilities to become marker of morphine addiction. PMID:25472920

  12. Effects of high-dose selegiline on morphine reinforcement and precipitated withdrawal in dependent rats.

    PubMed

    Grasing, K; He, S

    2005-02-01

    Selegiline is an irreversible inhibitor of monoamine oxidase (MAO) with psychostimulant and neuroprotective effects. Several lines of evidence suggest that treatment with selegiline at doses that exceed levels required for inhibition of MAO can produce distinct pharmacologic effects. The purpose of this study was to evaluate the effects of chronic treatment with high-dose selegiline on extinction responding, cue-induced reinstatement, morphine reinforcement and naloxone-precipitated withdrawal. After pretreatment with noncontingent morphine to establish opiate dependence, rats acquired self-administration of 3.2 mg/kg per injection of morphine under a progressive ratio schedule. Daily treatment with saline or 6.4 mg/kg per day of selegiline was then administered over extinction, reinstatement and re-acquisition of morphine self-administration. To enhance or diminish the potential for psychostimulant effects, selegiline was administered either immediately prior to (pre-session) or 1 h following (post-session) extinction, reinstatement and self-administration sessions. Pre-session selegiline decreased the number of ratios completed on days 2, 3 and 4 of extinction, and decreased morphine self-administration during all four re-acquisition sessions. When administered at the same dose level, post-session selegiline decreased responding on the fourth extinction session, and was ineffective in modifying re-acquisition of self-administration. Selegiline administered by either schedule did not modify cue-induced reinstatement. Daily treatment with 6.4 mg/kg per day of selegiline did not modify self-administration of food under a progressive ratio schedule. Acute treatment with single, 6.4 mg/kg doses of selegiline attenuated naloxone-induced increases in ptosis and global withdrawal score, but did not modify any other sign of withdrawal or global withdrawal score calculated without ratings of ptosis. In conclusion, high-dose selegiline can attenuate extinction responding

  13. Plasma malondialdehyde levels and opiate withdrawal signs observed in rats treated with morphine plus naloxone: effects of alpha-lipoic acid administration.

    PubMed

    Pinelli, Arnaldo; Cighetti, Giuliana; Trivulzio, Silvio

    2008-08-01

    A number of experimental studies have found that reactive oxygen species are involved during morphine treatment or withdrawal. The aims of this study were to analyse whether morphine administration and/or removal are related to peroxide generation and/or signs of withdrawal in rats, and whether the changes in antioxidant status induced by the administration of an antioxidant may modify peroxide levels and behavioural signs. We injected morphine or morphine and naloxone into rats and evaluated the plasma levels of peroxide malondialdehyde (MDA) and the appearance of withdrawal signs. We also investigated the effects on these parameters induced by the administration of the antioxidant alpha-lipoic acid (LA). Morphine treatment increased MDA levels. Abrupt naloxone-induced morphine withdrawal caused a further and significant increase in MDA, and the appearance of withdrawal signs such as abnormal fecal excretion, shortened latency times and jumping. The administration of LA lowered MDA levels in the rats treated with morphine or morphine plus naloxone, and also decreased MDA values and abstinence signs in the animals treated with morphine plus naloxone. The effects of LA were attributed to its capacity to scavenge peroxides and interfere with the biogenesis of the arachidonic acid metabolites involved in the expression of abstinence symptoms. PMID:18705754

  14. Opiate withdrawal behavior after focal brain stimulation.

    PubMed

    Williams, D A; Thorn, B E

    1984-11-01

    Electrical stimulation of the brainstem abolishes pain, while continued stimulation induces tolerance to the analgesic effect. Analgesic drugs producing tolerance also induce physical dependence, suggesting that the phenomenon of tolerance is associated with addiction. There is evidence that the neural mechanism for stimulation-produced analgesia is related to the release of opiate substances within the brain. We therefore propose that repeated or protracted brain stimulation elicits dependence upon the endorphins released by electrical stimulation of the neurons themselves. To investigate this possibility, rats were given repetitive bursts of analgesic electrical brain stimulation for two hours. Immediately thereafter, they were injected with the opiate antagonist, naloxone. Behaviors associated with low grade opiate withdrawal were observed. These data suggest that prolonged analgesic stimulation can result in naloxone-precipitated behaviors similar to the behaviors exhibited during opiate withdrawal. PMID:6542676

  15. Exploratory behavior and withdrawal signs in crayfish: chronic central morphine injections and termination effects.

    PubMed

    Imeh-Nathaniel, Adebobola; Okon, Marvin; Huber, Robert; Nathaniel, Thomas I

    2014-05-01

    Functional and evolutionary conservation of neural circuits of reward seeking >is a symbol of survival. It is found in most animals from insects to humans. Exploration is a component of a wide range of drug-elicited behaviors that reflects an appetitive motivational state when animals seek natural rewards such as food, water, and shelter for survival. Not only does the characterization of exploratory behaviors indicate the specific components of appetitive motor patterns, it also reveals how exploratory behavioral patterns are implemented via increased incentive salience of environmental stimuli. The current work demonstrates that novel stimuli appear to directly augment exploration in crayfish, while injections of morphine directly into the brain of crayfish enhanced robust arousal resulting in increased locomotion and exploration of the environment. Elimination of morphine suppressed exploratory motor patterns. Crayfish displayed atypical behavioral changes evident of withdrawal-like states when saline is injected into the brain. With proven evidence of rewarding to the exposure to mammalian drugs of abuse, modularly organized and experimentally accessible nervous system makes crayfish exceptionally suitable for characterizing the central workings of addiction at its key behavioral and neuroanatomic locations. PMID:24512767

  16. Assessment of affective and somatic signs of ethanol withdrawal in C57BL/6J mice using a short term ethanol treatment

    PubMed Central

    Perez, EE; De Biasi, M

    2015-01-01

    Alcohol is one of the most prevalent addictive substances in the world. Withdrawal symptoms result from abrupt cessation of alcohol consumption in habitual drinkers. The emergence of both affective and physical symptoms produces a state that promotes relapse. Mice provide a preclinical model that could be used to study alcohol dependence and withdrawal while controlling for both genetic and environmental variables. The use of a liquid ethanol diet offers a reliable method for the induction of alcohol dependence in mice, but this approach is impractical when conducting high throughput pharmacological screens or when comparing multiple strains of genetically engineered mice. The goal of this study was to compare withdrawal associated behaviors in mice chronically treated with a liquid ethanol diet vs. mice treated with a short-term ethanol treatment that consisted of daily ethanol injections containing the alcohol dehydrogenase inhibitor, 4-methylpyrazole. Twenty-four hours after ethanol treatment, mice were tested in the open field arena, the elevated plus maze, the marble burying test or for changes in somatic signs during spontaneous ethanol withdrawal. Anxiety-like and compulsive-like behavior, as well as physical signs, were all significantly elevated in mice undergoing withdrawal, regardless of the route of ethanol administration. Therefore, a short-term ethanol treatment can be utilized as a screening tool for testing genetic and pharmacological agents before investing in a more time consuming ethanol treatment. PMID:25817777

  17. The α3β4* nicotinic acetylcholine receptor subtype mediates nicotine reward and physical nicotine withdrawal signs independently of the α5 subunit in the mouse

    PubMed Central

    Jackson, Kia J.; Sanjakdar, Sarah S.; Muldoon, Pretal P.; McIntosh, J. Michael; Damaj, M. Imad

    2013-01-01

    The 15q25 gene cluster contains genes that code for the α5, α3, and β4 nicotinic acetylcholine receptor (nAChRs) subunits, and in human genetic studies, has shown the most robust association with smoking behavior and nicotine dependence to date. The limited available animal studies implicate a role for the α5 and β4 nAChR subunits in nicotine dependence and withdrawal; however studies focusing on the behavioral role of the α3β4* nAChR receptor subtype in nicotine dependence are lacking. Because of the apparent role of the α3β4* nAChR subtype in nicotine dependence, the goal of the current study was to better evaluate the involvement of this subtype in nicotine mediated behavioral responses. Using the selective α3β4* nAChR antagonist, α-conotoxin AuIB, we assessed the role of α3β4* nAChRs in acute nicotine, nicotine reward, and physical and affective nicotine withdrawal. Because α5 has also been implicated in nicotine dependence behaviors in mice and can form functional receptors with α3β4*, we also evaluated the role of the α3β4α5* nAChR subtype in nicotine reward and somatic nicotine withdrawal signs by blocking the α3β4* nAChR subtype in α5 nAChR knockout mice with AuIB. AuIB had no significant effect on acute nicotine behaviors, but dose-dependently attenuated nicotine reward and physical withdrawal signs, with no significant effect in affective withdrawal measures. Interestingly, AuIB also attenuated nicotine reward and somatic signs in α5 nAChR knockout mice. This study shows that α3β4* nAChRs mediate nicotine reward and physical nicotine withdrawal, but not acute nicotine behaviors or affective nicotine withdrawal signs in mice. The α5 subunit is not required in the receptor assembly to mediate these effects. Our findings suggest an important role for the α3β4* nAChR subtype in nicotine reward and physical aspects of the nicotine withdrawal syndrome. PMID:23416040

  18. Alcohol withdrawal

    MedlinePlus

    ... Seeing or feeling things that aren't there (hallucinations) Seizures Severe confusion ... alcohol withdrawal. You will be watched closely for hallucinations and other signs of delirium tremens. Treatment may ...

  19. Alcohol withdrawal.

    PubMed

    Manasco, Anton; Chang, Shannon; Larriviere, Joseph; Hamm, L Lee; Glass, Marcia

    2012-11-01

    Alcohol withdrawal is a common clinical condition that has a variety of complications and morbidities. The manifestations can range from mild agitation to withdrawal seizures and delirium tremens. The treatments for alcohol withdrawal include benzodiazepines, anticonvulsants, beta-blockers and antihypertensives. Although benzodiazepines are presently a first-line therapy, there is controversy regarding the efficacies of these medications compared with others. Treatment protocols often involve one of two contrasting approaches: symptom-triggered versus fixed-schedule dosing of benzodiazepines. We describe these protocols in our review and examine the data supporting symptom-triggered dosing as the preferred method for most patients in withdrawal.The Clinical Institute Withdrawal Assessment for Alcohol scoring system for alcohol withdrawal streamlines care, optimizes patient management, and is the best scale available for withdrawal assessment. Quality improvement implications for inpatient management of alcohol withdrawal include increasing training for signs of withdrawal and symptom recognition, adding new hospital protocols to employee curricula, and ensuring manageable patient-to-physician and patient-to-nurse ratios. PMID:23128805

  20. Oral noribogaine shows high brain uptake and anti-withdrawal effects not associated with place preference in rodents.

    PubMed

    Mash, Deborah C; Ameer, Barbara; Prou, Delphine; Howes, John F; Maillet, Emeline L

    2016-07-01

    This study investigated the effects of noribogaine, the principal metabolite of the drug ibogaine, on substance-related disorders. In the first experiment, mice chronically treated with morphine were subjected to naloxone-precipitated withdrawal two hours after oral administration of noribogaine. Oral noribogaine dose dependently decreased the global opiate withdrawal score by up to 88% of vehicle control with an ED50 of 13 mg/kg. In the second experiment, blood and brain levels of noribogaine showed a high brain penetration and a brain/blood ratio of 7±1 across all doses tested. In a third experiment, rats given oral noribogaine up to 100 mg/kg were tested for abuse liability using a standard biased conditioned place paradigm. Noribogaine-treated rats did not display place preference, suggesting that noribogaine is not perceived as a hedonic stimulus in rodents. Retrospective review of published studies assessing the efficacy of ibogaine on morphine withdrawal shows that the most likely cause of the discrepancies in the literature is the different routes of administration and time of testing following ibogaine administration. These results suggest that the metabolite noribogaine rather than the parent compound mediates the effects of ibogaine on blocking naloxone-precipitated withdrawal. Noribogaine may hold promise as a non-addicting alternative to standard opiate replacement therapies to transition patients to opiate abstinence. PMID:27044509

  1. Attenuation of Withdrawal Signs, Blood Cortisol, and Glucose Level with Various Dosage Regimens of Morphine after Precipitated Withdrawal Syndrome in Mice.

    PubMed

    Motaghinejad, Majid; Sadeghi-Hashjin, Goudarz; Koohi, Mohammad Kazem; Karimian, Seyed Morteza

    2016-01-01

    Morphine withdrawal usually results in unsuccessful outcomes. Despite partial benefits from alternative substances such as methadone, its use may not lead to the desired result due to the lack of mental tranquility during the withdrawal period. In this study, by means of an animal model, morphine itself was used to manage morphine dependence. Forty mice were divided into 5 groups, in which 4 groups became dependent by increasing daily doses of morphine for 7 days (15-45 mg/kg). Afterwards, the animals received morphine for 14 days by either of the following regimens: Once daily 45 mg/kg (positive controls)Increasing the interval (each time 6 hours longer than the previous interval)Irregular interval in every 36, 12 and 24 hours until the 21(th) day12, 24, 36 hours decreasing doses (each time 2.5 mg/kg less than the former dosage). Negative controls received saline solution only. On day 22, total withdrawal index (TWI) was determined by injecting 3 mg/kg of naloxone. Thereafter, blood samples were taken for the measurement of cortisol and glucose levels. TWI significantly decreased in all test groups in comparison with the positive control animals (P<0.001). Cortisol levels significantly decreased when either the dosage or the administration frequencies were decreased on a regular and gradual basis (P<0.005). Blood glucose levels significantly decreased in animals that received decreasing doses of morphine (P<0.005). This study suggests that no other measures may be required in clinical practice except for changing the dosage regimen of morphine for the cessation of self-administration. PMID:26722146

  2. Effects of voluntary and treadmill exercise on spontaneous withdrawal signs, cognitive deficits and alterations in apoptosis-associated proteins in morphine-dependent rats.

    PubMed

    Mokhtari-Zaer, Amin; Ghodrati-Jaldbakhan, Shahrbanoo; Vafaei, Abbas Ali; Miladi-Gorji, Hossein; Akhavan, Maziar M; Bandegi, Ahmad Reza; Rashidy-Pour, Ali

    2014-09-01

    Chronic exposure to morphine results in cognitive deficits and alterations of apoptotic proteins in favor of cell death in the hippocampus, a brain region critically involved in learning and memory. Physical activity has been shown to have beneficial effects on brain health. In the current work, we examined the effects of voluntary and treadmill exercise on spontaneous withdrawal signs, the associated cognitive defects, and changes of apoptotic proteins in morphine-dependent rats. Morphine dependence was induced through bi-daily administrations of morphine (10mg/kg) for 10 days. Then, the rats were trained under two different exercise protocols: mild treadmill exercise or voluntary wheel exercise for 10 days. After exercise training, their spatial learning and memory and aversive memory were examined by a water maze and by an inhibitory avoidance task, respectively. The expression of the pro-apoptotic protein Bax and the anti-apoptotic protein Bcl-2 in the hippocampus were determined by immunoblotting. We found that chronic exposure to morphine impaired spatial and aversive memory and remarkably suppressed the expression of Bcl-2, but Bax expression remained constant. Both voluntary and treadmill exercise alleviated memory impairment, increased the expression of Bcl-2 protein, and only the later suppressed the expression of Bax protein in morphine-dependent animals. Moreover, both exercise protocols diminished the occurrence of spontaneous morphine withdrawal signs. Our findings showed that exercise reduces the spontaneous morphine-withdrawal signs, blocks the associated impairment of cognitive performance, and overcomes morphine-induced alterations in apoptotic proteins in favor of cell death. Thus, exercise may be a useful therapeutic strategy for cognitive and behavioral deficits in addict individuals. PMID:24906198

  3. Noni (Morinda citrifolia L.) fruit extract attenuates the rewarding effect of heroin in conditioned place preference but not withdrawal in rodents.

    PubMed

    Narasingam, Megala; Pandy, Vijayapandi; Mohamed, Zahurin

    2016-05-20

    The present study was designed to investigate the effect of a methanolic extract of Morinda citrifolia Linn. fruit (MMC) on the rewarding effect of heroin in the rat conditioned place preference (CPP) paradigm and naloxone-precipitated withdrawal in mice. In the first experiment, following a baseline preference test (preconditioning score), the rats were subjected to conditioning trials with five counterbalanced escalating doses of heroin versus saline followed by a preference test conducted under drug-free conditions (post-conditioning score) using the CPP test. Meanwhile, in the second experiment, withdrawal jumping was precipitated by naloxone administration after heroin dependence was induced by escalating doses for 6 days (3×/ day). The CPP test results revealed that acute administration of MMC (1, 3, and 5 g/kg body weight (bw), p.o.), 1 h prior to the CPP test on the 12th day significantly reversed the heroin-seeking behavior in a dose-dependent manner, which was similar to the results observed with a reference drug, methadone (3 mg/kg bw, p.o.). On the other hand, MMC (0.5, 1, and 3 g/kg bw, p.o.) did not attenuate the heroin withdrawal jumps precipitated by naloxone. These findings suggest that the mechanism by which MMC inhibits the rewarding effect of heroin is distinct from naloxone-precipitated heroin withdrawal. PMID:26744024

  4. Noni (Morinda citrifolia L.) fruit extract attenuates the rewarding effect of heroin in conditioned place preference but not withdrawal in rodents

    PubMed Central

    Narasingam, Megala; Pandy, Vijayapandi; Mohamed, Zahurin

    2016-01-01

    The present study was designed to investigate the effect of a methanolic extract of Morinda citrifolia Linn. fruit (MMC) on the rewarding effect of heroin in the rat conditioned place preference (CPP) paradigm and naloxone-precipitated withdrawal in mice. In the first experiment, following a baseline preference test (preconditioning score), the rats were subjected to conditioning trials with five counterbalanced escalating doses of heroin versus saline followed by a preference test conducted under drug-free conditions (post-conditioning score) using the CPP test. Meanwhile, in the second experiment, withdrawal jumping was precipitated by naloxone administration after heroin dependence was induced by escalating doses for 6 days (3×/ day). The CPP test results revealed that acute administration of MMC (1, 3, and 5 g/kg body weight (bw), p.o.), 1 h prior to the CPP test on the 12th day significantly reversed the heroin-seeking behavior in a dose-dependent manner, which was similar to the results observed with a reference drug, methadone (3 mg/kg bw, p.o.). On the other hand, MMC (0.5, 1, and 3 g/kg bw, p.o.) did not attenuate the heroin withdrawal jumps precipitated by naloxone. These findings suggest that the mechanism by which MMC inhibits the rewarding effect of heroin is distinct from naloxone-precipitated heroin withdrawal. PMID:26744024

  5. Evidence of an immune system to brain communication axis that affects central opioid functions: muramyl peptides attenuate opiate withdrawal.

    PubMed

    Dougherty, P M; Drath, D B; Dafny, N

    1987-09-11

    Muramyl peptides are metabolic breakdown products of bacterial cell walls formed in vivo by the reticuloendothelial system. These agents have a variety of immune modulatory and neuropharmacologic effects. It has previously been demonstrated that a variety of immune modifying agents can induce alterations in certain behaviors elicited by opiates. In the present study we investigate possible reciprocal interactions between muramyl dipeptides (MDPs) and central opioid systems using three different experimental models: (1) naloxone-precipitated withdrawal behavior in morphine-dependent rats; (2) the tail immersion assay for determination of morphine-induced antinociception and (3) rectal temperature measurement of the pyrogenic activity of MDP. It is shown that two derivatives of MDP attenuate the severity of naloxone-precipitated withdrawal and morphine-induced antinociception. In addition, it is demonstrated that the pyrogenic activity of a stearoyl derivative of MDP is altered by chronic morphine treatment. These findings suggest both novel neuropharmacologic properties of muramyl dipeptides, as well as demonstrate that yet another immune modifier interacts with centrally mediated opioid phenomena. PMID:2824218

  6. Glutamate receptors in the dorsal hippocampus mediate the acquisition, but not the expression, of conditioned place aversion induced by acute morphine withdrawal in rats

    PubMed Central

    Hou, Yuan-yuan; Liu, Yao; Kang, Shuo; Yu, Chuan; Chi, Zhi-qiang; Liu, Jing-gen

    2009-01-01

    Aim: To evaluate the role of glutamate receptors in the dorsal hippocampus (DH) in the motivational component of morphine withdrawal. Methods: NMDA receptor antagonist D-AP5 (5 μg/0.5 μL per side) or AMPA receptor antagonist NBQX (2 μg/0.5 μL per side) was microinjected into DH of rats. Conditioned place aversion (CPA) induced by naloxone-precipitated morphine withdrawal were assessed. Results: Preconditioning microinjection of D-AP5 or NBQX into the DH impaired the acquisition of CPA in acute morphine-dependent rats. However, intra-DH microinjection of D-AP5 or NBQX after conditioning but before the testing session had no effect on the expression of CPA. Conclusion: Our results suggest that NMDA and AMPA receptors in the dorsal hippocampus are involved in the acquisition, but not in the expression, of the negative motivational components of acute morphine withdrawal in rats. PMID:19767765

  7. Drugs affecting brain dopamine interfere with the effect of Z-prolyl-D-leucine on morphine withdrawal.

    PubMed

    Kovács, G L; Telegdy, G; Hódi, K

    1984-09-01

    The dipeptide Z-prolyl-D-leucine (Z-Pro-D-Leu) has been demonstrated to inhibit the development of tolerance to and dependence on morphine in the mouse. Since the dipeptide affects dopamine (DA) utilization in the terminal regions of the mesolimbic and nigrostriatal DA-ergic projections, the question has been studied of whether DA-ergic mechanisms are involved in the action of Z-Pro-D-Leu on morphine withdrawal. Both inhibition of tyrosine hydroxylase by alpha-methyl-p-tyrosine (alpha-MPT) and inhibition of DA receptors by pimozide interfere with the effect of Z-Pro-D-Leu on naloxone-precipitated morphine withdrawal. Inhibition of serotonin (5-HT) synthesis by DL-p-chlorophenylalanine (PCPA), on the other hand, does not modify the effect of the dipeptide. The results argue for a role of DA-ergic mechanisms in the effect of Z-Pro-D-Leu on the development of morphine dependence. PMID:6541792

  8. Intracranial self-stimulation reward thresholds during morphine withdrawal in rats bred for high (HiS) and low (LoS) saccharin intake

    PubMed Central

    Holtz, Nathan A.; Radke, Anna K.; Zlebnik, Natalie E.; Harris, Andrew C.; Carroll, Marilyn E.

    2015-01-01

    Rational Sweet preference is a marker of vulnerability to substance use disorders, and rats selectively bred for high (HiS) vs. low saccharin (LoS) intake display potentiated drug-seeking behaviors. Recent work indicated that LoS rats were more responsive to the negative effects of drugs in several assays. Objective The current study used the intracranial self-stimulation (ICSS) procedure to investigate the anhedonic component of morphine withdrawal in male HiS and LoS rats. Methods Rats were administered morphine (10 mg/kg) or saline for 8 days. To evaluate withdrawal effects, reward thresholds were measured 24 and 28 h following the 8th morphine injection (spontaneous withdrawal) and again for 4 days following daily acute morphine and naloxone (1 mg/kg) administration (precipitated withdrawal). Results Twenty-four hr following the final morphine injection, reward thresholds in LoS rats were significantly elevated compared to reward thresholds in LoS controls, indicating spontaneous withdrawal. This effect was not observed in HiS rats. LoS rats also showed greater elevations of reward thresholds on several days during naloxone-precipitated withdrawal compared to their HiS counterparts. Conclusions LoS rats were more sensitive to morphine withdrawal-mediated elevations in ICSS thresholds than HiS rats. While these differences were generally modest, our data suggest that severity of the negative affective component of opiate withdrawal may be influenced by genotypes related to addiction vulnerability. PMID:25582876

  9. The effect of chronic morphine or methadone exposure and withdrawal on clock gene expression in the rat suprachiasmatic nucleus and AA-NAT activity in the pineal gland.

    PubMed

    Pačesová, D; Novotný, J; Bendová, Z

    2016-07-18

    The circadian rhythms of many behavioral and physiological functions are regulated by the major circadian pacemaker in the suprachiasmatic nucleus. Long-term opiate addiction and drug withdrawal may affect circadian rhythmicity of various hormones or the sleep/activity pattern of many experimental subjects; however, limited research has been done on the long-term effects of sustained opiate administration on the intrinsic rhythmicity in the suprachiasmatic nucleus and pineal gland. Here we compared the effects of repeated daily treatment of rats with morphine or methadone and subsequent naloxone-precipitated withdrawal on the expression of the Per1, Per2, and Avp mRNAs in the suprachiasmatic nucleus and on arylalkylamine N-acetyltransferase activity in the pineal gland. We revealed that 10-day administration and withdrawal of both these drugs failed to affect clock genes and Avp expression in the SCN. Our results indicate that opioid-induced changes in behavioral and physiological rhythms originate in brain structures downstream of the suprachiasmatic nucleus regulatory output pathway. Furthermore, we observed that acute withdrawal from methadone markedly extended the period of high night AA-NAT activity in the pineal gland. This suggests that withdrawal from methadone, a widely used drug for the treatment of opioid dependence, may have stronger impact on melatonin synthesis than withdrawal from morphine. PMID:27070740

  10. Elevated mu-opioid receptor expression in the nucleus of the solitary tract accompanies attenuated withdrawal signs after chronic low dose naltrexone in opiate-dependent rats.

    PubMed

    Van Bockstaele, E J; Rudoy, C; Mannelli, P; Oropeza, V; Qian, Y

    2006-02-15

    We previously described a decrease in withdrawal behaviors in opiate-dependent rats that were chronically treated with very low doses of naltrexone in their drinking water. Attenuated expression of withdrawal behaviors correlated with decreased c-Fos expression and intracellular signal transduction elements [protein kinase A regulatory subunit II (PKA) and phosphorylated cAMP response element binding protein (pCREB)] in brainstem noradrenergic nuclei. In this study, to determine whether similar cellular changes occurred in forebrain nuclei associated with drug reward, expressions of PKA and pCREB were analyzed in the ventral tegmental area, frontal cortex, striatum, and amygdala of opiate-treated rats that received low doses of naltrexone in their drinking water. No significant difference in PKA or pCREB was detected in these regions following drug treatment. To examine further the cellular mechanisms in noradrenergic nuclei that could underlie attenuated withdrawal behaviors following low dose naltrexone administration, the nucleus of the solitary tract (NTS) and locus coeruleus (LC) were examined for opioid receptor (OR) protein expression. Results showed a significant increase in muOR expression in the NTS of morphine-dependent rats that received low doses of naltrexone in their drinking water, and increases in muOR expression were also found to be dose dependent. Protein expression of muOR in the LC and deltaOR in either brain region remained unchanged. In conclusion, our previously reported decreases in c-Fos and PKA expression in the NTS following pretreatment with low doses of naltrexone may be partially explained by a greater inhibition of NTS neurons resulting from increased muOR expression in this region. PMID:16385558

  11. Cocaine withdrawal

    MedlinePlus

    ... this page: //medlineplus.gov/ency/article/000947.htm Cocaine withdrawal To use the sharing features on this page, please enable JavaScript. Cocaine withdrawal occurs when someone who has used a ...

  12. Evidence for the involvement of excitatory amino acid pathways in the development of precipitated withdrawal from acute and chronic morphine: an in vivo voltammetric study in the rat locus coeruleus.

    PubMed

    Hong, M; Milne, B; Jhamandas, K

    1993-09-24

    Previous studies have demonstrated that activation of excitatory amino acid (EAA) pathways projecting to the locus coeruleus may be involved in the increased firing of locus coeruleus (LC) neurons during opioid withdrawal. Using differential normal pulse voltammetry to monitor catechol oxidation current (CA.OC), an index of neuronal activity in the LC, the role of EAA pathways in naloxone precipitated withdrawal after acute and chronic morphine treatment was examined. Acute morphine treatment (10 micrograms i.c.v.) significantly reduced the CA.OC signal in the LC to 54.3 +/- 3.1% of baseline. Naloxone challenge (1 mg/kg i.v.) completely reversed the morphine effect and produced a significant increase in the CA.OC signal above baseline, peak 145.4 +/- 10.1% of baseline. This naloxone-induced rebound response was attenuated by pretreatment with the EAA receptor antagonists gamma-D-glutamylglycine (DGG) (2, 20, 200 micrograms i.c.v.) and (-)-2-amino-7-phosphonoheptanoic acid (D-APH), but not L-APH (25 micrograms i.c.v.). In chronically morphine-treated rats (25 micrograms/h i.c.v., 5 days), naloxone challenge (1 mg/kg i.v.) produced a significant increase in CA.OC signal, peak 466.5 +/- 112.7% of baseline. This naloxone-induced response was attenuated by pretreatment with DGG (200 micrograms i.c.v.) or D-APH (25 micrograms i.c.v.). To the extent that CA.OC reflects locus coeruleus neuronal activity, the present findings further suggest that increases in locus coeruleus activity during naloxone precipitated withdrawal after both acute and chronic morphine treatment are mediated at least in part by activation of EAA pathways. PMID:8221081

  13. Treatment of acute opioid withdrawal with ibogaine.

    PubMed

    Alper, K R; Lotsof, H S; Frenken, G M; Luciano, D J; Bastiaans, J

    1999-01-01

    Ibogaine is an alkaloid with putative effect in acute opioid withdrawal. Thirty-three cases of treatments for the indication of opioid detoxification performed in non-medical settings under open label conditions are summarized involving an average daily use of heroin of .64 +/- .50 grams, primarily by the intravenous route. Resolution of the signs of opioid withdrawal without further drug seeking behavior was observed within 24 hours in 25 patients and was sustained throughout the 72-hour period of posttreatment observation. Other outcomes included drug seeking behavior without withdrawal signs (4 patients), drug abstinence with attenuated withdrawal signs (2 patients), drug seeking behavior with continued withdrawal signs (1 patient), and one fatality possibly involving surreptitious heroin use. The reported effectiveness of ibogaine in this series suggests the need for systematic investigation in a conventional clinical research setting. PMID:10506904

  14. Inpatient alcohol withdrawal syndrome.

    PubMed

    Monte-Secades, R; Rabuñal-Rey, R; Guerrero-Sande, H

    2015-03-01

    A 55-year-old man was admitted for a femur fracture; an alcohol fetor was noted on admission. The following day, the patient began to experience tremors and nervousness. Intravenous haloperidol was administered. Shortly afterwards, the patient experienced two generalized seizures and then began to experience delirium and uncontrollable agitation. The patient was diagnosed with alcohol withdrawal syndrome; high doses of intravenous midazolam were prescribed and infused. A few hours later, the patient presented signs of respiratory depression, requiring a transfer to the intensive care unit. After a review of the medical history, it was determined that the patient had been admitted on 3 previous occasions due to alcohol withdrawal and had progressed to delirium tremens after experiencing seizures. Can the risk of alcohol withdrawal syndrome and the need for prophylactic treatment be assessed on admission? Were appropriate monitoring and treatment measures employed? Would it have been possible to change his outcome? PMID:25559647

  15. Hydrogen sulfide inhibits opioid withdrawal-induced pain sensitization in rats by down-regulation of spinal calcitonin gene-related peptide expression in the spine.

    PubMed

    Yang, Hai-Yu; Wu, Zhi-Yuan; Bian, Jin-Song

    2014-09-01

    Hyperalgesia often occurs in opioid-induced withdrawal syndrome. In the present study, we found that three hourly injections of DAMGO (a μ-opioid receptor agonist) followed by naloxone administration at the fourth hour significantly decreased rat paw nociceptive threshold, indicating the induction of withdrawal hyperalgesia. Application of NaHS (a hydrogen sulfide donor) together with each injection of DAMGO attenuated naloxone-precipitated withdrawal hyperalgesia. RT-PCR and Western blot analysis showed that NaHS significantly reversed the gene and protein expression of up-regulated spinal calcitonin gene-related peptide (CGRP) in naloxone-treated animals. NaHS also inhibited naloxone-induced cAMP rebound and cAMP response element-binding protein (CREB) phosphorylation in rat spinal cord. In SH-SY5Y neuronal cells, NaHS inhibited forskolin-stimulated cAMP production and adenylate cyclase (AC) activity. Moreover, NaHS pre-treatment suppressed naloxone-stimulated activation of protein kinase C (PKC) α, Raf-1, and extracellular signal-regulated kinase (ERK) 1/2 in rat spinal cord. Our data suggest that H2S prevents the development of opioid withdrawal-induced hyperalgesia via suppression of synthesis of CGRP in spine through inhibition of AC/cAMP and PKC/Raf-1/ERK pathways. PMID:24824948

  16. Cocaine withdrawal

    MedlinePlus

    Cocaine withdrawal occurs when someone who has used a lot of cocaine cuts down or quits taking the drug. Symptoms ... even if the user is not completely off cocaine and still has some of the drug in ...

  17. Formation of aversive memories associated with conditioned drug withdrawal requires BDNF expression in the amygdala in acute morphine-dependent rats

    PubMed Central

    Ju, Yun-yue; Long, Jian-dong; Liu, Yao; Liu, Jing-gen

    2015-01-01

    Aim: Brain-derived neurotrophic factor (BDNF) plays an important role in learning and memory in multiple brain areas. In the present study, we investigated the roles of BDNF in aversive memories associated with conditioned drug withdrawal in acute morphine-dependent rats. Methods: Conditioned place aversion (CPA) was induced in male SD rats exposed to a single dose of morphine (10 mg/kg, sc) followed by naloxone (0.3 mg/kg, sc). In some rats, BDNF receptor antagonist K252a (8.5 ng per side) or BDNF scavenger TrkB-FC (0.65 μg per side) was bilaterally microinjected into amygdala before naloxone injection. BDNF mRNA and protein expression levels in amygdala were detected after the behavior testing. Results: CPA behavior was induced in rats by the naloxone-precipitated morphine withdrawal, which was accompanied by significantly increased levels of BDNF mRNA and protein in the amygdala. Bilateral microinjection of TrkB-FC or K252a into the amygdala completely blocked CPA behavior in the rats. Conclusion: Formation of aversive memories associated with conditioned drug withdrawal in acute morphine-dependent rats requires BDNF expression in the amygdala. PMID:26567727

  18. Nicotine Withdrawal

    PubMed Central

    McLaughlin, Ian; Dani, John A.; De Biasi, Mariella

    2015-01-01

    An aversive abstinence syndrome manifests 4–24 h following cessation of chronic use of nicotine-containing products. Symptoms peak on approximately the 3rd day and taper off over the course of the following 3–4 weeks. While the severity of withdrawal symptoms is largely determined by how nicotine is consumed, certain short nucleotide polymorphisms (SNPs) have been shown to predispose individuals to consume larger amounts of nicotine more frequently—as well as to more severe symptoms of withdrawal when trying to quit. Additionally, rodent behavioral models and transgenic mouse models have revealed that specific nicotinic acetylcholine receptor (nAChR) subunits, cellular components, and neuronal circuits are critical to the expression of withdrawal symptoms. Consequently, by continuing to map neuronal circuits and nAChR subpopulations that underlie the nicotine withdrawal syndrome—and by continuing to enumerate genes that predispose carriers to nicotine addiction and exacerbated withdrawal symptoms—it will be possible to pursue personalized therapeutics that more effectively treat nicotine addiction. PMID:25638335

  19. Pleiotrophin modulates morphine withdrawal but has no effects on morphine-conditioned place preference.

    PubMed

    Gramage, Esther; Vicente-Rodríguez, Marta; Herradón, Gonzalo

    2015-09-14

    Pleiotrophin (PTN) is a neurotrophic factor with important functions in addiction and neurodegenerative disorders. Morphine administration induces an increase in the expression of PTN and Midkine (MK), the only other member of this family of cytokines, in brain areas related with the addictive effects of drug of abuse, like the Ventral Tegmental Area or the hippocampus. In spite of previous studies showing that PTN modulates amphetamine and ethanol rewarding effects, and that PTN is involved in morphine-induced analgesia, it was still unknown if the rewarding effects of morphine may be regulated by endogenous PTN. Thus, we aim to study the role of PTN in the reward and physical dependence induced by morphine. We used the Conditioned Place Preference (CPP) paradigm in PTN genetically deficient (PTN-/-) and wild type (WT) mice to assess the rewarding effects of morphine in absence of endogenous PTN. Second, to study if PTN may be involved in morphine physical dependence, naloxone-precipitated withdrawal syndrome was induced in PTN-/- and WT morphine dependent mice. Although the increase in the time spent in the morphine-paired compartment after conditioning tended to be more pronounced in PTN-/- mice, statistical significance was not achieved. The data suggest that PTN does not exert an important role in morphine reward. However, our results clearly indicate that PTN-/- mice develop a more severe withdrawal syndrome than WT mice, characterized as a significant increase in the time standing and in the total incidences of forepaw licking, forepaw tremors, wet dog shake and writhing. The data presented here suggest that PTN is a novel genetic factor that plays a role in morphine withdrawal syndrome. PMID:26222257

  20. Opiate and opioid withdrawal

    MedlinePlus

    ... opiate withdrawal; Oxycontin - opiate withdrawal; Hydrocodone - opiate withdrawal; Detox - opiates; Detoxification - opiates ... facilities set up to help people with detoxification (detox). In a regular hospital, if symptoms are severe. ...

  1. Opiate and opioid withdrawal

    MedlinePlus

    ... Oxycontin - opiate withdrawal; Hydrocodone - opiate withdrawal; Detox - opiates; Detoxification - opiates ... Using facilities set up to help people with detoxification (detox). In a regular hospital, if symptoms are ...

  2. New mechanisms and perspectives in nicotine withdrawal

    PubMed Central

    Jackson, K.J.; Muldoon, P.P.; De Biasi, M.; Damaj, M.I.

    2014-01-01

    Diseases associated with tobacco use constitute a major health problem worldwide. Upon cessation of tobacco use, an unpleasant withdrawal syndrome occurs in dependent individuals. Avoidance of the negative state produced by nicotine withdrawal represents a motivational component that promotes continued tobacco use and relapse after smoking cessation. With the modest success rate of currently available smoking cessation therapies, understanding mechanisms involved in the nicotine withdrawal syndrome are crucial for developing successful treatments. Animal models provide a useful tool for examining neuroadaptative mechanisms and factors influencing nicotine withdrawal, including sex, age, and genetic factors. Such research has also identified an important role for nicotinic receptor subtypes in different aspects of the nicotine withdrawal syndrome (e.g., physical vs. affective signs). In addition to nicotinic receptors, the opioid and endocannabinoid systems, various signal transduction pathways, neurotransmitters, and neuropeptides have been implicated in the nicotine withdrawal syndrome. Animal studies have informed human studies of genetic variants and potential targets for smoking cessation therapies. Overall, the available literature indicates that the nicotine withdrawal syndrome is complex, and involves a range of neurobiological mechanisms. As research in nicotine withdrawal progresses, new pharmacological options for smokers attempting to quit can be identified, and treatments with fewer side effects that are better tailored to the unique characteristics of patients may become available. PMID:25433149

  3. 29 CFR 4219.11 - Withdrawal liability upon mass withdrawal.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 29 Labor 9 2010-07-01 2010-07-01 false Withdrawal liability upon mass withdrawal. 4219.11 Section... Redetermination of Withdrawal Liability Upon Mass Withdrawal § 4219.11 Withdrawal liability upon mass withdrawal. (a) Initial withdrawal liability. The plan sponsor of a multiemployer plan that experiences a...

  4. 29 CFR 4219.11 - Withdrawal liability upon mass withdrawal.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 29 Labor 9 2011-07-01 2011-07-01 false Withdrawal liability upon mass withdrawal. 4219.11 Section... Redetermination of Withdrawal Liability Upon Mass Withdrawal § 4219.11 Withdrawal liability upon mass withdrawal. (a) Initial withdrawal liability. The plan sponsor of a multiemployer plan that experiences a...

  5. 29 CFR 4219.11 - Withdrawal liability upon mass withdrawal.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 29 Labor 9 2013-07-01 2013-07-01 false Withdrawal liability upon mass withdrawal. 4219.11 Section... Redetermination of Withdrawal Liability Upon Mass Withdrawal § 4219.11 Withdrawal liability upon mass withdrawal. (a) Initial withdrawal liability. The plan sponsor of a multiemployer plan that experiences a...

  6. 29 CFR 4219.11 - Withdrawal liability upon mass withdrawal.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 29 Labor 9 2012-07-01 2012-07-01 false Withdrawal liability upon mass withdrawal. 4219.11 Section... Redetermination of Withdrawal Liability Upon Mass Withdrawal § 4219.11 Withdrawal liability upon mass withdrawal. (a) Initial withdrawal liability. The plan sponsor of a multiemployer plan that experiences a...

  7. 29 CFR 4219.11 - Withdrawal liability upon mass withdrawal.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 29 Labor 9 2014-07-01 2014-07-01 false Withdrawal liability upon mass withdrawal. 4219.11 Section... Redetermination of Withdrawal Liability Upon Mass Withdrawal § 4219.11 Withdrawal liability upon mass withdrawal. (a) Initial withdrawal liability. The plan sponsor of a multiemployer plan that experiences a...

  8. Vital Signs

    MedlinePlus

    Your vital signs show how well your body is functioning. They are usually measured at doctor's offices, often as part ... be a sign of a serious breathing problem. Temperature, which measures how hot your body is. A ...

  9. Warning Signs.

    ERIC Educational Resources Information Center

    Our Children, 1999

    1999-01-01

    Presents various signs that may indicate emotional problems in children or teens, noting that if children exhibit any of the warning signs, it is important to talk to a doctor, counselor, or mental-health professional. The warning signs are categorized as things that trouble the child, things that limit the child, behavior problems, and sudden…

  10. Adenosine kinase inhibitors attenuate opiate withdrawal via adenosine receptor activation.

    PubMed

    Kaplan, G B; Coyle, T S

    1998-11-27

    Previous studies have demonstrated a role for adenosine in mediating opiate effects. This study examines the effects of indirect activation of adenosine receptors, via treatment with adenosine kinase inhibitors, on the expression of opiate withdrawal in mice. Mice receive chronic morphine treatment via implantation of subcutaneous morphine pellets (75 mg) for 72 h. Mice then receive parenteral treatment with adenosine kinase inhibitors, either 5'-amino-5'-deoxyadenosine (2, 5, 20, 40 mg/kg, intraperitoneal or i.p.) or iodotubericidin (1, 2, 5 mg/kg, i.p.), followed by naloxone injection and opiate withdrawal signs are measured over 20 min. Both adenosine kinase inhibitors significantly reduce the following opiate withdrawal signs in a dose-dependent manner compared to vehicle: withdrawal jumps, teeth chattering, forepaw tremors, and forepaw treads. Additionally, 5'-amino-5'-deoxyadenosine significantly reduces withdrawal-induced diarrhea and weight loss. Effects of 5'-amino-5'-deoxyadenosine (40 mg/kg) on opiate withdrawal signs appear to be mediated via adenosine receptor activation as they are reversed by pretreatment by adenosine receptor antagonist caffeine (20 mg, i.p.) but not by selective phosphodiesterase inhibitor Ro 20-1724 (10 mg/kg, i.p.). Adenosine receptor activation via adenosine kinase inhibitor treatment attenuates opiate withdrawal and these agents may be generally useful in the treatment of drug withdrawal syndromes. PMID:9865523

  11. Vital Signs

    MedlinePlus

    Your vital signs show how well your body is functioning. They are usually measured at doctor's offices, often as part ... standing, which medicines you take, and your weight. Respiratory rate, which measures your breathing. Mild breathing changes can ...

  12. Cyclosporine alters opiate withdrawal in rodents.

    PubMed

    Dafny, N; Wagle, V G; Drath, D B

    1985-05-01

    Opiates exert numerous effects on all levels of the central nervous system with tolerance, physical dependence and withdrawal being characteristics of this drug class. The degree of dependence is directly correlated to the intensity of withdrawal. Therefore, success in modifying the withdrawal syndrome may shed light on the dynamics of opiate addiction. The present study demonstrates that cyclosporine, a widely used immunosuppressive drug, considerably modified the behavioral signs of a naloxone-induced abstinence syndrome in morphine-addicted rats. In previous experiments, alpha-interferon has shown similar results. The similarity in actions of these two immunomodulator drugs is discussed and we suggest that opiate addiction may involve the immune system. PMID:4039025

  13. Withdrawal strategies for outpatients

    PubMed Central

    Mezciems, Edgar

    1996-01-01

    This article discusses outpatient withdrawal strategies for patients addicted to alcohol, benzodiazepines, barbiturates, and opiates and describes some practical ways to support recovery. PMID:8828877

  14. Vital Signs.

    ERIC Educational Resources Information Center

    Brown, Lester R.

    1993-01-01

    Presents an excerpt from the first edition of Vital Signs, a Worldwide Institute publication that provides an annual update on global environmental trends. Includes discussion of the dismantling of nuclear arms, reduction in chlorofluorocarbon production, growth in bicycle production, the decline in cigarette smoking, and decline in military…

  15. Role of central histaminergic system in lorazepam withdrawal syndrome in rats.

    PubMed

    Nath, C; Gupta, M B

    2001-04-01

    Effects of histaminergic agonists and antagonists were investigated on withdrawal signs in lorazepam-dependent rats. Physical dependence was developed by giving lorazepam admixed with the food in the following dose schedule (in mg/kg given daily x days): 10 x 4, 20 x 4, 40 x 4, 80 x 4, and 120 x 7. The parameters observed during the periods of administration of lorazepam and after its withdrawal were spontaneous locomotor activity (SLA), reaction time to pain, foot shock aggression (FSA), and audiogenic seizures. During the withdrawal period, the rats were divided into groups of 10 each. Control-withdrawal group did not receive any drug. The drugs (in mg/kg administered intramuscularly)--L-histidine (50), histamine-N-methyl (2), promethazine (10), pheniramine (10), astemizole (10), and thioperamide (1)--were given separately in other groups daily during the withdrawal period. The withdrawal signs in control group were hyperkinesia, hyperaggression, and audiogenic seizures. L-Histidine, precursor of histamine, and thioperamide, antagonist of H3 receptor, potentiated hyperkinesia, hyperaggression, and audiogenic seizures. Histamine-N-methyl, agonist of H3 receptor, and H1 receptor antagonists, promethazine and pheniramine, blocked all the withdrawal signs. Astemizole, a peripheral antagonist of H1 receptor, could not affect any withdrawal sign. It may be concluded that histamine H1 receptors are facilitatory and H3 receptors are inhibitory for benzodiazepine (BZD) withdrawal syndrome. PMID:11526976

  16. Chronic agmatine treatment prevents behavioral manifestations of nicotine withdrawal in mice.

    PubMed

    Kotagale, Nandkishor R; Chopde, Chandrabhan T; Umekar, Milind J; Taksande, Brijesh G

    2015-05-01

    Smoking cessation exhibits an aversive withdrawal syndrome characterized by both increases in somatic signs and affective behaviors including anxiety and depression. In present study, abrupt withdrawal of daily nicotine injections (2mg/kg, s.c., four times daily, for 10 days) significantly increased somatic signs viz. rearing, grooming, jumping, genital licking, leg licking, head shakes with associated depression (increased immobility in forced swim test) as well as anxiety (decreased the number of entries and time spent in open arm in elevated plus maze) in nicotine dependent animals. The peak effect was observed at 24h time point of nicotine withdrawal. Repeated administration of agmatine (40-80µg/mouse, i.c.v.) before the first daily dose of nicotine from day 5 to 10 attenuated the elevated scores of somatic signs and abolished the depression and anxiety like behavior induced by nicotine withdrawal in dependent animals. However, in separate groups, its acute administration 30min before behavior analysis of nicotine withdrawal was ineffective. This result clearly shows the role of agmatine in development of nicotine dependence and its withdrawal. In extension to behavioral experiments, brain agmatine analyses, carried out at 24h time point of nicotine withdrawal demonstrated marked decrease in basal brain agmatine concentration as compared to control animals. Taken together, these data support the role of agmatine as common biological substrate for somatic signs and affective symptoms of nicotine withdrawal. This data may project therapies based on agmatine in anxiety, depression and mood changes associated with tobacco withdrawal. PMID:25744879

  17. Insomnia related to biperiden withdrawal in two schizophrenic patients.

    PubMed

    Hirose, S

    2000-11-01

    It is not uncommon for patients who are receiving antipsychotic medication to be given anticholinergic agents, such as biperiden, despite the relative absence of neurological side-effects. Two cases of schizophrenia are reported in which insomnia developed after biperiden withdrawal or reduction. The insomnia continued until biperiden treatment was reinstated, despite the fact that the patients did not exhibit signs or report symptoms indicative of antipsychotic drug-induced neurological side-effects. The occurrence of insomnia following the withdrawal of biperiden or reduction in the dose has not been previously reported. One potential explanation for the insomnia is cholinergic rebound following the withdrawal of biperiden. PMID:11110012

  18. Freshwater withdrawals in Texas, 1985

    USGS Publications Warehouse

    Lurry, Dee L.; Barber, Nancy L.

    1990-01-01

    Freshwater withdrawal data was compiled for the 254 counties in Texas for 1985. Major categories of withdrawal are presented by county on maps of the State. Withdrawals are also shown by source, aquifer, and major river basin. Total freshwater withdrawals in Texas during 1985 were about 20, 100 million gal/day. Surface-water withdrawals were about 12,900 million gal/day or 64% of the total, and groundwater withdrawals were about 7,190 million gal/day or 36% of the total. More water was withdrawn for irrigation than for any other purpose, accounting for 40% of total freshwater withdrawals and for 75% of groundwater withdrawals. (USGS)

  19. [Clozapine withdrawal. A review].

    PubMed

    Szafrański, T; Gmurkowski, K

    1999-01-01

    The article describes the symptoms of withdrawal of clozapine and their possible causes as well as research on switching from clozapine to another antipsychotic drug. A computerised search was conducted using MEDLINE (1966-1997) to retrieve reports of clozapine withdrawal. Fifteen case reports and sixteen withdrawal studies (only one of them double-blind and two single-blind) were identified. Clozapine multi-receptors profile seems to be responsible for withdrawal symptoms--several specific mechanisms are suggested: cholinergic supersensitivity, dopaminergic supersensivity, special role of D4 receptors, possibilities of serotonergic, noradrenergic and GABA-ergic involvement. Risk of relapse after withdrawal of clozapine seems to be greater than after withdrawal of classical neuroleptics. Some patients might become de novo neuroleptic resistant for at least several weeks after withdrawal. Therefore, clozapine should be stopped only due to strong clinical indications, and if only possible, the withdrawal should be slow (50 mg/week). To prevent relapse of psychosis some experts advocate starting new antipsychotic drugs in therapeutic dosage before withdrawal of clozapine is completed. In case of emergency, when clozapine (high dosage) must be withdrawn immediately, patient must be hospitalised and cholinergics might be considered to prevent, cholinergic rebound". There are no established guidelines which antipsychotic to choose after withdrawal of clozapine. In general, classical antipsychotics are ineffective. Thioridazine is suggested because of its prominent anticholinergic activity, but there is no clinical evidence of advantage of this treatment in comparison to classical drugs. Risperidon and especially olanzapine are promising possibilities, but initial data are disappointing. Benzamides might be another possibility but clinical data are scarce. These important issues require further studies. PMID:10786215

  20. [Reverse Chaddock sign].

    PubMed

    Tashiro, Kunio

    2011-08-01

    It is widely accepted that the Babinski reflex is the most well-known and important pathological reflex in clinical neurology. Among many other pathological reflexes that elicit an upgoing great toe, such as Chaddock, Oppenheim, Gordon, Schaefer, and Stransky, only the Chaddock reflex is said to be as sensitive as the Babinski reflex. The optimal receptive fields of the Babinski and Chaddock reflexes are the lateral plantar surface and the external inframalleolar area of the dorsum, respectively. It has been said that the Babinski reflex, obtained by stroking the sole, is by far the best and most reliable method of eliciting an upgoing great toe. However, the Chaddock reflex, the external malleolar sign, is also considered sensitive and reliable according to the literature and everyday neurological practice. The major problems in eliciting the Babinski reflex by stroking the lateral part of the sole are false positive or negative responses due to foot withdrawal, tonic foot response, or some equivocal movements. On the other hand, according to my clinical experience, the external inframalleolar area, which is the receptive field of the Chaddock reflex, is definitely suitable for eliciting the upgoing great toe. In fact, the newly proposed method to stimulate the dorsum of the foot from the medial to the lateral side, which I term the "reversed Chaddock method," is equally sensitive to demonstrate pyramidal tract involvement. With the "reversed Chaddock method", the receptive field of the Chaddock reflex may be postulated to be in the territory of the sural nerve, which could be supported by the better response obtained on stimulation of the postero-lateral calf than the anterior shin. With regard to the receptive fields of the Babinski and Chaddock reflexes, the first sacral dermatome (S1) is also considered a reflexogenous zone, but since the dermatome shows marked overlapping, the zones vary among individuals. As upgoing toe responses are consistently observed in

  1. Affective and Neuroendocrine Effects of Withdrawal from Chronic, Long-Acting Opiate Administration

    PubMed Central

    Hamilton, Kathryn L.; Harris, Andrew C.; Gewirtz, Jonathan C.

    2013-01-01

    Although the long-acting opiate methadone is commonly used to treat drug addiction, relatively little is known about effects of withdrawal from this drug in preclinical models. The current study examined affective, neuroendocrine, and somatic signs of withdrawal from the longer-acting methadone derivative l-alpha-acetylmethydol (LAAM) in rats. Anxiety-like behavior during both spontaneous and antagonist-precipitated withdrawal was measured by potentiation of the startle reflex. Withdrawal elevated corticosterone and somatic signs and blunted circadian variations in baseline startle responding. In addition, fear to an explicit, Pavlovian conditioned stimulus (fear-potentiated startle) was enhanced. These data suggest that anxiety-like behavior as measured using potentiated startle responding does not emerge spontaneously during withdrawal from chronic opiate exposure – in contrast to withdrawal from acute drug exposure – but rather is manifested as exaggerated fear in response to explicit threat cues. PMID:24076207

  2. 48 CFR 14.304 - Submission, modification, and withdrawal of bids.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... ACQUISITION REGULATION CONTRACTING METHODS AND CONTRACT TYPES SEALED BIDDING Submission of Bids 14.304... withdrawal is established and the person signs a receipt for the bid. Upon withdrawal of an electronically..., unless contract award is imminent and the notices prescribed in 14.409 would suffice. (g) Late bids...

  3. Withdrawing Nutrition, Hydration

    Cancer.gov

    Module eleven of the EPEC-O Self-Study Original Version discusses the general aspects of withholding or withdrawing of life-sustaining therapies, and presents a specific application to artificial nutrition and hydration.

  4. Diazepam withdrawal syndrome: its prolonged and changing nature.

    PubMed Central

    Mellor, C. S.; Jain, V. K.

    1982-01-01

    The diazepam withdrawal syndrome was studied in 10 patients who had abused the drug for 3 to 14 years. In the previous 6 months their consumption of diazepam had ranged from 60 to 120 mg daily; none had used other drugs during this period. The withdrawal period lasted about 6 weeks. The intensity of the symptoms and signs was high initially, fell during the first 2 weeks, then rose again in the third week, before finally declining. Three groups of symptoms and signs were identified. Group A symptoms occurred throughout withdrawal and included tremor, anorexia, insomnia and myoclonus. Group B symptoms and signs were largely confined to the first 10 days and were those of a toxic psychosis. Group C symptoms reached a peak in the third and fourth weeks of withdrawal and were characterized by sense perceptions that were either heightened or lowered. The symptom groups, the presence of tremor and myoclonus, and the relief of symptoms by a test dose permit diazepam withdrawal to be distinguished from anxiety. The biphasic course of the symptoms is probably related to the pharmacokinetics of diazepam. PMID:7139456

  5. Role of adenosine A1 and A2A receptors in the alcohol withdrawal syndrome.

    PubMed

    Kaplan, G B; Bharmal, N H; Leite-Morris, K A; Adams, W R

    1999-10-01

    The role of adenosine receptor-mediated signaling was examined in the alcohol withdrawal syndrome. CD-1 mice received a liquid diet containing ethanol (6.7%, v/v) or a control liquid diet that were abruptly discontinued after 14 days of treatment. Mice consuming ethanol showed a progressive increase in signs of intoxication throughout the drinking period. Following abrupt discontinuation of ethanol diet, mice demonstrated reversible signs of handling-induced hyperexcitability that were maximal between 5-8 h. Withdrawing mice received treatment with adenosine receptor agonists at the onset of peak withdrawal (5.5 h) and withdrawal signs were blindly rated (during withdrawal hours 6 and 7). Adenosine A1-receptor agonist R-N6(phenylisopropyl)adenosine (0.15 and 0.3 mg/ kg) reduced withdrawal signs 0.5 and 1.5 h after drug administration in a dose-dependent fashion. Adenosine A2A-selective agonist 2-p-(2-carboxyethyl)phenylethyl-amino-5'-N-ethylcarboxamidoadenosine (0.3 mg/kg) reduced withdrawal signs at both time points. In ethanol-withdrawing mice, there were significant decreases in adenosine transporter sites in striatum without changes in cortex or cerebellum. In ethanol-withdrawing mice, there were no changes in adenosine A1 and A2A receptor concentrations in cortex, striatum, or cerebellum. There appears to be a role for adenosine A1 and A2A receptors in the treatment of the ethanol withdrawal syndrome. Published by Elsevier Science Inc. PMID:10548160

  6. Stroke Warning Signs

    MedlinePlus

    ... News Advocate Stroke Warning Signs Quiz Stroke Warning Signs and Symptoms THINK YOU ARE HAVING A STROKE? ... Learn more stroke signs and symptoms >>>> Stroke Warning Signs Hip-Hop F.A.S.T. Video Updated Guidelines ...

  7. Headaches - danger signs

    MedlinePlus

    Migraine headache - danger signs; Tension headache - danger signs; Cluster headache - danger signs; Vascular headache - danger signs ... and bleeding in the brain can cause a headache. These problems include: Abnormal connection between the arteries ...

  8. Signing off

    NASA Astrophysics Data System (ADS)

    2001-05-01

    sharp that they cause paper cuts. Stains. If you accidentally spill some food or drink on your clothes, make sure you attempt to remove it as soon as possible and preferably within the same lunar cycle. Some teachers seem to think they should be worn with pride like the stains on a chemistry teacher's white coat. This is a myth. Materials. For scientists continually teaching about the wonder of smart materials, physics teachers are remarkably conservative in their choice of materials for their clothes. Try to break out from the traditional corduroy and tweed and practise what you teach. It is not acceptable to wear the actual tie you wore at school, as this will be at least 20 years old, be rather frayed and will have your name sewn in the back by your mum. Steven Chapman Science Year Manager, British Association for the Advancement of Science Signing Off takes a humorous and irreverent look at physics education. The views expressed here are those of the author and are not endorsed by the Editorial Board for Physics Education. Can you contribute a zany attitude or humorous anecdote? Please send your offering to ped@iop.org marked Signing Off.

  9. The alcohol withdrawal syndrome.

    PubMed

    McKeon, A; Frye, M A; Delanty, Norman

    2008-08-01

    The alcohol withdrawal syndrome (AWS) is a common management problem in hospital practice for neurologists, psychiatrists and general physicians alike. Although some patients have mild symptoms and may even be managed in the outpatient setting, others have more severe symptoms or a history of adverse outcomes that requires close inpatient supervision and benzodiazepine therapy. Many patients with AWS have multiple management issues (withdrawal symptoms, delirium tremens, the Wernicke-Korsakoff syndrome, seizures, depression, polysubstance abuse, electrolyte disturbances and liver disease), which requires a coordinated, multidisciplinary approach. Although AWS may be complex, careful evaluation and available treatments should ensure safe detoxification for most patients. PMID:17986499

  10. Alcohol Abuse: Alcohol Withdrawal Syndrome

    MedlinePlus

    ... they quit drinking. What are the symptoms of alcohol withdrawal syndrome? Symptoms can be mild or severe, and may include: Shakiness Sweats Anxiety Irritability Fatigue Depression Headaches Insomnia Nightmares Decreased appetite More severe withdrawal symptoms ...

  11. Cullen Sign and Grey Turner Sign Revisited.

    PubMed

    Wright, William F

    2016-06-01

    Cullen sign and Grey Turner sign, named after Thomas Stephen Cullen, MB, and George Grey Turner, MBBS, respectively, are signs of abdominal wall hemorrhage and are generally associated with acute pancreatitis. However, the research from which these signs arose was documented long before Cullen and Grey Turner made their contributions. The present article examines the history, pathologic mechanisms, and clinical application of these signs in relation to acute pancreatitis and ectopic pregnancy. PMID:27214777

  12. Signing off

    NASA Astrophysics Data System (ADS)

    2001-09-01

    Physics Related Aptitude Test As the teacher shortage bites anyone with a degree in science expects to walk into a school and be received, with open arms, as a physics teacher. Are they really suitable? To help you decide Signing Off provides the following invaluable psychometric test. Extensively researched and, for single users only, it comes completely free to Physics Education subscribers! (Copies of this Physics Related Aptitude Test are available to credit-card customers from prat@realripoff.com priced #35 per client, 125 dollars to US customers.) This invaluable psychometric test has been extensively researched. Your first lesson of the new school year introduces the study of electricity. Do you: A Use the notes prepared by your predecessor. B Find a video on electricity and play it to the class. C Arrange a series of exciting practical demonstrations to stimulate the young inquiring mind. D Let the children design and make their own circuits to light flashlight bulbs. Your 14-year-olds have completed a written test on heat and energy. Do you: A Mark correct only the work of students who have written their names neatly at the top LEFT HAND corner, as required. B Only set multiple choice tests, so that the computer can mark them for you. C Mark carefully by hand, explaining in detail to each student exactly how and why they have made errors and adding encouraging comments with lots of praise. D Give out correct sets of answers and allow students to mark their own work. There is a staff social. Do you: A Ask for a definition of the term 'social'. B Ask for a web-based version. C Determine to go, so that you can discuss setting up cross-curricular links with colleagues. D Join the organizing committee. Who do you admire most? A Sir Isaac Newton. B Bill Gates. C Leonardo da Vinci. D Leonardo di Caprio. You are required to teach biology class. Your response is: A Denial. B To ask for an appropriate computer simulation. C To attend a specialized course for biology

  13. Dual Inhibition of Endocannabinoid Catabolic Enzymes Produces Enhanced Antiwithdrawal Effects in Morphine-Dependent Mice

    PubMed Central

    Ramesh, Divya; Gamage, Thomas F; Vanuytsel, Tim; Owens, Robert A; Abdullah, Rehab A; Niphakis, Micah J; Shea-Donohue, Terez; Cravatt, Benjamin F; Lichtman, Aron H

    2013-01-01

    Inhibition of the endocannabinoid catabolic enzymes, monoacylglycerol lipase (MAGL) or fatty acid amide hydrolase (FAAH) attenuates naloxone-precipitated opioid withdrawal signs in mice via activation of CB1 receptors. Complete FAAH inhibition blocks only a subset of withdrawal signs, whereas complete MAGL inhibition elicits enhanced antiwithdrawal efficacy, but is accompanied with some cannabimimetic side effects. Thus, the primary objective of the present study was to determine whether combined, full FAAH inhibition and partial MAGL represents an optimal strategy to reduce opioid withdrawal. To test this hypothesis, we examined whether combined administration of high-dose of the FAAH inhibitor PF-3845 and low-dose of the MAGL inhibitor JZL184, as well as the novel dual FAAH-MAGL inhibitor SA-57, which is 100-fold more potent in inhibiting FAAH than MAGL, would prevent spontaneous withdrawal in morphine-dependent mice, a model with greater face validity than precipitating withdrawal with μ-opioid receptor antagonists. Strikingly, a combination of low-dose JZL184 and high-dose PF-3845 as well as the dual inhibitor SA-57 reduced all abrupt withdrawal signs (ie, platform jumping, paw flutters, head shakes, diarrhea, and total body weight loss), but did not elicit any cannabimimetic side effects. In addition, JZL184 or PF-3845 blocked naloxone-precipitated hypersecretion in morphine-dependent small intestinal tissue. Collectively, these results are the first to show that endocannabinoid catabolic enzyme inhibitors reduce abrupt withdrawal in morpine-dependent mice and are effective in a novel in vitro model of opioid withdrawal. More generally, these findings support the idea that joint MAGL and FAAH inhibition represents a promising approach for the treatment of opioid dependence. PMID:23303065

  14. Management of the patient with ESRD after withdrawal from dialysis.

    PubMed

    DeVelasco, R; Dinwiddie, L C

    1998-12-01

    When dialysis no longer achieves the goal of prolonging quality life for the ESRD patient, withdrawal from dialysis is an option. Many patients, their families, and caregivers cannot make an informed decision to withdraw because they do not have sufficient information or, worse, are misinformed about what the patient might experience. This paper reviews the clinical circumstances in which dialysis is discontinued as well as the physiological signs and symptoms of the uremic-related death. Palliative management of those symptoms is from one nephrologist's model and provides a starting point for dialogue about this necessary care. PMID:10188396

  15. Warning Signs After Birth

    MedlinePlus

    ... Pregnancy > Postpartum care > Warning signs after birth Warning signs after birth E-mail to a friend Please ... infection Postpartum bleeding Postpartum depression (PPD) What warning signs should you look for? Call your provider if ...

  16. Transitions in viscous withdrawal

    NASA Astrophysics Data System (ADS)

    Zhang, Wendy W.

    2008-11-01

    A process analogous to flow-focusing occurs in extended and stably stratified layers of immiscible, viscous liquids. In viscous withdrawal, an axisymmetric converging flow is imposed in the upper layer. When the upper layer flow is weak, the interface forms a hump. No liquid from the lower layer is entrained. When the upper layer flow is strong, liquid from the lower layer is entrained and the interface becomes a spout. Here I summarize recent results on the fundamental mechanisms controlling these regimes. For selective withdrawal, a clear picture has emerged, with good agreement between theory, simulation and experiment. The regime ends when the viscous stress exerted by the upper layer flow overcomes surface tension, creating a saddle-node bifurcation in the hump solution. Less is understood about viscous entrainment. A long-wavelength model including only local information is degenerate, possessing many solutions for the same withdrawal condition. Including information about the global geometry removes this degeneracy but also makes the surprising prediction that global geometry can change the nature of the transition. First-order, weakly first-order or continuous transitions are all possible. How these results relate to the variety of experimental phenomena, such as stable, micron-sized spouts, intricate patterns of hysteresis and multiple stable spout states under the same condition, is at present unclear. (Includes material from joint works with Blanchette, Cohen, Kleine Berkenbusch, and Schmidt.)

  17. Social Withdrawal in Childhood

    PubMed Central

    Rubin, Kenneth H.; Coplan, Robert J.; Bowker, Julie C.

    2013-01-01

    Socially withdrawn children frequently refrain from social activities in the presence of peers. The lack of social interaction in childhood may result from a variety of causes, including social fear and anxiety or a preference for solitude. From early childhood through to adolescence, socially withdrawn children are concurrently and predictively at risk for a wide range of negative adjustment outcomes, including socio-emotional difficulties (e.g., anxiety, low self-esteem, depressive symptoms, and internalizing problems), peer difficulties (e.g., rejection, victimization, poor friendship quality), and school difficulties (e.g., poor-quality teacher-child relationships, academic difficulties, school avoidance). The goals of the current review are to (a) provide some definitional, theoretical, and methodological clarity to the complex array of terms and constructs previously employed in the study of social withdrawal; (b) examine the predictors, correlates, and consequences of child and early-adolescent social withdrawal; and (c) present a developmental framework describing pathways to and from social withdrawal in childhood. PMID:18851686

  18. Social withdrawal in childhood.

    PubMed

    Rubin, Kenneth H; Coplan, Robert J; Bowker, Julie C

    2009-01-01

    Socially withdrawn children frequently refrain from social activities in the presence of peers. The lack of social interaction in childhood may result from a variety of causes, including social fear and anxiety or a preference for solitude. From early childhood through to adolescence, socially withdrawn children are concurrently and predictively at risk for a wide range of negative adjustment outcomes, including socio-emotional difficulties (e.g., anxiety, low self-esteem, depressive symptoms, and internalizing problems), peer difficulties (e.g., rejection, victimization, poor friendship quality), and school difficulties (e.g., poor-quality teacher-child relationships, academic difficulties, school avoidance). The goals of the current review are to (a) provide some definitional, theoretical, and methodological clarity to the complex array of terms and constructs previously employed in the study of social withdrawal; (b) examine the predictors, correlates, and consequences of child and early-adolescent social withdrawal; and (c) present a developmental framework describing pathways to and from social withdrawal in childhood. PMID:18851686

  19. A 'symptom-triggered' approach to alcohol withdrawal management.

    PubMed

    Murdoch, Jay; Marsden, Janet

    In acute hospital settings, alcohol withdrawal often causes significant management problems and complicates a wide variety of concurrent conditions, placing a huge burden on the NHS. A significant number of critical incidents around patients who were undergoing detoxification in a general hospital setting led to the need for a project to implement and evaluate an evidence-based approach to the management of alcohol detoxification-a project that included a pre-intervention case note audit, the implementation of an evidence-based symptom-triggered detoxification protocol, and a post-intervention case note audit. This change in practice resulted in an average reduction of almost 60% in length of hospital stay and a 66% reduction in the amount of chlordiazepoxide used in detoxification, as well as highlighting that 10% of the sample group did not display any signs of withdrawal and did not require any medication. Even with these reductions, no patient post-intervention developed any severe signs of withdrawal phenomena, such as seizures or delirium tremens. The savings to the trust (The Pennine Acute Hospital Trust) are obvious,but the development of a consistent, quality service will lead to fewer long-term negative effects for patients that can be caused by detoxification. This work is a project evaluation of a locally implemented strategy, which, it was hypothesised,would improve care by providing an individualised treatment plan for the management of alcohol withdrawal symptoms. PMID:24809146

  20. Presumed Pseudotumor Cerebri Syndrome After Withdrawal of Inhaled Glucocorticoids.

    PubMed

    Kwon, Young Joon; Allen, Julian L; Liu, Grant T; McCormack, Shana E

    2016-06-01

    Pseudotumor cerebri syndrome (PTCS) is characterized by increased intracranial pressure with normal brain parenchyma and cerebrospinal fluid constituents. PTCS after withdrawal of systemic corticosteroids also has been described in children. In contrast, to our knowledge, PTCS after withdrawal of inhaled glucocorticoids has not previously been described. Here we report the case of an 8-year and 6-month-old girl who developed signs and symptoms consistent with PTCS after withdrawal of inhaled glucocorticoids. The patient had excellent adherence to inhaled glucocorticoid therapy for ∼1 year before presentation, after which the therapy was stopped for concern related to poor growth. The withdrawal of inhaled glucocorticoids was associated with the development of severe headaches and diplopia, and further clinical examination led to the patient's diagnosis of likely PTCS. Although its occurrence is likely rare, clinicians caring for the many children receiving inhaled glucocorticoid therapy should be aware of the potential for PTCS after abrupt withdrawal of such treatment, and consider ophthalmology evaluation if patients report suggestive symptoms, such as headaches or vision changes in this context. PMID:27244842

  1. Cannabinoid withdrawal in mice: inverse agonist vs neutral antagonist

    PubMed Central

    Tai, Sherrica; Nikas, Spyros P.; Shukla, Vidyanand G.; Vemuri, Kiran; Makriyannis, Alexandros; Järbe, Torbjörn U.C.

    2015-01-01

    Rationale Previous reports shows rimonabant's inverse properties may be a limiting factor for treating cannabinoid dependence. To overcome this limitation neutral antagonists were developed, to address mechanisms by which an inverse agonist and neutral antagonist elicit withdrawal. Objective Introduces an animal model to study cannabinoid dependence by incorporating traditional methodologies and profiling novel cannabinoid ligands with distinct pharmacological properties/modes of action by evaluating their pharmacological effects on CB1-receptor (CB1R) related physiological/behavioral endpoints. Methods The cannabinergic AM2389 was acutely characterized in the tetrad (locomotor activity, analgesia, inverted screen/catalepsy bar test and temperature); with some comparisons made to Δ9-tetrahydrocannabinol (THC). Tolerance was measured in mice repeatedly administered AM2389. Antagonist-precipitated withdrawal was characterized in cannabinoid-adapted mice induced by either centrally acting antagonists, rimonabant and AM4113, or an antagonist with limited brain penetration, AM6545. Results In the tetrad, AM2389 was more potent and longer acting than THC, suggesting a novel approach for inducing dependence. Repeated administration of AM2389 led to tolerance by attenuating hypothermia that was induced by acute AM2389 administration. Antagonist-precipitated withdrawal signs were induced by rimonabant or AM4113, but not by AM6545. Antagonist-precipitated withdrawal was reversed by reinstating AM2389 or THC. Conclusions These findings suggest cannabinoid-precipitated withdrawal may not be ascribed to the inverse properties of rimonabant, but rather to rapid competition with the agonist at the CB1R. This withdrawal syndrome is likely centrally-mediated, since only the centrally acting CB1R antagonists elicited withdrawal, i.e., such responses were absent after the purported peripherally selective CB1R antagonist AM6545. PMID:25772338

  2. Morphine withdrawal dramatically reduces lymphocytes in morphine-dependent macaques.

    PubMed

    Weed, Michael R; Carruth, Lucy M; Adams, Robert J; Ator, Nancy A; Hienz, Robert D

    2006-09-01

    The immune effects of chronic opiate exposure and/or opiate withdrawal are not well understood. The results of human studies with opiate abusers are variable and may not be able to control for important factors such as subjects' drug histories, health and nutritional status. Nonhuman primate models are necessary to control these important factors. A model of opiate dependence in macaques was developed to study the effects of opiate dependence and withdrawal on measures of immune function. Four pigtailed macaques drank a mixture of morphine (20 mg/kg/session) and orange-flavored drink every 6 h for several months. During stable morphine dependence, absolute numbers of neutrophils, monocytes and lymphocytes did not change relative to pre-morphine levels. However, there was a significant decrease in the absolute number and percentage of natural killer (NK) cells in morphine dependence. Either precipitated withdrawal or abstinence for 24 h resulted in behavioral withdrawal signs in all animals. Absolute lymphocyte counts decreased and absolute netrophil counts increased significantly in withdrawal, relative to levels during morphine dependence. Lymphocyte subset (CD4+, CD8+, CD20+) cells were also decreased in absolute numbers with little change in their percentage distributions. There was, however, a significant increase in the percentage of NK cells in withdrawal relative to levels during morphine dependence. This study demonstrates the usefulness of voluntary oral self-dosing procedures for maintaining morphine dependence in nonhuman primates and demonstrates that the morphine withdrawal syndrome includes large alterations in blood parameters of immune system function, including nearly 50% reduction in numbers of CD4+, CD8+ and CD20+ cells. PMID:18040802

  3. Withdrawal-like effects of pentylenetetrazol and valproate in the naive organism: a model of motivation produced by opiate withdrawal?

    PubMed

    Mucha, R F; Fassos, F F; Perl, F M

    1995-07-01

    Pentylenetetrazol (PTZ) and sodium valproate (VPA) produce acutely in the naive rat various behavioural effects resembling signs of opiate withdrawal in the morphine-treated subject. Suggestions in the literature that these substances may activate directly some of the neural consequences of opiate and drug withdrawal prompted us to look for and examine possible aversive effects of these substances at non-toxic doses. With a sensitive two-flavour, three-trial taste aversion procedure, relatively low doses of PTZ and VPA (5 and 160 mg/kg, respectively) do indeed have aversive effects. The maximum aversions were produced by 10 and 20 mg/kg PTZ and 320 mg/kg VPA and were equivalent to those of morphine withdrawal precipitated by 0.01-0.03 mg/kg naloxone in a morphine pellet-implanted animal. Moreover, the maximum aversions with PTZ and VPA were significantly higher than the maximum aversions seen with naloxone in the drug-naive animal under the same training conditions. Thus, the data from the present study confirmed the notion that low doses of PTZ and VPA in the naive animal may activate processes activated by drug withdrawal, including those important for the motivational effect of withdrawal. However, it was also pointed out that the lowest dose VPA producing aversion was higher than that found here to produce writhes and ataxia (80 mg/kg) but the same as that required for shaking (160 mg/kg), while the PTZ aversion was at a dose lower than that known to produce a PTZ cue. Implications were discussed for using withdrawal-like phenomena as a model in the non-treated organism of clinically-relevant withdrawal effects. PMID:7587968

  4. Signs and Symptoms

    MedlinePlus

    ... print email share facebook twitter google plus linkedin Signs and Symptoms Partly because there are different types ... This section presents a general picture of CMT signs and symptoms. Contractures and bone deformities Many people ...

  5. Dermatomyositis: Signs and Symptoms

    MedlinePlus

    ... print email share facebook twitter google plus linkedin Signs and Symptoms What happens to someone with dermatomyositis? ... be damaged as a result. About Dermatomyositis (DM) Signs and Symptoms Diagnosis Causes/Inheritance Medical Management Research ...

  6. Sign, Symbol and Form.

    ERIC Educational Resources Information Center

    Ballinger, Louise Bowen; Ballinger, Raymond A.

    Signs are such a commonplace sight in our everyday lives, that we can easily miss the artistic beauty and graphic harmony of the symbols used. Thoughtfully well designed and planned signs communicate with a simplicity and directness that signmakers and designers have adhered to for ages. Even contemporary signs still reflect their timelessness…

  7. British Sign Name Customs

    ERIC Educational Resources Information Center

    Day, Linda; Sutton-Spence, Rachel

    2010-01-01

    Research presented here describes the sign names and the customs of name allocation within the British Deaf community. While some aspects of British Sign Language sign names and British Deaf naming customs differ from those in most Western societies, there are many similarities. There are also similarities with other societies outside the more…

  8. On the System of Person-Denoting Signs in Estonian Sign Language: Estonian Name Signs

    ERIC Educational Resources Information Center

    Paales, Liina

    2010-01-01

    This article discusses Estonian personal name signs. According to study there are four personal name sign categories in Estonian Sign Language: (1) arbitrary name signs; (2) descriptive name signs; (3) initialized-descriptive name signs; (4) loan/borrowed name signs. Mostly there are represented descriptive and borrowed personal name signs among…

  9. 40 CFR 74.18 - Withdrawal.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... opt-in source may request to withdraw from the Acid Rain Program by submitting an administrative... paragraph (f)(1) of this section. (b) Requesting withdrawal. To withdraw from the Acid Rain Program, the...-in source's prior violations. An opt-in source that withdraws from the Acid Rain Program shall...

  10. 5 CFR 1650.11 - Withdrawal elections.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 5 Administrative Personnel 3 2012-01-01 2012-01-01 false Withdrawal elections. 1650.11 Section 1650.11 Administrative Personnel FEDERAL RETIREMENT THRIFT INVESTMENT BOARD METHODS OF WITHDRAWING FUNDS FROM THE THRIFT SAVINGS PLAN Post-Employment Withdrawals § 1650.11 Withdrawal elections....

  11. 5 CFR 1650.11 - Withdrawal elections.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 5 Administrative Personnel 3 2011-01-01 2011-01-01 false Withdrawal elections. 1650.11 Section 1650.11 Administrative Personnel FEDERAL RETIREMENT THRIFT INVESTMENT BOARD METHODS OF WITHDRAWING FUNDS FROM THE THRIFT SAVINGS PLAN Post-Employment Withdrawals § 1650.11 Withdrawal elections....

  12. 5 CFR 1650.11 - Withdrawal elections.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 5 Administrative Personnel 3 2010-01-01 2010-01-01 false Withdrawal elections. 1650.11 Section 1650.11 Administrative Personnel FEDERAL RETIREMENT THRIFT INVESTMENT BOARD METHODS OF WITHDRAWING FUNDS FROM THE THRIFT SAVINGS PLAN Post-Employment Withdrawals § 1650.11 Withdrawal elections....

  13. 5 CFR 1650.11 - Withdrawal elections.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 5 Administrative Personnel 3 2013-01-01 2013-01-01 false Withdrawal elections. 1650.11 Section 1650.11 Administrative Personnel FEDERAL RETIREMENT THRIFT INVESTMENT BOARD METHODS OF WITHDRAWING FUNDS FROM THE THRIFT SAVINGS PLAN Post-Employment Withdrawals § 1650.11 Withdrawal elections....

  14. 40 CFR 74.18 - Withdrawal.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... opt-in source may request to withdraw from the Acid Rain Program by submitting an administrative... paragraph (f)(1) of this section. (b) Requesting withdrawal. To withdraw from the Acid Rain Program, the...-in source's prior violations. An opt-in source that withdraws from the Acid Rain Program shall...

  15. 40 CFR 74.18 - Withdrawal.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 16 2010-07-01 2010-07-01 false Withdrawal. 74.18 Section 74.18 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) SULFUR DIOXIDE OPT-INS Permitting Procedures § 74.18 Withdrawal. (a) Withdrawal through administrative amendment. An opt-in source may request to withdraw...

  16. 40 CFR 74.18 - Withdrawal.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... opt-in source may request to withdraw from the Acid Rain Program by submitting an administrative... paragraph (f)(1) of this section. (b) Requesting withdrawal. To withdraw from the Acid Rain Program, the...-in source's prior violations. An opt-in source that withdraws from the Acid Rain Program shall...

  17. 40 CFR 74.18 - Withdrawal.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... opt-in source may request to withdraw from the Acid Rain Program by submitting an administrative... paragraph (f)(1) of this section. (b) Requesting withdrawal. To withdraw from the Acid Rain Program, the...-in source's prior violations. An opt-in source that withdraws from the Acid Rain Program shall...

  18. Differential effects of endocannabinoid catabolic inhibitors on morphine withdrawal in mice

    PubMed Central

    Gamage, Thomas F.; Ignatowska-Jankowska, Bogna M.; Muldoon, Pretal P.; Cravatt, Benjamin F.; Damaj, M. Imad; Lichtman, Aron H.

    2014-01-01

    Background Inhibition of endocannabinoid catabolic enzymes fatty acid amide hydrolase (FAAH) and/or monoacylglycerol lipase (MAGL) reduces somatic morphine withdrawal signs, but its effects on aversive aspects of withdrawal are unknown. The present study investigated whether Δ9-tetrahydrocannabinol (THC), the MAGL inhibitor JZL184, the FAAH inhibitor PF-3845, or the dual FAAH/MAGL inhibitor SA-57 would reduce acquisition of morphine withdrawal-induced conditioned place avoidance (CPA) and jumping. Methods Mice were implanted with placebo or 75 mg morphine pellets, 48 h later injected with naloxone or saline and placed in the conditioning apparatus, and assessed for CPA at 72 h. Subjects were also observed for jumping behavior following naloxone challenge. Results Naloxone (0.056 mg/kg) produced robust CPA in morphine-pelleted, but not placebo-pelleted, mice. Morphine pretreatment prevented the occurrence of withdrawal CPA and withdrawal jumping, while clonidine (an α2 adrenergic receptor agonist) only blocked withdrawal CPA. THC, JZL184, and SA-57 significantly reduced the percentage of mice that jumped during the conditioning session, but did not affect acquisition of withdrawal CPA. PF-3845 did not reduce morphine withdrawal CPA or jumping. Finally, neither THC nor the endocannabinoid catabolic enzyme inhibitors in non-dependent mice elicited a conditioned place preference or aversion. Conclusions These findings suggest that inhibiting endocannabinoid catabolic enzymes reduces somatic morphine withdrawal signs, but not aversive aspects as inferred in the CPA paradigm. The observation that non-dependent mice administered inhibitors of endocannabinoid degradation did not display place preferences is consistent with the idea that that endocannabinoid catabolic enzymes might be targeted therapeutically, with reduced risk of abuse. PMID:25479915

  19. Withdrawal: Expanding a Key Addiction Construct.

    PubMed

    Piper, Megan E

    2015-12-01

    Withdrawal is an essential component of classical addiction theory; it is a vital manifestation of dependence and motivates relapse. However, the traditional conceptualization of withdrawal as a cohesive collection of symptoms that emerge during drug deprivation and decline with either the passage of time or reinstatement of drug use, may be inadequate to explain scientific findings or fit with modern theories of addiction. This article expands the current understanding of tobacco withdrawal by examining: (1) withdrawal variability; (2) underlying causes of withdrawal variability, including biological and person factors, environmental influences, and the influence of highly routinized behavioral patterns; (3) new withdrawal symptoms that allow for enhanced characterization of the withdrawal experience; and (4) withdrawal-related cognitive processes. These topics provide guidance regarding the optimal assessment of withdrawal and illustrate the potential impact modern withdrawal conceptualization and assessment could have on identifying treatment targets. PMID:25744958

  20. Restlessness related to SSRI withdrawal.

    PubMed

    Hirose, S

    2001-02-01

    There are reports that abrupt withdrawal of various selective serotonin re-uptake inhibitors, such as fluvoxamine, can elicit in patients various withdrawal symptoms. Fluvoxamine has been widely used in Japan for approximately 1 year. However, there have been no case reports of withdrawal symptoms following abrupt fluvoxamine discontinuation in Japan. The author reports a case where the abrupt discontinuation of fluvoxamine produced restlessness in a depressed patient. The restlessness disappeared soon after the reinstatement of treatment with fluvoxamine. This case report suggests that clinicians should carefully scrutinize a patient's compliance to fluvoxamine as the withdrawal symptoms observed following abrupt discontinuation might be regarded as a relapse of depression or side-effects of the medicine. PMID:11235863

  1. Water withdrawals in Florida, 2012

    USGS Publications Warehouse

    Marella, Richard L.

    2015-01-01

    The largest percentage of freshwater withdrawals was from the South Florida Water Management District (46 percent), followed by the St. Johns River Water Management District (20 percent), Southwest Florida Water Management District (19 percent), Northwest Florida Water Management District (9 percent), and Suwannee River Water Management District (6 percent). The South Florida Water Management District accounted for the largest percentage of freshwater withdrawals for public-supply use (46 percent), commercial-industrial-mining self-supplied use (24 percent), agricultural self-supplied use (59 percent), and recreational-landscape irrigation use (63 percent). The Northwest Florida Water Management District accounted for the largest percentage of freshwater withdrawals for power-generation use (44 percent), and the Southwest Florida Water Management District accounted for the largest percentage of saline-water withdrawals for power-generation use (58 percent).

  2. Factor Analytical Investigation of Krathom (Mitragyna speciosa Korth.) Withdrawal Syndrome in Thailand.

    PubMed

    Saingam, Darika; Assanangkornchai, Sawitri; Geater, Alan F; Lerkiatbundit, Sanguan

    2016-01-01

    Krathom (Mitragyna speciosa Korth.) is an addictive and illicit substance used in Thailand and other Southeast Asian countries. It has become the most commonly used substance among villagers. The study aimed to explore the factor structure of the krathom withdrawal syndrome based on the findings of an earlier qualitative study. The current study was divided into two stages. Cross-sectional data collections were employed in both phases. The samples comprised, respectively, 196 and 330 krathom users aged over 25 years. The characteristics of krathom withdrawal symptoms and signs were identified and the factor structure examined using exploratory factor analysis (EFA). Confirmatory Factor Analysis (CFA) was used to examine the construct validity and multivariate linear regression was used to identify factors predicting the intensity of krathom withdrawal symptoms. The final scale comprised 20 items with four factors: craving-fatigue syndrome; musculoskeletal system and insomnia; mood symptoms; and autonomic nervous system/physical sickness. Symptoms and signs of krathom withdrawal similar to those of the withdrawal syndrome of opioid substances appear to be present in regular krathom users. The krathom withdrawal intensity is predicted by duration of krathom use, frequency, and daily amount of krathom use. PMID:27015537

  3. Who withdraws? Psychological individual differences and employee withdrawal behaviors.

    PubMed

    Zimmerman, Ryan D; Swider, Brian W; Woo, Sang Eun; Allen, David G

    2016-04-01

    Psychological individual differences, such as personality, affectivity, and general mental ability, have been shown to predict numerous work-related behaviors. Although there is substantial research demonstrating relationships between psychological individual differences and withdrawal behaviors (i.e., lateness, absenteeism, and turnover), there is no integrative framework providing scholars and practitioners a guide for conceptualizing how, why, and under what circumstances we observe such relationships. In this integrative conceptual review we: (a) utilize the Cognitive-Affective Processing System framework (Mischel & Shoda, 1995) to provide an overarching theoretical basis for how psychological individual differences affect withdrawal behaviors; (b) create a theoretical model of the situated person that summarizes the existing empirical literature examining the effect of psychological differences on withdrawal behavior; and (c) identify future research opportunities based on our review and integrative framework. (PsycINFO Database Record PMID:26595754

  4. Standardization of Sign Languages

    ERIC Educational Resources Information Center

    Adam, Robert

    2015-01-01

    Over the years attempts have been made to standardize sign languages. This form of language planning has been tackled by a variety of agents, most notably teachers of Deaf students, social workers, government agencies, and occasionally groups of Deaf people themselves. Their efforts have most often involved the development of sign language books…

  5. Sign-a-Palooza

    ERIC Educational Resources Information Center

    McMorran, Charles; Reynolds, Veronica

    2010-01-01

    A halo of signs, some stuffed into thick plastic sheaths while others curled under yellow tape, cluttered the service desks of the New City Library. They bleated out messages of closings, procedures, and warnings. Their number undermined their cause. All too often a customer would ask a question that was answered by the very sign they had pushed…

  6. The effects of chronic versus acute desipramine on nicotine withdrawal and nicotine self-administration in the rat

    PubMed Central

    Paterson, Neil E.; Semenova, Svetlana; Markou, Athina

    2008-01-01

    Rationale Nicotine withdrawal is characterized by depression-like symptomatology that may be mediated by dysregulations in norepinephrine transmission. These aversive aspects of nicotine withdrawal and the rewarding effects of nicotine play major roles in maintaining nicotine dependence. Objectives To evaluate the effects of desipramine (DMI), a preferential norepinephrine reuptake inhibitor and antidepressant, on preclinical models of nicotine dependence in rats. Methods A rate-independent current-intensity discrete-trial threshold intracranial self-stimulation procedure was used to assess brain reward function during nicotine withdrawal induced by cessation of nicotine infusion via subcutaneous osmotic minipumps (3.16 mg/kg/day, base). Nicotine withdrawal was also measured by somatic signs of withdrawal. DMI was administered acutely (2 or 5 mg/kg, salt) during nicotine/saline withdrawal. In other naïve rats, chronic DMI treatment via minipump (15 mg/kg/day, salt) began after 7 days of nicotine/saline exposure and continued during administration of nicotine/saline for 14 days and during nicotine/saline withdrawal. Additional rats acquired intravenous nicotine- or food-maintained responding, were prepared with DMI/vehicle-containing minipumps, and self-administered nicotine or food during 12 days of DMI/vehicle exposure. Results Acute DMI administration had no effect on threshold elevations observed in nicotine-withdrawing rats. Chronic DMI administration prevented the reward threshold elevations and the increased somatic signs of nicotine withdrawal. Although chronic DMI significantly decreased nicotine self-administration, it also decreased food-maintained responding. Conclusions The results suggest that norepinephrine reuptake inhibitors may be effective anti-smoking treatments that reduce the anhedonic depression-like and somatic components of nicotine withdrawal, and may alter the rewarding effects of nicotine and food. PMID:18438738

  7. Behavioral expression of opiate withdrawal is altered after prefrontocortical dopamine depletion in rats: monoaminergic correlates.

    PubMed

    Espejo, E F; Serrano, M I; Caillé, S; Stinus, L

    2001-08-01

    The objective of this study was to establish the effects of prefrontocortical dopamine depletion on opiate withdrawal and prefrontocortical neurochemical changes elicited by morphine dependence and withdrawal. The dopaminergic content was also measured in the nucleus accumbens during withdrawal, in order to detect reactive changes induced by prefrontocortical lesion. Withdrawal was induced by naloxone in morphine-dependent rats. Monoamine levels were analyzed post-mortem by high performance liquid cromatography. The results showed that chronic morphine dependence did not modify basal levels of monoamines in sham rats, revealing neuroadaptation of prefrontocortical dopamine, noradrenaline and serotonin systems to chronic morphine. The neuroadaptive phenomenon remained after prefrontocortical lesion (> 79% dopamine depletion). On the other hand, a strong increase of dopamine, noradrenaline, and serotonin contents in the medial prefrontal cortex of sham rats was detected during opiate withdrawal. However, in lesioned rats, the increase of prefrontocortical dopamine and serotonin content, but not that of noradrenaline, was much lower. In the nucleus accumbens, prefrontocortical lesion reactively enhanced the dopaminergic tone and, although opiate withdrawal reduced dopaminergic activity in both sham and lesioned rats, this reduction was less intense in the latter group. At a behavioral level, some symptoms of physical opiate withdrawal were exacerbated in lesioned rats (writhing, mastication, teeth-chattering, global score) and exploration was reduced. The findings hence indicate that: (i) prefrontocortical monoaminergic changes play a role in the behavioral expression of opiate withdrawal; (ii) the severity of some withdrawal signs are related to the dopaminergic and serotonergic tone of the medial prefrontal cortex rather than to the noradrenergic one, and (iii) an inverse relationship between mesocortical and mesolimbic dopaminergic systems exists. PMID:11425504

  8. 29 CFR 4219.18 - Withdrawal in a plan year in which substantially all employers withdraw.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 29 Labor 9 2010-07-01 2010-07-01 false Withdrawal in a plan year in which substantially all employers withdraw. 4219.18 Section 4219.18 Labor Regulations Relating to Labor (Continued) PENSION BENEFIT GUARANTY CORPORATION WITHDRAWAL LIABILITY FOR MULTIEMPLOYER PLANS NOTICE, COLLECTION, AND REDETERMINATION OF WITHDRAWAL LIABILITY Redetermination...

  9. Modified 'Joyce model' of opioid dependence/withdrawal.

    PubMed

    Raffa, Robert B; Tallarida, Ronald J

    2006-12-01

    By comprehensive and detailed measurement of the time course of withdrawal signs in rats, Joyce et al. (J. Theo. Biol. 240:531-537, 2006) recently provided a creative quantitative model of the onset of drug dependence based on the requirement of protein synthesis. Because the initial model fit the data imperfectly over the full time course, those authors postulated that additional features would be needed. We report excellent fit of the data (R(2)=0.96) by adding: (1) a transient early phase, and (2) a delay in the buildup of protein. PMID:17045985

  10. A Detection Model of College Withdrawal

    ERIC Educational Resources Information Center

    Pleskac, Timothy J.; Keeney, Jessica; Merritt, Stephanie M.; Schmitt, Neal; Oswald, Frederick L.

    2011-01-01

    Many students during their college careers consider withdrawing from their respective college or university. Understanding why some students decide to withdraw yet others persist has implications for both the well being of students as well as for institutes of higher education. The present study develops a model of the decision to withdraw drawing…

  11. 5 CFR 1604.7 - Withdrawals.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... Withdrawals. A service member may withdraw all or a portion of his or her account under the rules in 5 CFR... exception to them) are explained at 5 CFR part 1650. (c) Combat zone contributions. If a service member account contains combat zone contributions, the withdrawal will be distributed pro rata from all...

  12. Signs of Overload

    MedlinePlus

    ... Listen Text Size Email Print Share Signs of Overload Page Content Article Body Although stress is a ... 12 (Copyright © 2004 American Academy of Pediatrics) The information contained on this Web site should not be ...

  13. Warning Signs of Bullying

    MedlinePlus

    ... to talk to kids about bullying. Respond to Bullying Learn how to respond to bullying . From stopping ... away . Back to top Signs a Child is Bullying Others Kids may be bullying others if they: ...

  14. Symptoms and Warning Signs

    MedlinePlus

    ... Signs Past Issues / Spring 2008 Table of Contents Anorexia Nervosa emaciation (extremely thin from lack of nutrition) relentless ... from diuretic abuse severe dehydration from purging Binge Eating Disorder frequently eating large amounts of food (binge-eating) ...

  15. The du Bois sign.

    PubMed

    Voelpel, James H; Muehlberger, Thomas

    2011-03-01

    According to the current literature, the term "du Bois sign" characterizes the condition of a shortened fifth finger as a symptom of congenital syphilis, Down syndrome, dyscrania, and encephalic malformation. Modern medical dictionaries and text books attribute the eponym to the French gynecologist Paul Dubois (1795-1871). Yet, a literature analysis revealed incorrect references to the person and unclear definitions of the term. Our findings showed that the origin of the term is based on observations made by the Swiss dermatologist Charles du Bois (1874-1947) in connection with congenital syphilis. In addition, a further eponymical fifth finger sign is closely associated with the du Bois sign. In conclusion, the du Bois sign has only limited diagnostic value and is frequently occurring in the normal healthy population. PMID:21263293

  16. Alcohol Withdrawal and Cerebellar Mitochondria.

    PubMed

    Jung, Marianna E

    2015-08-01

    Cerebellar disorders trigger the symptoms of movement problems, imbalance, incoordination, and frequent fall. Cerebellar disorders are shown in various CNS illnesses including a drinking disorder called alcoholism. Alcoholism is manifested as an inability to control drinking in spite of adverse consequences. Human and animal studies have shown that cerebellar symptoms persist even after complete abstinence from drinking. In particular, the abrupt termination (ethanol withdrawal) of long-term excessive ethanol consumption has shown to provoke a variety of neuronal and mitochondrial damage to the cerebellum. Upon ethanol withdrawal, excitatory neurotransmitter molecules such as glutamate are overly released in brain areas including cerebellum. This is particularly relevant to the cerebellar neuronal network as glutamate signals are projected to Purkinje neurons through granular cells that are the most populated neuronal type in CNS. This excitatory neuronal signal may be elevated by ethanol withdrawal stress, which promotes an increase in intracellular Ca(2+) level and a decrease in a Ca(2+)-binding protein, both of which result in the excessive entry of Ca(2+) to the mitochondria. Subsequently, mitochondria undergo a prolonged opening of mitochondrial permeability transition pore and the overproduction of harmful free radicals, impeding adenosine triphosphate (ATP)-generating function. This in turn provokes the leakage of mitochondrial molecule cytochrome c to the cytosol, which triggers a cascade of adverse cytosol reactions. Upstream to this pathway, cerebellum under the condition of ethanol withdrawal has shown aberrant gene modifications through altered DNA methylation, histone acetylation, or microRNA expression. Interplay between these events and molecules may result in functional damage to cerebellar mitochondria and consequent neuronal degeneration, thereby contributing to motoric deficit. Mitochondria-targeting research may help develop a powerful new

  17. Double-blind study of alprazolam, diazepam, clonidine, and placebo in the alcohol withdrawal syndrome: preliminary findings.

    PubMed

    Adinoff, B

    1994-08-01

    Both a reduction in the inhibitory effects of GABA (disinhibition) and activation of the sympathetic nervous system are manifested during the alcohol withdrawal syndrome. This study was designed to explore the relative efficacy of medications that differentially affects these two biological systems: the benzodiazepines, which attenuate GABAergic disinhibition, and the alpha 2-adrenergic receptor agonists, which decrease sympathetic activation. The benzodiazepine diazepam (n = 6), the alpha 2-receptor agonist clonidine (n = 7), the benzodiazepine alprazolam (this is also purported to have alpha 2-receptor agonist properties) (n = 6), and placebo (n = 6) were evaluated in their effectiveness in decreasing signs and symptoms of alcohol withdrawal. Drug-free, alcohol-dependent patients were administered 1 of the 4 medications in a double-blind design until symptoms of withdrawal, as measured by the Clinical Instrument Withdrawal Assessment for Alcohol-Revised, were successfully treated. Alprazolam was significantly more efficacious than both clonidine and placebo in decreasing withdrawal symptoms. Diazepam was more effective than clonidine and placebo on some measures of withdrawal. Clonidine decreased systolic blood pressure significantly more than the other two active drugs and placebo, but was no more effective than placebo in decreasing other symptoms of withdrawal. Alprazolam did not significantly decrease blood pressure compared with diazepam or placebo. Despite the small sample size, these preliminary findings suggest that the efficacy of alprazolam in the treatment of alcohol withdrawal is related to its effect at the benzodiazepine receptor and not its alpha 2-receptor agonist properties. PMID:7978098

  18. Activation of brain NOP receptors attenuates acute and protracted alcohol withdrawal symptoms in the rat

    PubMed Central

    Economidou, Daina; Cippitelli, Andrea; Stopponi, Serena; Braconi, Simone; Clementi, Stefano; Ubaldi, Massimo; Martin-Fardon, Rèmi; Weiss, Friedbert; Massi, Maurizio; Ciccocioppo, Roberto

    2010-01-01

    BACKGROUND Alcohol withdrawal, refers to a cluster of symptoms that may occur from suddenly ceasing the use of alcohol after chronic or prolonged ingestion. These symptoms make alcohol abstinence difficult and increase the risk of relapse in recovering alcoholics. In previous studies, we demonstrated that treatment with N/OFQ significantly reduces alcohol consumption and attenuates alcohol-seeking behaviour induced by environmental conditioning factors or by stress in rats. In the present study we evaluated whether activation of brain NOP receptors may also attenuate alcohol withdrawal signs in rats. METHODS For this purpose animals were subjected to a 6 day chronic alcohol intoxication (by intragastric administration) and at 8, 10 and 12 hours following cessation of alcohol exposure they were treated intracerebroventricularly (ICV) with N/OFQ (0.0, 1.0 and 3.0 μg/rat). Somatic withdrawal signs were scored after ICV treatment. In a subsequent experiment, to evaluate N/OFQ effects on alcohol withdrawal-induced anxiety another group of rats was subjected to ethanol intoxication and after one week was tested for anxiety behavior in the elevated plus maze (EPM). In the last experiment an additional group of rats was tested for anxiety elicited by acute ethanol intoxication (hangover anxiety). For this purpose, animals received an acute dose (3.0 g/kg) of 20% alcohol and 12-h later were tested in the EPM following ICV N/OFQ (0.0, 1.0 and 2.0μg/rat). RESULTS Results showed that N/OFQ significantly reduced the expression of somatic withdrawal signs and reversed anxiety-like behaviors associated with both chronic and acute alcohol intoxication. N/OFQ did not affect anxiety scores in nondependent animals. CONCLUSIONS The present findings suggest that the N/OFQ-NOP receptor system may represent a promising target for the development of new treatments to ameliorate alcohol withdrawal symptoms. PMID:21223310

  19. Estimated freshwater withdrawals in Texas, 1990

    USGS Publications Warehouse

    Lurry, Dee L.

    1994-01-01

    Freshwater withdrawals in Texas during 1990 were estimated as part of the U.S. Geological Survey's National Water Use Information Program. Estimates of freshwater withdrawals were made for five categories of use: irrigation, thermoelectric- power generation, water supply, industrial and mining, and domestic/commercial/livestock. Total freshwater withdrawals for the State were estimated to be 20,100 Mgal/d (million gallons per day). Ground water was estimated to account for 37 percent (7,390 Mgal/d), and surface water was estimated to account for 63 percent (12,700 Mgal/d) of total withdrawals. The largest withdrawals of freshwater were for irrigation purposes.

  20. [Psychiatric complications of alcoholism: alcohol withdrawal syndrome and other psychiatric disorders].

    PubMed

    Maciel, Cláudia; Kerr-Corrêa, Florence

    2004-05-01

    Alcohol withdrawal syndrome is an acute condition secondary to total or partial reduction of alcohol consumption, characterized by self limited signs and symptoms and different degrees of severity. It can be complicated by several clinical and/or other psychiatric related problems. The objective of this article is to review the most important psychiatric complications to alcohol withdrawal syndrome as well as other psychiatric disorders associated with alcohol dependence as Wernicke Korsakoff and Marchiava Bignami syndromes. We aim to promote early diagnosis and treatment of these conditions, minimizing morbidity and mortality associated with them. PMID:15729445

  1. Low dose naltrexone administration in morphine dependent rats attenuates withdrawal-induced norepinephrine efflux in forebrain

    PubMed Central

    Van Bockstaele, Elisabeth J.; Qian, Yaping; Sterling, Robert C.; Page, Michelle E.

    2009-01-01

    The administration of low dose opioid antagonists has been explored as a potential means of detoxification in opiate dependence. Previous results from our laboratory have shown that concurrent administration of low dose naltrexone in the drinking water of rats implanted with subcutaneous morphine pellets attenuates behavioral and biochemical signs of withdrawal in brainstem noradrenergic nuclei. Noradrenergic projections originating from the nucleus tractus solitarius (NTS) and the locus coeruleus (LC) have previously been shown to be important neural substrates involved in the somatic expression of opiate withdrawal. The hypothesis that low dose naltrexone treatment attenuates noradrenergic hyperactivity typically associated with opiate withdrawal was examined in the present study by assessing norepinephrine tissue content and norepinephrine efflux using in vivo microdialysis coupled to high performance liquid chromatography (HPLC) with electrochemical detection (ED). The frontal cortex (FC), amygdala, bed nucleus of the stria terminalis (BNST) and cerebellum were analyzed for tissue content of norepinephrine following withdrawal in morphine dependent rats. Naltrexone precipitated withdrawal elicited a significant decrease in tissue content of norepinephrine in the BNST and amygdala. This decrease was significantly attenuated in the BNST of rats that received low dose naltrexone pretreatment compared to controls. No significant difference was observed in the other brain regions examined. In a separate group of rats, norepinephrine efflux was assessed with in vivo microdialysis in the BNST or the FC of morphine dependent rats or placebo treated rats subjected to naltrexone-precipitated withdrawal that received either naltrexone in their drinking water (5 mg/L) or unadulterated water. Following baseline dialysate collection, withdrawal was precipitated by injection of naltrexone and sample collection continued for an additional four hours. At the end of the

  2. Computational triadic algebras of signs

    SciTech Connect

    Zadrozny, W.

    1996-12-31

    We present a finite model of Peirce`s ten classes of signs. We briefly describe Peirce`s taxonomy of signs; we prove that any finite collection of signs can be extended to a finite algebra of signs in which all interpretants are themselves being interpreted; and we argue that Peirce`s ten classes of signs can be defined using constraints on algebras of signs. The paper opens the possibility of defining multimodal cognitive agents using Peirce`s classes of signs, and is a first step towards building a computational logic of signs based on Peirce`s taxonomies.

  3. The Meaning of Signs:

    PubMed Central

    Stein, Claudia

    2006-01-01

    This article reconstructs the diagnostic act of the French pox in the French-disease hospital of sixteenth-century Augsburg. It focuses on how the participants in the clinical encounter imagined the configuration of the pox and its localization in the human body. Of central importance for answering this question is the early modern conception of physical signs. It has been argued that it was due to a specific understanding of bodily signs and their relationship to a disease and its causes, that disease definition and classification in the early modern period showed a high degree of flexibility and fluidity. This paper looks at how the sixteenth-century theoretical conception of physical signs not only shaped the diagnosis and treatment of the pox but also reflected the overall organization of institutions. PMID:17242549

  4. Gastrointestinal motor alterations induced by precipitated benzodiazepine withdrawal in rats.

    PubMed

    Martinez, J; Fargeas, M J; Bueno, L

    1992-03-01

    The effects of benzodiazepine withdrawal on intestinal motor activity and propulsion were investigated in two groups of diazepam-dependent rats (15 mg/kg/day for 8 days). Withdrawal was precipitated by injection of two benzodiazepine antagonists (Ro 15.1788 and PK 11.95) acting on central and peripheral-type receptors, respectively. Intestinal motor activity was assessed by implanting electrodes for long-term electromyographic recordings. Gastrointestinal transit was evaluated after gavage by a marker (51CrO4Na2) and radioactivity counting. Both RO 15.1788 (15 mg/kg) and PK 11.195 (5 mg/kg) triggered an abstinence syndrome with behavioral and autonomic signs. At the intestinal level, Ro 15.1788 induced a phase of strong irregular spiking activity (173 +/- 63 min) which remained located in the duodenum. In contrast, PK 11.195 induced a period of propagated myoelectric complexes characterized by phases II and III of high amplitude. The cecal frequency was doubled during the 1st hr after withdrawal induced by the two antagonists. Both Ro 15.1788 and PK 11.195 at this dosage had no effect per se on intestinal motility in vehicle-treated rats. In the second group of rats, gastric emptying was enhanced by 49.4 and 45.6% by Ro 15.1788 and PK 11.195, respectively. In contrast, PK 11.195 was able to accelerate the intestinal transit more than did Ro 15.1788 (geometric center, 5.9 +/- 0.43 and 5.3 +/- 0.49, respectively, vs. 4.1 +/- 0.31 in control rats). Our study shows that precipitated benzodiazepine withdrawal in diazepam-dependent rats induces alterations of the intestinal myoelectrical activity leading to an increase of the gastrointestinal transit. Central and peripheral-type receptors are involved in these effects. PMID:1312156

  5. Eponymous signs in dermatology

    PubMed Central

    Madke, Bhushan; Nayak, Chitra

    2012-01-01

    Clinical signs reflect the sheer and close observatory quality of an astute physician. Many new dermatological signs both in clinical and diagnostic aspects of various dermatoses are being reported and no single book on dermatology literature gives a comprehensive list of these “signs” and postgraduate students in dermatology finds it difficult to have access to the description, as most of these resident doctor do not have access to the said journal articles. “Signs” commonly found in dermatologic literature with a brief discussion and explanation is reviewed in this paper. PMID:23189246

  6. Signs in Speare's "The Sign of the Beaver."

    ERIC Educational Resources Information Center

    Moseley, Ann

    1995-01-01

    Describes the use of signs in Elizabeth George Speare's "The Sign of the Beaver," in which a settler youth and a young Indian learn to communicate by signs, and how the signs reveal much about each character's culture. Summarizes the plot elements of the book, including characters who are not as sympathetic to the Indian point of view. (PA)

  7. l-theanine attenuates abstinence signs in morphine-dependent rhesus monkeys and elicits anxiolytic-like activity in mice.

    PubMed

    Wise, Laura E; Premaratne, Ishani D; Gamage, Thomas F; Lichtman, Aron H; Hughes, Larry D; Harris, Louis S; Aceto, Mario D

    2012-12-01

    l-theanine, 2-amino-4-(ethylcarbamoyl) butyric acid, an amino acid found in green tea (Camellia sinensis), is sold in the United States as a dietary supplement to reduce stress and improve cognition and mood. The observations that l-theanine has been shown to inhibit caffeine's stimulatory effects and that caffeine produces precipitated withdrawal signs in opioid-addicted monkeys and some opioid withdrawal signs in some normal monkeys, suggest that l-theanine may suppress opioid withdrawal signs. Additionally, l-theanine produces anxiolytic effects in humans indicating that it has anti-anxiety properties. Thus, in these studies we determined whether l-theanine attenuates opioid-withdrawal signs in morphine-dependent rhesus monkeys, a model for spontaneous opioid withdrawal in human opioid addicts. We also evaluated whether l-theanine decreases anxiety-like behavior in mice, using the elevated plus maze and marble burying assays. l-theanine significantly attenuated designated opioid withdrawal signs, including fighting, rigid abdominal muscles, vocalizing on palpation of abdomen, pacing, retching, wet-dog shakes, and masturbation. It had a relatively quick onset of action that persisted for at least 2.5h. l-theanine also produced anxiolytic-like effects in the elevated plus maze and the marble burying assay in naïve mice at doses that did not significantly affect motor behavior. The results of these studies suggest that l-theanine may be useful in the pharmacotherapy of treating opioid withdrawal as well as anxiety-associated behaviors. PMID:22935630

  8. Suicide Warning Signs

    MedlinePlus

    ... health professional or by call- ing the National Suicide Prevention Lifeline at 1-800-273-TALK if you or someone you know exhibits any of the following signs: n Threatening to ... or writing about death, dying, or suicide when these actions are out of the ordinary ...

  9. Sign Language Web Pages

    ERIC Educational Resources Information Center

    Fels, Deborah I.; Richards, Jan; Hardman, Jim; Lee, Daniel G.

    2006-01-01

    The World Wide Web has changed the way people interact. It has also become an important equalizer of information access for many social sectors. However, for many people, including some sign language users, Web accessing can be difficult. For some, it not only presents another barrier to overcome but has left them without cultural equality. The…

  10. Signing in Science

    ERIC Educational Resources Information Center

    Ashby, Rachael

    2013-01-01

    This article describes British Sign Language (BSL) as a viable option for teaching science. BSL is used by a vast number of people in Britain but is seldom taught in schools or included informally alongside lessons. With its new addition of a large scientific glossary, invented to modernise the way science is taught to deaf children, BSL breaks…

  11. Derivative Sign Patterns

    ERIC Educational Resources Information Center

    Clark, Jeffrey

    2011-01-01

    Analysis of the patterns of signs of infinitely differentiable real functions shows that only four patterns are possible if the function is required to exhibit the pattern at all points in its domain and that domain is the set of all real numbers. On the other hand all patterns are possible if the domain is a bounded open interval.

  12. Sign-away Pressures

    ERIC Educational Resources Information Center

    Rosen, Catherine E.

    1976-01-01

    Why would mental health clients sign release-of-information forms unless they thought a refusal to do so would jeopardize their access to service? The author believes that the practice of not advising clients of their rights to privacy has ethical implications that can compromise the value of the treatment. (Author)

  13. Signs of Success.

    ERIC Educational Resources Information Center

    Styles-Lopez, Robin

    1998-01-01

    Explains how to make a well-designed signage package that is effective and enhances visitor first impressions of an institution. Examines questions to ask when planning traffic-pattern signage and the significance of the different hierarchy of signs; concludes with advice on signage design. (GR)

  14. 29 CFR 4219.12 - Employers liable upon mass withdrawal.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 29 Labor 9 2010-07-01 2010-07-01 false Employers liable upon mass withdrawal. 4219.12 Section 4219... Redetermination of Withdrawal Liability Upon Mass Withdrawal § 4219.12 Employers liable upon mass withdrawal. (a... experiences successive mass withdrawals, an employer that has been determined to be liable under this...

  15. 29 CFR 4219.12 - Employers liable upon mass withdrawal.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 29 Labor 9 2011-07-01 2011-07-01 false Employers liable upon mass withdrawal. 4219.12 Section 4219... Redetermination of Withdrawal Liability Upon Mass Withdrawal § 4219.12 Employers liable upon mass withdrawal. (a... experiences successive mass withdrawals, an employer that has been determined to be liable under this...

  16. 29 CFR 4219.12 - Employers liable upon mass withdrawal.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 29 Labor 9 2013-07-01 2013-07-01 false Employers liable upon mass withdrawal. 4219.12 Section 4219... Redetermination of Withdrawal Liability Upon Mass Withdrawal § 4219.12 Employers liable upon mass withdrawal. (a... experiences successive mass withdrawals, an employer that has been determined to be liable under this...

  17. 29 CFR 4219.12 - Employers liable upon mass withdrawal.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 29 Labor 9 2012-07-01 2012-07-01 false Employers liable upon mass withdrawal. 4219.12 Section 4219... Redetermination of Withdrawal Liability Upon Mass Withdrawal § 4219.12 Employers liable upon mass withdrawal. (a... experiences successive mass withdrawals, an employer that has been determined to be liable under this...

  18. 29 CFR 4219.12 - Employers liable upon mass withdrawal.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 29 Labor 9 2014-07-01 2014-07-01 false Employers liable upon mass withdrawal. 4219.12 Section 4219... Redetermination of Withdrawal Liability Upon Mass Withdrawal § 4219.12 Employers liable upon mass withdrawal. (a... experiences successive mass withdrawals, an employer that has been determined to be liable under this...

  19. Estimated freshwater withdrawals in Washington, 2010

    USGS Publications Warehouse

    Lane, Ron C.; Welch, Wendy B.

    2015-01-01

    The amount of public- and self-supplied water used for domestic, irrigation, livestock, aquaculture, industrial, mining, and thermoelectric power was estimated for state, county, and eastern and western regions of Washington during calendar year 2010. Withdrawals of freshwater for offstream uses were estimated to be about 4,885 million gallons per day. The total estimated freshwater withdrawals for 2010 was approximately 15 percent less than the 2005 estimate because of decreases in irrigation and thermoelectric power withdrawals.

  20. Wrong Signs in Regression Coefficients

    NASA Technical Reports Server (NTRS)

    McGee, Holly

    1999-01-01

    When using parametric cost estimation, it is important to note the possibility of the regression coefficients having the wrong sign. A wrong sign is defined as a sign on the regression coefficient opposite to the researcher's intuition and experience. Some possible causes for the wrong sign discussed in this paper are a small range of x's, leverage points, missing variables, multicollinearity, and computational error. Additionally, techniques for determining the cause of the wrong sign are given.

  1. N-acetylcysteine decreased nicotine reward-like properties and withdrawal in mice

    PubMed Central

    Bowers, M.S.; Jackson, A.; Maldoon, P.P.; Damaj, M. I.

    2016-01-01

    Rationale N-acetylcysteine can increase extrasynaptic glutamate and reduce nicotine self-administration in rats and smoking rates in humans. Objectives The aim of this study was to determine if N-acetylcysteine modulates the development of nicotine place conditioning and withdrawal in mice. Methods N-acetylcysteine was given to nicotine-treated male ICR mice. Experiment 1: reward-like behavior. N-acetylcysteine (0, 5, 15, 30, or 60 mg/kg, i.p.) was given 15 min before nicotine (0.5 mg/kg, s.c.) or saline (10 ml/kg, s.c.) in an unbiased conditioned place preference (CPP) paradigm. Conditioning for highly palatable food served as control. Experiment 2: spontaneous withdrawal. The effect of N-acetylcysteine (0, 15, 30, 120 mg/kg, i.p.) on anxiety-like behavior, somatic signs, and hyperalgesia were measured 18 - 24 hrs after continuous nicotine (24 mg/kg/day, 14 days). Experiment 3: Mecamylamine-precipitated, withdrawal-induced aversion. The effect of N-acetylcysteine (0, 15, 30, 120 mg/kg, i.p.) on mecamylamine (3.5 mg/kg, i.p.) precipitated withdrawal was determined after continuous nicotine (24 mg/kg, i.p., 28 days) using the conditioned place aversion (CPA) paradigm. Results Dose-related reductions in the development of nicotine CPP, somatic withdrawal signs, hyperalgesia, and CPA were observed after N-acetylcysteine pretreatment. No effect of N-acetylcysteine were found on palatable food CPP, anxiety-like behavior, or motoric capacity (crosses between plus maze arms). Finally, N-acetylcysteine did not affect any measure in saline-treated mice at doses effective in nicotine-treated mice. Conclusions These are the first data suggesting that N-acetylcysteine blocks specific mouse behaviors associated with nicotine reward and withdrawal, which adds to the growing appreciation that N-acetylcysteine may have high clinical utility in combating nicotine dependence. PMID:26676982

  2. Protracted ethanol withdrawal in rats: Tolerance to the anxiolytic effects of diazepam and pentobarbital but not phenobarbital

    SciTech Connect

    Lai, H.; Prather, P.L. )

    1990-02-26

    Anxiety is a common symptom during ethanol withdrawal contributing to its continuous abuse and alcoholism. Ethanol withdrawal in rats produces an interoceptive discriminative stimulus (IDS) similar to that produced by the anxiogenic drug pentylenetetrazol (PTZ). This stimulus peaks at 12 hours after last dose of ethanol and thereafter the IDS is detected for several days (protracted withdrawal) by sensitization to a probe drug. previously, the authors have shown that during the protracted withdrawal, the IDS is enhanced by GABA receptor antagonists suggesting alteration of brain GABA systems. This report provides further evidence that chronic ethanol alters GABAergic systems. Rats were trained to discriminate PTZ (20 mg/kg, ip) from saline. Diazepam, pentobarbital and phenobarbital blocked the PTZ-IDS dose dependently. Ethanol, 4.5% w/v, was then given in a nutritionally complete diet for a week. On termination of the ethanol diet, rats exhibited signs and symptoms of withdrawal which returned to baseline within 3 days. During the protracted withdrawal period, the authors then redetermined the blockade of the PTZ-IDS. Significant tolerance was observed to the effectiveness of diazepam and pentobarbital, but not to phenobarbital. Since diazepam and pentobarbital produce significantly more enhancement of GABAergic activity than does phenobarbital, these data further suggest alteration of brain GABAergic systems during protracted withdrawal from ethanol.

  3. Improving Nursing Knowledge of Alcohol Withdrawal

    PubMed Central

    Berl, Kimberly; Collins, Michelle L.; Melson, Jo; Mooney, Ruth; Muffley, Cheryl; Wright-Glover, Angela

    2015-01-01

    Christiana Care Health System implemented a Care Management Guideline for Alcohol Withdrawal Symptom Management, which provided direction for inpatient screening for alcohol withdrawal risk, assessment, and treatment. Nurses educated on its use expressed confusion with the use of the assessment tools, pharmacokinetics, and pathophysiology of alcohol withdrawal and delirium tremens. Reeducation was provided by nursing professional development specialists. Pre- and postsurveys revealed that nurses were more confident in caring for patients with alcohol withdrawal. (See CE Video, Supplemental Digital Content 1, http://links.lww.com/JNPD/A9) PMID:25816126

  4. Manual Signing in Adults with Intellectual Disability: Influence of Sign Characteristics on Functional Sign Vocabulary

    ERIC Educational Resources Information Center

    Meuris, Kristien; Maes, Bea; De Meyer, Anne-Marie; Zink, Inge

    2014-01-01

    Purpose: The purpose of this study was to investigate the influence of sign characteristics in a key word signing (KWS) system on the functional use of those signs by adults with intellectual disability (ID). Method: All 507 signs from a Flemish KWS system were characterized in terms of phonological, iconic, and referential characteristics.…

  5. Vital signs monitoring system

    NASA Technical Reports Server (NTRS)

    Steffen, Dale A. (Inventor); Sturm, Ronald E. (Inventor); Rinard, George A. (Inventor)

    1981-01-01

    A system is disclosed for monitoring vital physiological signs. Each of the system components utilizes a single hybrid circuit with each component having high accuracy without the necessity of repeated calibration. The system also has low power requirements, provides a digital display, and is of sufficiently small size to be incorporated into a hand-carried case for portable use. Components of the system may also provide independent outputs making the component useful, of itself, for monitoring one or more vital signs. The overall system preferably includes an ECG amplifier and cardiotachometer signal conditioner unit, an impedance pneumograph and respiration rate signal conditioner unit, a heart/breath rate processor unit, a temperature monitoring unit, a selector switch, a clock unit, and an LCD driver unit and associated LCDs, with the system being capable of being expanded as needed or desired, such as, for example, by addition of a systolic/diastolic blood pressure unit.

  6. Withdrawing benzodiazepines in primary care.

    PubMed

    Lader, Malcolm; Tylee, Andre; Donoghue, John

    2009-01-01

    assisting in the discontinuation of benzodiazepines but the available data are insufficient for recommendations to be made regarding its use. Antidepressants can help if the patient is depressed before withdrawal or develops a depressive syndrome during withdrawal. The clearest strategy was to taper the medication; abrupt cessation can only be justified if a very serious adverse effect supervenes during treatment. No clear evidence suggests the optimum rate of tapering, and schedules vary from 4 weeks to several years. Our recommendation is to aim for withdrawal in <6 months, otherwise the withdrawal process can become the morbid focus of the patient's existence. Substitution of diazepam for another benzodiazepine can be helpful, at least logistically, as diazepam is available in a liquid formulation.Psychological interventions range from simple support through counselling to expert cognitive-behavioural therapy (CBT). Group therapy may be helpful as it at least provides support from other patients. The value of counselling is not established and it can be quite time consuming. CBT needs to be administered by fully trained and experienced personnel but seems effective, particularly in obviating relapse.The outcome of successful withdrawal is gratifying, both in terms of improved functioning and abstinence from the benzodiazepine usage. Economic benefits also ensue.Some of the principles of withdrawing benzodiazepines are listed. Antidepressants may be helpful, as may some symptomatic remedies. Care must be taken not to substitute one drug dependence problem for the original one. PMID:19062773

  7. Characterization of a pentylenetetrazol-like interoceptive stimulus produced by ethanol withdrawal.

    PubMed

    Lal, H; Harris, C M; Benjamin, D; Springfield, A C; Bhadra, S; Emmett-Oglesby, M W

    1988-11-01

    Rats were trained with food reinforcement to discriminate the anxiogenic drug pentylenetetrazol (PTZ, 20 mg/kg) from saline in a two-lever-choice task. In Experiment 1, ethanol, 8.25% w/v was given by gavage (7/day) for 4 days, with doses titrated to maintain moderate intoxication. After termination of ethanol, the rats exhibited mild overt signs of withdrawal and, in discrimination tests with saline as the test substance, they selected the PTZ lever, an effect reversed by ethanol, 2 g/kg, and by diazepam, 5 mg/kg. In Experiment 2, rats drank a nutritionally complete liquid diet containing ethanol, 4.5% w/v, for 1 week. They became tolerant to the intoxicating effect of ethanol, and blood ethanol concentration mounted with continued dosing. On termination of chronic ethanol, rats selected the PTZ lever before the onset of overt physical signs of withdrawal, and both measures returned to base line within 3 days. In Experiment 3 the percentage of rats selecting the PTZ lever after termination of ethanol depended upon the dose (up to 12.5 g/kg) and duration (up to a ceiling effect by 3 days) of ethanol administered chronically. These results indicate that a PTZ-like stimulus produced interoceptively can be demonstrated in the rat as an objective measure of ethanol withdrawal. This paradigm may provide insight into the symptom of anxiety associated with ethanol withdrawal. PMID:3183950

  8. A Case Report of Clonazepam Dependence: Utilization of Therapeutic Drug Monitoring During Withdrawal Period.

    PubMed

    Kacirova, Ivana; Grundmann, Milan; Silhan, Petr; Brozmanova, Hana

    2016-03-01

    Clonazepam is long-acting benzodiazepine agonist used in short-acting benzodiazepine withdrawal; however, recent observations suggest the existence of its abuse. We demonstrate a 40-year-old man with a 20-year history of psychiatric care with recently benzodiazepine dependence (daily intake of ∼60 mg of clonazepam and 10 mg of alprazolam). High serum levels of both drugs were analyzed 3 weeks before admission to hospitalization (clonazepam 543.9 ng/mL, alprazolam 110 ng/mL) and at the time of admission (clonazepam 286.2 ng/mL, alprazolam 140 ng/mL) without any signs of benzodiazepine intoxication. Gradual withdrawal of clonazepam with monitoring of its serum levels and increase of gabapentin dose were used to minimize physical signs and symptoms of clonazepam withdrawal. Alprazolam was discontinued promptly. Clinical consequences of the treatment were controllable tension, intermittent headache, and rarely insomia. It is the first case report showing utilization of therapeutic drug monitoring during withdrawal period in the patient with extreme toleration to severe benzodiazepine dependence. PMID:26945373

  9. Planetary Vital Signs

    NASA Astrophysics Data System (ADS)

    Kennel, Charles; Briggs, Stephen; Victor, David

    2016-07-01

    The climate is beginning to behave in unusual ways. The global temperature reached unprecedented highs in 2015 and 2016, which led climatologists to predict an enormous El Nino that would cure California's record drought. It did not happen the way they expected. That tells us just how unreliable temperature has become as an indicator of important aspects of climate change. The world needs to go beyond global temperature to a set of planetary vital signs. Politicians should not over focus policy on one indicator. They need to look at the balance of evidence. A coalition of scientists and policy makers should start to develop vital signs at once, since they should be ready at the entry into force of the Paris Agreement in 2020. But vital signs are only the beginning. The world needs to learn how to use the vast knowledge we will be acquiring about climate change and its impacts. Is it not time to use all the tools at hand- observations from space and ground networks; demographic, economic and societal measures; big data statistical techniques; and numerical models-to inform politicians, managers, and the public of the evolving risks of climate change at global, regional, and local scales? Should we not think in advance of an always-on social and information network that provides decision-ready knowledge to those who hold the responsibility to act, wherever they are, at times of their choosing?

  10. Oxidative Stress During Alcohol Withdrawal and its Relationship with Withdrawal Severity

    PubMed Central

    Parthasarathy, Ramamourty; Kattimani, Shivanand; Sridhar, M. G.

    2015-01-01

    Background: Oxidative parameters are altered during alcohol withdrawal and are said to contribute towards withdrawal symptoms in alcoholic patients. Aims: To study levels of five selected oxidative parameters during alcohol withdrawal state and after treatment of the withdrawal state and to assess the association of the oxidative parameters with the severity of alcohol withdrawal. Materials and Methods: This was a case-control study done in a De-addiction clinic of a tertiary teaching centre, Southern India. 50 persons having alcohol withdrawal symptoms were included. The oxidative stress parameters malondialdehyde, protein carbonyl, glutathione peroxidase, superoxide dismutase and catalase were assessed in during the withdrawal phase and again after the withdrawal had subsided. The same oxidative stress parameters were measured in the control group. Statistical analysis: Statistical analysis was done using SPSS version 17.0. One way ANOVA and Pearson correlation test were used for finding the association between the oxidative stress parameters levels and the severity of alcohol withdrawal. Multiple linear regression analysis done to predict variables associated with level of oxidative parameters. Results: During alcohol withdrawal the pro-oxidant malondialdehyde was elevated compared to that in the control group. Among the antioxidant enzymes the superoxide dismutase was higher and catalase was lower than the control group levels. After remission of the alcohol withdrawal both malondialdehyde remained higher and superoxide dismutase lower than in the control group. The levels of oxidative stress parameters not correlated with the severity of alcohol withdrawal. Conclusions: oxidative stress parameters show changes during alcohol withdrawal and during the remission of withdrawal. However, levels of oxidative stress parameters not correlated with the severity of withdrawal. PMID:25969603

  11. Withdrawal

    MedlinePlus

    ... for Kids for Teens Teens Home Body Mind Sexual Health Food & Fitness Diseases & Conditions Infections Q&A School & Jobs Drugs & Alcohol Staying Safe Recipes En Español Making a Change – Your Personal Plan Hot Topics Meningitis Choosing Your Mood Prescription Drug Abuse Healthy School Lunch ...

  12. Acute withdrawal: diagnosis and treatment.

    PubMed

    Brust, John C M

    2014-01-01

    Symptoms of alcohol withdrawal range in severity from mild "hangover" to fatal delirium tremens (DTs). Tremor, hallucinosis, and seizures usually occur within 48 hours of abstinence. Seizures tend to be generalized without focality, occurring singly or in a brief cluster, but status epilepticus is not unusual. DTs usually appears after 48 hours of abstinence and consists of marked inattentiveness, agitation, hallucinations, fluctuating level of alertness, marked tremulousness, and sympathetic overactivity. The mainstay of treatment for alcohol withdrawal is benzodiazepine pharmacotherapy, which can be used to control mild early symptoms, to prevent progression to DTs, or to treat DTs itself. Alternative less evidence-based pharmacotherapies include phenobarbital, anticonvulsants, baclofen, gamma-hydroxybutyric acid, beta-blockers, alpha-2-agonists, and N-methyl-d-aspartate receptor blockers. Treatment of DTs is a medical emergency requiring heavy sedation in an intensive care unit, with close attention to autonomic instability, fever, fluid loss, and electrolyte imbalance. Frequent comorbid disorders include hypoglycemia, liver failure, pancreatitis, sepsis, meningitis, intracranial hemorrhage, and Wernicke-Korsakoff syndrome. PMID:25307572

  13. Sign Lowering and Phonetic Reduction in American Sign Language

    PubMed Central

    Tyrone, Martha E.; Mauk, Claude E.

    2010-01-01

    This study examines sign lowering as a form of phonetic reduction in American Sign Language. Phonetic reduction occurs in the course of normal language production, when instead of producing a carefully articulated form of a word, the language user produces a less clearly articulated form. When signs are produced in context by native signers, they often differ from the citation forms of signs. In some cases, phonetic reduction is manifested as a sign being produced at a lower location than in the citation form. Sign lowering has been documented previously, but this is the first study to examine it in phonetic detail. The data presented here are tokens of the sign WONDER, as produced by six native signers, in two phonetic contexts and at three signing rates, which were captured by optoelectronic motion capture. The results indicate that sign lowering occurred for all signers, according to the factors we manipulated. Sign production was affected by several phonetic factors that also influence speech production, namely, production rate, phonetic context, and position within an utterance. In addition, we have discovered interesting variations in sign production, which could underlie distinctions in signing style, analogous to accent or voice quality in speech. PMID:20607146

  14. Planning Sign Languages: Promoting Hearing Hegemony? Conceptualizing Sign Language Standardization

    ERIC Educational Resources Information Center

    Eichmann, Hanna

    2009-01-01

    In light of the absence of a codified standard variety in British Sign Language and German Sign Language ("Deutsche Gebardensprache") there have been repeated calls for the standardization of both languages primarily from outside the Deaf community. The paper is based on a recent grounded theory study which explored perspectives on sign language…

  15. Sign Language Comprehension: The Case of Spanish Sign Language

    ERIC Educational Resources Information Center

    Rodriguez Ortiz, I. R.

    2008-01-01

    This study aims to answer the question, how much of Spanish Sign Language interpreting deaf individuals really understand. Study sampling included 36 deaf people (deafness ranging from severe to profound; variety depending on the age at which they learned sign language) and 36 hearing people who had good knowledge of sign language (most were…

  16. 46 CFR 391.5 - Qualified withdrawals.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 8 2011-10-01 2011-10-01 false Qualified withdrawals. 391.5 Section 391.5 Shipping MARITIME ADMINISTRATION, DEPARTMENT OF TRANSPORTATION REGULATIONS UNDER PUBLIC LAW 91-469 FEDERAL INCOME TAX ASPECTS OF THE CAPITAL CONSTRUCTION FUND § 391.5 Qualified withdrawals. (a) In general. (1)...

  17. 46 CFR 391.5 - Qualified withdrawals.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 8 2013-10-01 2013-10-01 false Qualified withdrawals. 391.5 Section 391.5 Shipping MARITIME ADMINISTRATION, DEPARTMENT OF TRANSPORTATION REGULATIONS UNDER PUBLIC LAW 91-469 FEDERAL INCOME TAX ASPECTS OF THE CAPITAL CONSTRUCTION FUND § 391.5 Qualified withdrawals. (a) In general. (1)...

  18. 46 CFR 391.5 - Qualified withdrawals.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 8 2014-10-01 2014-10-01 false Qualified withdrawals. 391.5 Section 391.5 Shipping MARITIME ADMINISTRATION, DEPARTMENT OF TRANSPORTATION REGULATIONS UNDER PUBLIC LAW 91-469 FEDERAL INCOME TAX ASPECTS OF THE CAPITAL CONSTRUCTION FUND § 391.5 Qualified withdrawals. (a) In general. (1)...

  19. 46 CFR 391.5 - Qualified withdrawals.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 8 2010-10-01 2010-10-01 false Qualified withdrawals. 391.5 Section 391.5 Shipping MARITIME ADMINISTRATION, DEPARTMENT OF TRANSPORTATION REGULATIONS UNDER PUBLIC LAW 91-469 FEDERAL INCOME TAX ASPECTS OF THE CAPITAL CONSTRUCTION FUND § 391.5 Qualified withdrawals. (a) In general. (1)...

  20. 42 CFR 457.170 - Withdrawal process.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 4 2011-10-01 2011-10-01 false Withdrawal process. 457.170 Section 457.170 Public... Plans for Child Health Insurance Programs and Outreach Strategies § 457.170 Withdrawal process. (a... amendment, or any portion of a proposed State plan or plan amendment, at any time during the review...

  1. 42 CFR 457.170 - Withdrawal process.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 4 2010-10-01 2010-10-01 false Withdrawal process. 457.170 Section 457.170 Public... Plans for Child Health Insurance Programs and Outreach Strategies § 457.170 Withdrawal process. (a... amendment, or any portion of a proposed State plan or plan amendment, at any time during the review...

  2. 14 CFR 93.223 - Slot withdrawal.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... AND GENERAL OPERATING RULES SPECIAL AIR TRAFFIC RULES Allocation of Commuter and Air Carrier IFR... essential air service operations or eliminating slots. Before withdrawing any slots under this section to... service operations shall be exempt from withdrawal for use for other international or essential...

  3. 14 CFR 93.223 - Slot withdrawal.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... AND GENERAL OPERATING RULES SPECIAL AIR TRAFFIC RULES Allocation of Commuter and Air Carrier IFR... essential air service operations or eliminating slots. Before withdrawing any slots under this section to... service operations shall be exempt from withdrawal for use for other international or essential...

  4. 27 CFR 28.153 - Withdrawal procedure.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ....153 Section 28.153 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY LIQUORS EXPORTATION OF ALCOHOL Withdrawal of Specially Denatured Spirits, Free of Tax, for Exportation or Transfer to a Foreign-Trade Zone § 28.153 Withdrawal procedure. The...

  5. 27 CFR 28.153 - Withdrawal procedure.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ....153 Section 28.153 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY LIQUORS EXPORTATION OF ALCOHOL Withdrawal of Specially Denatured Spirits, Free of Tax, for Exportation or Transfer to a Foreign-Trade Zone § 28.153 Withdrawal procedure. The...

  6. 27 CFR 28.153 - Withdrawal procedure.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ....153 Section 28.153 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY LIQUORS EXPORTATION OF ALCOHOL Withdrawal of Specially Denatured Spirits, Free of Tax, for Exportation or Transfer to a Foreign-Trade Zone § 28.153 Withdrawal procedure. The...

  7. 27 CFR 28.153 - Withdrawal procedure.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ....153 Section 28.153 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY ALCOHOL EXPORTATION OF ALCOHOL Withdrawal of Specially Denatured Spirits, Free of Tax, for Exportation or Transfer to a Foreign-Trade Zone § 28.153 Withdrawal procedure. The...

  8. 27 CFR 28.153 - Withdrawal procedure.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ....153 Section 28.153 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY ALCOHOL EXPORTATION OF ALCOHOL Withdrawal of Specially Denatured Spirits, Free of Tax, for Exportation or Transfer to a Foreign-Trade Zone § 28.153 Withdrawal procedure. The...

  9. 42 CFR 1008.40 - Withdrawal.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 42 Public Health 5 2013-10-01 2013-10-01 false Withdrawal. 1008.40 Section 1008.40 Public Health OFFICE OF INSPECTOR GENERAL-HEALTH CARE, DEPARTMENT OF HEALTH AND HUMAN SERVICES OIG AUTHORITIES ADVISORY OPINIONS BY THE OIG Submission of a Formal Request for an Advisory Opinion § 1008.40 Withdrawal....

  10. 42 CFR 1008.40 - Withdrawal.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... OPINIONS BY THE OIG Submission of a Formal Request for an Advisory Opinion § 1008.40 Withdrawal. The requestor of an advisory opinion may withdraw the request prior to the issuance of a formal advisory opinion... withdrawn, the requestor must pay the costs expended by the OIG in processing the opinion, as discussed...

  11. 42 CFR 1008.40 - Withdrawal.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... OPINIONS BY THE OIG Submission of a Formal Request for an Advisory Opinion § 1008.40 Withdrawal. The requestor of an advisory opinion may withdraw the request prior to the issuance of a formal advisory opinion... withdrawn, the requestor must pay the costs expended by the OIG in processing the opinion, as discussed...

  12. 42 CFR 1008.40 - Withdrawal.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... OPINIONS BY THE OIG Submission of a Formal Request for an Advisory Opinion § 1008.40 Withdrawal. The requestor of an advisory opinion may withdraw the request prior to the issuance of a formal advisory opinion... withdrawn, the requestor must pay the costs expended by the OIG in processing the opinion, as discussed...

  13. 42 CFR 1008.40 - Withdrawal.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... OPINIONS BY THE OIG Submission of a Formal Request for an Advisory Opinion § 1008.40 Withdrawal. The requestor of an advisory opinion may withdraw the request prior to the issuance of a formal advisory opinion... withdrawn, the requestor must pay the costs expended by the OIG in processing the opinion, as discussed...

  14. 49 CFR 365.123 - Applicant withdrawal.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 5 2013-10-01 2013-10-01 false Applicant withdrawal. 365.123 Section 365.123 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL MOTOR CARRIER SAFETY... APPLICATIONS FOR OPERATING AUTHORITY How To Apply for Operating Authority § 365.123 Applicant withdrawal....

  15. 49 CFR 107.111 - Withdrawal.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 2 2013-10-01 2013-10-01 false Withdrawal. 107.111 Section 107.111 Transportation Other Regulations Relating to Transportation PIPELINE AND HAZARDOUS MATERIALS SAFETY ADMINISTRATION... PROCEDURES Special Permits § 107.111 Withdrawal. An application may be withdrawn at any time before...

  16. 49 CFR 107.111 - Withdrawal.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 2 2010-10-01 2010-10-01 false Withdrawal. 107.111 Section 107.111 Transportation Other Regulations Relating to Transportation PIPELINE AND HAZARDOUS MATERIALS SAFETY ADMINISTRATION... PROCEDURES Special Permits § 107.111 Withdrawal. An application may be withdrawn at any time before...

  17. Measles (Rubeola): Signs and Symptoms

    MedlinePlus

    ... Initiative World Health Organization Pan American Health Organization Signs and Symptoms Language: English Español (Spanish) Recommend on ... of a patient with Koplik spots, an early sign of measles infection. Three to five days after ...

  18. CDC Vital Signs: Hispanic Health

    MedlinePlus

    ... Search The CDC Cancel Submit Search The CDC Vital Signs Note: Javascript is disabled or is not supported ... message, please visit this page: About CDC.gov . Vital Signs Current issue Infographic Topics Covered Alcohol Cancer Cardiovascular ...

  19. CDC Vital Signs: Legionnaires' Disease

    MedlinePlus

    ... Search The CDC Cancel Submit Search The CDC Vital Signs Note: Javascript is disabled or is not supported ... message, please visit this page: About CDC.gov . Vital Signs Current issue Infographic Topics Covered Alcohol Cancer Cardiovascular ...

  20. Aging changes in vital signs

    MedlinePlus

    ... Vital signs include body temperature, heart rate (pulse), breathing rate, and blood pressure. As you age, your vital ... symptoms and signs of infection. HEART RATE AND BREATHING RATE As you grow older, your pulse rate is ...

  1. CDC Vital Signs: Preventing Melanoma

    MedlinePlus

    ... Search The CDC Cancel Submit Search The CDC Vital Signs Note: Javascript is disabled or is not supported ... message, please visit this page: About CDC.gov . Vital Signs Current issue Infographic Topics Covered Alcohol Cancer Cardiovascular ...

  2. Signs of a Heart Attack

    MedlinePlus

    ... attack Heart Health and Stroke Signs of a heart attack Related information Make the Call. Don't Miss ... to top More information on Signs of a heart attack Read more from womenshealth.gov Make the Call, ...

  3. Kinship in Mongolian Sign Language

    ERIC Educational Resources Information Center

    Geer, Leah

    2011-01-01

    Information and research on Mongolian Sign Language is scant. To date, only one dictionary is available in the United States (Badnaa and Boll 1995), and even that dictionary presents only a subset of the signs employed in Mongolia. The present study describes the kinship system used in Mongolian Sign Language (MSL) based on data elicited from…

  4. Quine and the Segregrational Sign.

    ERIC Educational Resources Information Center

    Wolf, George

    1999-01-01

    In the context of theory of integrational linguistics, the segregational sign is distinguished from the integrational sign, and the operation of the former is analyzed. Focus is on how logic guides the sign, and how the theory of W. V. Quine accounts for these issues. (MSE)

  5. Sign language for telemanipulation

    NASA Astrophysics Data System (ADS)

    Pook, Polly K.; Ballard, Dana H.

    1995-12-01

    Literal teleoperation doesn't work very well. Limited bandwidth, long latencies, non- anthropomorphic mappings all make the effort of teleoperation tedious at best and ineffective at worst. Instead, users of teleoperated and semi-autonomous systems want their robots to `just do it for them,' without sacrificing the operator's intent. Our goal is to maximize human strategic control in teleoperator assisted robotics. In our teleassisted regime, the human operator provides high-level contexts for low-level autonomous robot behaviors. The operator wears an EXOS hand master to communicate via a natural sign language, such as pointing to objects and adopting a grasp preshape. Each sign indicates intention: e.g., reaching or grasping; and, where applicable, a spatial context: e.g., the pointing axis or preshape frame. The robot, a Utah/MIT hand on a Puma arm, acts under local servo control within the proscribed contexts. This paper extends earlier work [Pook & Ballard 1994a] by adding remote visual sensors to the teleassistance repertoire. To view the robot site, the operator wears a virtual research helmet that is coupled to binocular cameras mounted on a second Puma 760. The combined hand-head sensors allows teleassistance to be performed remotely. The example task is to open a door. We also demonstrate the flexibility of the teleassistance model by bootstrapping a `pick and place' task from the door opening task.

  6. INFINITY construction contract signed

    NASA Technical Reports Server (NTRS)

    2010-01-01

    Key state and community leaders celebrated April 6 with the signing of a construction contract for the state-of-the-art INFINITY Science Center planned near John C. Stennis Space Center in south Mississippi. Gulfport Mayor George Schloegel (l to r), chair of non-profit INFINITY Science Center Inc., was joined for the signing ceremony at the Hancock Bank in Gulfport by Virginia Wagner, sister of late Hancock Bank President Leo Seal Jr.; and Roy Anderson III, president and CEO of Roy Anderson Corp. Seal was the first chair of INFINITY Science Center Inc., which has led in development of the project. Roy Anderson Corp. plans to begin construction on the 72,000-square-foot, $28 million science and education center in May. The Mississippi Department of Transportation (MDOT) also is set to begin construction of a $2 million access road to the new center. The April 6 ceremony was attended by numerous officials, including former Stennis Space Center Directors Jerry Hlass and Roy Estess; Mississippi Senate President Pro Tempore Billy Hewes, R-Gulfport; Mississippi Rep. Diane Peranich, D-Pass Christian; and MDOT Southern District Commissioner Wayne Brown.

  7. Amphetamine withdrawal and sleep disturbance.

    PubMed

    Gossop, M R; Bradley, B P; Brewis, R K

    1982-01-01

    Sleep duration and indices of disturbed sleep, such as night-time waking and day-time sleep, were investigated in amphetamine users following hospital admission and withdrawal from the drug. Compared to controls, the amphetamine group showed an initial period of oversleeping and, towards the end of the first week, they showed a considerable degree of reduced sleep which persisted for the 20 days of this study. There was greater variability in sleep duration within the amphetamine group on almost all nights, and the variability in sleep duration from one night to the next was also greater. More night-time sleep disturbance was evident among the amphetamine ex-users. These results are discussed with respect to previous work and the pattern is seen to be more complex than had been imagined. A tentative neurochemical model is suggested and clinical implications are considered. PMID:7166130

  8. Arabic sign language: a perspective.

    PubMed

    Abdel-Fattah, M A

    2005-01-01

    Sign language in the Arab World has been recently recognized and documented. Many efforts have been made to establish the sign language used in individual countries, including Jordan, Egypt, Libya, and the Gulf States, by trying to standardize the language and spread it among members of the Deaf community and those concerned. Such efforts produced many sign languages, almost as many as Arabic-speaking countries, yet with the same sign alphabets. This article gives a tentative account of some sign languages in Arabic through reference to their possible evolution, which is believed to be affected by the diglossic situation in Arabic, and by comparing some aspects of certain sign languages (Jordanian, Palestinian, Egyptian, Kuwaiti, and Libyan) for which issues such as primes, configuration, and movement in addition to other linguistic features are discussed. A contrastive account that depicts the principal differences among Arabic sign languages in general and the spoken language is given. PMID:15778217

  9. Snamprogetti signs MTBE contracts

    SciTech Connect

    Alperowicz, N.

    1992-04-15

    Snamprogetti (Milan) will use a Russian-developed dehydrogenation process in a world-scale methyl tert-butyl ether (MTBE) plant it is to build at Arzew, Algeria for a previously announced joint venture of Sonatrach (Algiers), Total (Paris), and Ecofuel (Milan). The 600,000-m.t./year plant will be the first in the West to use the improved Snamprogetti-Yarsintez fluidized-bed dehydrogenation (FBD) technology proven on a demonstration plant at Yaroslavl, Russia. The process has also been selected for use in Oxyfuel Corp.`s 500,000-m.t./year MTBE plant near Beaumont, TX. Although the environmental permit is already in place, final agreement for this project has not yet been signed.

  10. Affective and somatic aspects of spontaneous and precipitated nicotine withdrawal in C57BL/6J and BALB/cByJ mice

    PubMed Central

    Stoker, Astrid K.; Semenova, Svetlana; Markou, Athina

    2008-01-01

    The aversive aspects of nicotine withdrawal are powerful motivational forces contributing to the tobacco smoking habit. We evaluated measures of affective and somatic aspects of nicotine withdrawal in C57BL/6J and BALB/cByJ mice. Nicotine withdrawal was induced by termination of chronic nicotine delivery through osmotic minipumps or precipitated with the nicotinic acetylcholine receptor (nAChR) antagonists mecamylamine or dihydro-β-erythroidine (DHβE). A rate-independent discrete-trial intracranial self-stimulation threshold procedure was used to assess brain reward function. Anxiety-like behavior and sensorimotor gating were assessed in the light-dark box and prepulse inhibition (PPI) tests, respectively. Acoustic startle response and somatic signs of withdrawal were also evaluated. Spontaneous nicotine withdrawal after 14-day exposure to 10–40 mg/kg/day nicotine induced no alterations in anxiety-like behavior, startle reactivity, PPI, or somatic signs in either strain, and no changes in thresholds in C57BL/6J mice. Extended 28-day exposure to 40 mg/kg/day nicotine induced threshold elevations, increased somatic signs, and anxiety-like behavior 24 h post-nicotine in C57BL/6J mice; thresholds returned to baseline levels by day 4 in nicotine-exposed mice. Mecamylamine or DHβE administration induced threshold elevations in nicotine-exposed C57BL/6J mice compared with saline-exposed mice. In conclusion, administration of relatively high nicotine doses over prolonged periods of time induces both the affective and somatic aspects of spontaneous nicotine withdrawal in the mouse, while exposure to nicotine for shorter periods of time is sufficient for nAChR antagonist-precipitated nicotine withdrawal. The current study is one of the first to demonstrate reward deficits associated with both spontaneous and nAChR antagonist-precipitated nicotine withdrawal in C57BL/6J mice. PMID:18452957

  11. Employing mirtazapine to aid benzodiazepine withdrawal.

    PubMed

    Chandrasekaran, P K

    2008-06-01

    Insomnia and depression are frequently encountered in patients during withdrawal from substances. While there are no approved medications for treating them, off-label attempts to address these phenomena with mirtazapine have shown some promising results. This case describes the use of mirtazapine as an aid in benzodiazepine withdrawal and its potential benefits in alleviating insomnia and depression in a 32-year-old man. It was found to ameliorate sleep myoclonus that was thought to be associated with his withdrawal syndrome. It is hoped this report will generate interest and stimulate further research in this area of psychopharmacology. PMID:18581012

  12. 12 CFR 925.26 - Voluntary withdrawal from membership.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 12 Banks and Banking 7 2010-01-01 2010-01-01 false Voluntary withdrawal from membership. 925.26... ASSOCIATES MEMBERS OF THE BANKS Withdrawal and Removal From Membership § 925.26 Voluntary withdrawal from membership. (a) In general. (1) Any institution may withdraw from membership by providing to the Bank...

  13. 19 CFR 144.31 - Right to withdraw.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... (CONTINUED) WAREHOUSE AND REWAREHOUSE ENTRIES AND WITHDRAWALS Withdrawals from Warehouse § 144.31 Right to withdraw. Withdrawals from bonded warehouse may be made only by the person primarily liable for the payment of duties on the merchandise being withdrawn, i.e., the importer of record on the warehouse...

  14. 19 CFR 144.27 - Withdrawal from warehouse by transferee.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 19 Customs Duties 2 2010-04-01 2010-04-01 false Withdrawal from warehouse by transferee. 144.27...; DEPARTMENT OF THE TREASURY (CONTINUED) WAREHOUSE AND REWAREHOUSE ENTRIES AND WITHDRAWALS Transfer of Right To Withdraw Merchandise from Warehouse § 144.27 Withdrawal from warehouse by transferee. At any time...

  15. SB242084, flumazenil, and CRA1000 block ethanol withdrawal-induced anxiety in rats.

    PubMed

    Knapp, Darin J; Overstreet, David H; Moy, Sheryl S; Breese, George R

    2004-02-01

    Anxiety-like behaviors are integral features of withdrawal from chronic ethanol exposure. In the experiments in the current study, we tested the hypothesis that anxiety can be regulated independently of other withdrawal signs and thus may be responsive to selective pharmacological agents. For 17 days, rats were fed ethanol (8-12 g/kg/day) in a liquid diet. Between 5 and 6 h after cessation of ethanol treatment, rats were tested in either the social interaction or plus-maze test of anxiety-like behavior after treatment with drugs hypothesized to have anxiolytic action. SB242084, flumazenil, and CRA1000-antagonists for 5-hydroxytryptamine (serotonin) (5-HT) 2C (5-HT(2C)), benzodiazepine, and corticotropin-releasing factor type 1 (CRF(1)) receptors, respectively-attenuated decreased social interaction without concomitant effects on activity measures. In contrast, ifenprodil, MDL 72222, and zolpidem-antagonists for N-methyl-d-aspartate (NMDA) and 5-HT(3) receptors, and agonist for benzodiazepine type 1 receptors, respectively-did not share this effect. Results for SB242084, flumazenil, and ifenprodil in the elevated plus-maze test were comparable to those in the social interaction test. These results support the suggestion that multiple neuronal systems (CRF(1), 5-HT(2C), and benzodiazepine receptors) contribute to the ethanol withdrawal sign of decreased social interaction. Furthermore, the selective effects of pharmacological agents on social interaction seem to indicate that this behavior can be dissociated from other signs. Because anxiety may be a complicating factor in alcohol withdrawal and relapse, future studies of this type are needed to provide focus for the effort to define selective and novel antianxiety agents for these disorders. PMID:15163561

  16. Vocalizations during withdrawal from opiates and cocaine: possible expressions of affective distress.

    PubMed

    Covington, Herbert E; Miczek, Klaus A

    2003-04-25

    Intense anxiety has been postulated to trigger relapse to abuse of opiates and psychomotor stimulants. Preclinical research methodologies need to be developed to adequately characterize the affective or emotional component of withdrawal. Classically, withdrawal from psychomotor stimulants and opiates focuses on somatic and autonomic indices, foremost based on observational assessments and, additionally, on measures of disrupted conditioned behavior. These measures depict the intensity and time course of withdrawal from specific doses of opiates and psychomotor stimulants, but require large numbers of subjects due to single use of each individual. Behavioral disruptions have been attributed to anhedonia, a core symptom of drug withdrawal, as well as major depressive and psychotic disorders. In spite of some pharmacological validation, inferences about anxiety-like disturbances, based on observed somatic and autonomic signs or on changes in conditioned responses, have to remain tentative. High-pitched vocalizations may communicate affective expressions and, in rodents, different kinds of ultrasonic vocalizations communicate maternal separation distress in infants, accompany the intensely arousing phases of agonistic confrontations, signal submission and distress in defensive responses to threats and painful events, and are part of the excitatory and inhibitory phases of sexual behavior. While acute treatment with opiates, psychomotor stimulants, alcohol and benzodiazepines suppresses ultrasonic vocalizations in the 22-25-kHz range, rats emit high rates of ultrasonic vocalizations upon withdrawal from prolonged exposure to these drugs, particularly if they have been startled. Peak rates of ultrasonic distress calls occur ca. 1-3 days after cessation of cocaine or opiate treatment and decline within 5-7 days. Ultrasonic vocalizations during withdrawal from cocaine, alcohol or benzodiazepines can be attenuated by renewed access to the drug. It will be informative to

  17. Estimated Freshwater Withdrawals in Oklahoma, 1990

    USGS Publications Warehouse

    Lurry, Dee L.; Tortorelli, Robert L.

    1996-01-01

    This report presents 1990 freshwater withdrawal estimates for Oklahoma by source and category. Withdrawal source is either ground water or surface water. Withdrawal categories include: irrigation, water supply, livestock, thermoelectric-power generation, domestic and commercial, and industrial and mining. Withdrawal data are aggregated by county, major aquifer, and principal river basin. Only the four major categories of irrigation, water supply, livestock, and thermoelectric-power generation are illustrated in this report, although data for all categories are tabulated. The U.S. Geological Survey (USGS) established the National Water-Use Information Program in 1977 to collect uniform, current, and reliable information on water use. The Oklahoma District of the USGS and the Oklahoma Water Resources Board participate in a cooperative program to collect and publish water-use information for Oklahoma. Data contained in this report were made available through the cooperative program.

  18. IDENTIFICATION AND MANAGEMENT OF ALCOHOL WITHDRAWAL SYNDROME

    PubMed Central

    Mirijello, Antonio; D’Angelo, Cristina; Ferrulli, Anna; Vassallo, Gabriele; Antonelli, Mariangela; Caputo, Fabio; Leggio, Lorenzo; Gasbarrini, Antonio; Addolorato, Giovanni

    2016-01-01

    Symptoms of alcohol withdrawal syndrome may develop within 6–24 hours after the abrupt discontinuation or decrease of alcohol consumption. Symptoms can vary from autonomic hyperactivity and agitation to delirium tremens. The gold-standard treatment for alcohol withdrawal syndrome is represented by benzodiazepines. Among them, different agents (i.e., long-acting or short-acting) and different regimens (front-loading, fixed dose or symptom-triggered) may be chosen on the basis of patient characteristics. Severe withdrawal could require ICU admission and the use of barbiturates or propofol. Other drugs, such as alpha2-agonists (clonidine and dexmetedomidine) and beta-blockers can be used as adjunctive treatments to control neuroautonomic hyperactivity. Furthermore, neuroleptics can help control hallucinations. Finally, other medications for the treatment for alcohol withdrawal syndrome have been investigated with promising results. These include carbamazepine, valproate, sodium oxybate, baclofen, gabapentin, and topiramate. The usefulness of these agents will be discussed in the text. PMID:25666543

  19. Anxiogenic effects of cocaine withdrawal in zebrafish.

    PubMed

    López-Patiño, Marcos A; Yu, Lili; Cabral, Howard; Zhdanova, Irina V

    2008-01-28

    Continued usage of cocaine is determined by genetic, conditioned and homeostatic factors, while it is reinforced by drug-induced reward and the emotionally negative state of drug withdrawal, which includes anxiety. The molecular mechanisms of these long-term behavioral and physiological alterations have yet to be fully elucidated. Here we demonstrate that in zebrafish, a wide range of non-anesthetic cocaine doses, 0.015-15 muM, does not result in acute alterations in locomotor activity, in spite of the high brain cocaine levels induced (7-120 pg/microg protein). Conversely, cocaine withdrawal causes hyperactivity associated with stereotypy. The behavioral hyperactivity is progressively increased during the initial period of withdrawal (24-72 h) and is maintained for at least 5 days. Such effect of cocaine withdrawal is aggravated by environmental stimulation and attenuated in the home environment. Administration of cocaine (1.5 microM) or a non-sedative dose of diazepam (5 microM, immersion) acutely counteracts withdrawal-associated hyperactivity and stereotypy in zebrafish, with the magnitude of these effects positively correlating with the degree of prior increase in basal activity. Administration of an anxiogenic benzodiazepine inverse agonist, FG-7142, results in zebrafish behavior similar to that observed during cocaine withdrawal. Together, the results suggest that cocaine withdrawal produces long-lasting behavioral effects in zebrafish which are consistent with an anxiety-like state. Thus, zebrafish, a powerful model for the study of vertebrate genetics, could provide insights into the molecular mechanisms of drug withdrawal. PMID:17889042

  20. Stop Sign Crater

    NASA Technical Reports Server (NTRS)

    2003-01-01

    [figure removed for brevity, see original site]

    With its rim eroded off by catastrophic floods in Tiu Vallis and its strangely angular shape, this 12 km diameter crater looks vaguely like a stop sign.

    Note: this THEMIS visual image has not been radiometrically nor geometrically calibrated for this preliminary release. An empirical correction has been performed to remove instrumental effects. A linear shift has been applied in the cross-track and down-track direction to approximate spacecraft and planetary motion. Fully calibrated and geometrically projected images will be released through the Planetary Data System in accordance with Project policies at a later time.

    NASA's Jet Propulsion Laboratory manages the 2001 Mars Odyssey mission for NASA's Office of Space Science, Washington, D.C. The Thermal Emission Imaging System (THEMIS) was developed by Arizona State University, Tempe, in collaboration with Raytheon Santa Barbara Remote Sensing. The THEMIS investigation is led by Dr. Philip Christensen at Arizona State University. Lockheed Martin Astronautics, Denver, is the prime contractor for the Odyssey project, and developed and built the orbiter. Mission operations are conducted jointly from Lockheed Martin and from JPL, a division of the California Institute of Technology in Pasadena.

    Image information: VIS instrument. Latitude 8.6, Longitude 329.2 East (30.8 West). 19 meter/pixel resolution.

  1. Withdrawing Benzodiazepines in Patients With Anxiety Disorders.

    PubMed

    Lader, Malcolm; Kyriacou, Andri

    2016-01-01

    The large class of CNS-depressant medications-the benzodiazepines-have been extensively used for over 50 years, anxiety disorders being one of the main indications. A substantial proportion (perhaps up to 20-30 %) of long-term users becomes physically dependent on them. Problems with their use became manifest, and dependence, withdrawal difficulties and abuse were documented by the 1980s. Many such users experience physical and psychological withdrawal symptoms on attempted cessation and may develop clinically troublesome syndromes even during slow tapering. Few studies have been conducted to establish the optimal withdrawal schedules. The usual management comprises slow withdrawal over weeks or months together with psychotherapy of various modalities. Pharmacological aids include antidepressants such as the SSRIs especially if depressive symptoms supervene. Other pharmacological agents such as the benzodiazepine antagonist, flumazenil, and the hormonal agent, melatonin, remain largely experimental. The purpose of this review is to analyse the evidence for the efficacy of the usual withdrawal regimes and the newer agents. It is concluded that little evidence exists outside the usual principles of drug withdrawal but there are some promising leads. PMID:26733324

  2. Alcohol Withdrawal Syndrome: Benzodiazepines and Beyond

    PubMed Central

    Sachdeva, Ankur; Chandra, Mina

    2015-01-01

    Alcohol dependence is an increasing and pervasive problem. Alcohol withdrawal symptoms are a part of alcohol dependence syndrome and are commonly encountered in general hospital settings, in most of the departments. Alcohol withdrawal syndrome ranges from mild to severe. The severe complicated alcohol withdrawal may present with hallucinations, seizures or delirium tremens. Benzodiazepines have the largest and the best evidence base in the treatment of alcohol withdrawal, and are considered the gold standard. Others, such as anticonvulsants, barbiturates, adrenergic drugs, and GABA agonists have been tried and have evidence. Supportive care and use of vitamins is essential in the management. Symptom triggered regime is favoured over fixed tapering dose regime, although monitoring through scales is cumbersome. This article aims to review the evidence base for appropriate clinical management of the alcohol withdrawal syndrome. We searched Pubmed for articles published in English on ‘Alcohol withdrawal syndrome’ in humans during the last 10 years. A total of 1182 articles came up. Articles not relevant to clinical utility and management were excluded based on the titles and abstract available. Full text articles, meta-analyses, systematic reviews and randomized controlled trials were obtained from this list and were considered for review. PMID:26500991

  3. Alcohol Withdrawal Syndrome: Benzodiazepines and Beyond.

    PubMed

    Sachdeva, Ankur; Choudhary, Mona; Chandra, Mina

    2015-09-01

    Alcohol dependence is an increasing and pervasive problem. Alcohol withdrawal symptoms are a part of alcohol dependence syndrome and are commonly encountered in general hospital settings, in most of the departments. Alcohol withdrawal syndrome ranges from mild to severe. The severe complicated alcohol withdrawal may present with hallucinations, seizures or delirium tremens. Benzodiazepines have the largest and the best evidence base in the treatment of alcohol withdrawal, and are considered the gold standard. Others, such as anticonvulsants, barbiturates, adrenergic drugs, and GABA agonists have been tried and have evidence. Supportive care and use of vitamins is essential in the management. Symptom triggered regime is favoured over fixed tapering dose regime, although monitoring through scales is cumbersome. This article aims to review the evidence base for appropriate clinical management of the alcohol withdrawal syndrome. We searched Pubmed for articles published in English on 'Alcohol withdrawal syndrome' in humans during the last 10 years. A total of 1182 articles came up. Articles not relevant to clinical utility and management were excluded based on the titles and abstract available. Full text articles, meta-analyses, systematic reviews and randomized controlled trials were obtained from this list and were considered for review. PMID:26500991

  4. Antiepileptic Drug Withdrawal in Dogs with Epilepsy

    PubMed Central

    Gesell, Felix Kaspar; Hoppe, Sonja; Löscher, Wolfgang; Tipold, Andrea

    2015-01-01

    Epilepsy is one of the most common neurological disorders in dogs and is treated by chronic administration of antiepileptic drugs (AEDs). In human beings with epilepsy, it is common clinical practice to consider drug withdrawal after a patient has been in remission (seizure free) for three or more years, but withdrawal is associated with the risk of relapse. In the present study, the consequences of AED withdrawal were studied in dogs with epilepsy. Therefore, 200 owners of dogs with idiopathic or presumed idiopathic epilepsy were contacted by telephone interview, 138 cases could be enrolled. In 11 cases, the therapy had been stopped after the dogs had become seizure free for a median time of 1 year. Reasons for AED withdrawal were appearance or fear of adverse side effects, financial aspects, and the idea that the medication could be unnecessary. Following AED withdrawal, four of these dogs remained seizure free, seven dogs suffered from seizure recurrence, of which only three dogs could regain seizure freedom after resuming AED therapy. Due to the restricted case number, an exact percentage of dogs with seizure recurrence after AED withdrawal cannot be given. However, the present study gives a hint that similar numbers as in human patients are found, and the data can help owners of epileptic dogs and the responsible clinician to decide when and why to stop antiepileptic medication. PMID:26664952

  5. Signs of Change: Contemporary Attitudes to Australian Sign Language

    ERIC Educational Resources Information Center

    Slegers, Claudia

    2010-01-01

    This study explores contemporary attitudes to Australian Sign Language (Auslan). Since at least the 1960s, sign languages have been accepted by linguists as natural languages with all of the key ingredients common to spoken languages. However, these visual-spatial languages have historically been subject to ignorance and myth in Australia and…

  6. 19 CFR 19.6 - Deposits, withdrawals, blanket permits to withdraw and sealing requirements.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... withdrawal permit has been issued. Duty-paid or unconditionally duty-free merchandise which has been... withdrawal for transportation to another port by a duty-free sales enterprise which meets the requirements...-free merchandise intended for passengers' on-board purchases when expressly authorized in writing...

  7. Kinematic Parameters of Signed Verbs

    ERIC Educational Resources Information Center

    Malaia, Evie; Wilbur, Ronnie B.; Milkovic, Marina

    2013-01-01

    Purpose: Sign language users recruit physical properties of visual motion to convey linguistic information. Research on American Sign Language (ASL) indicates that signers systematically use kinematic features (e.g., velocity, deceleration) of dominant hand motion for distinguishing specific semantic properties of verb classes in production…

  8. Sign Program for a University.

    ERIC Educational Resources Information Center

    Architectural and Engineering News, 1968

    1968-01-01

    A co-ordinated sign program for a multi-campus university not only helps students and visitors find their way around, but is a design element that adds identification and unity. Graphic designer, Paul Arthur, has designed a modular sign system for the University of Tennessee with all elements having standard color, lettering, size and materials.…

  9. Arabic Sign Language: A Perspective

    ERIC Educational Resources Information Center

    Abdel-Fattah, M. A.

    2005-01-01

    Sign language in the Arab World has been recently recognized and documented. Many efforts have been made to establish the sign language used in individual countries, including Jordan, Egypt, Libya, and the Gulf States, by trying to standardize the language and spread it among members of the Deaf community and those concerned. Such efforts produced…

  10. NUHOMS{reg_sign} update

    SciTech Connect

    Rich, N.

    1995-12-31

    NUHOMS{reg_sign} is the dry spent fuel storage and transportation technology selected to date by the majority of commercial nuclear utilities. The author first gives a system overview of the NUHOMS{reg_sign}. Next she discusses the project status and licensing status. She closes with an update of the multi-purpose canister.

  11. Symmetry in Sign Language Poetry

    ERIC Educational Resources Information Center

    Sutton-Spence, Rachel; Kaneko, Michiko

    2007-01-01

    This paper considers the range of ways that sign languages use geometric symmetry temporally and spatially to create poetic effect. Poets use this symmetry in sign language art to highlight duality and thematic contrast, and to create symbolic representations of beauty, order and harmony. (Contains 8 tables, 14 figures and 6 notes.)

  12. Keresan Pueblo Indian Sign Language.

    ERIC Educational Resources Information Center

    Kelley, Walter P.; McGregor, Tony L.

    This paper describes the use of Keresan Pueblo Indian Sign Language (KPISL) in one small, Keresan-speaking pueblo in central New Mexico, where 15 out of 650 tribal members have severe to profound hearing loss (twice the national average). KPISL did not originate for the same purposes as the Plains Indian Sign Language, (PISL) which was developed…

  13. Signing Apes and Evolving Linguistics.

    ERIC Educational Resources Information Center

    Stokoe, William C.

    Linguistics retains from its antecedents, philology and the study of sacred writings, some of their apologetic and theological bias. Thus it has not been able to face squarely the question how linguistic function may have evolved from animal communication. Chimpanzees' use of signs from American Sign Language forces re-examination of language…

  14. Inflated reward value in early opiate withdrawal.

    PubMed

    Wassum, Kate M; Greenfield, Venuz Y; Linker, Kay E; Maidment, Nigel T; Ostlund, Sean B

    2016-03-01

    Through incentive learning, the emotional experience of a reward in a relevant need state (e.g. hunger for food) sets the incentive value that guides the performance of actions that earn that reward when the need state is encountered again. Opiate withdrawal has been proposed as a need state in which, through experience, opiate value can be increased, resulting in escalated opiate self-administration. Endogenous opioid transmission plays anatomically dissociable roles in the positive emotional experience of reward consumption and incentive learning. We, therefore, sought to determine if chronic opiate exposure and withdrawal produces a disruption in the fundamental incentive learning process such that reward seeking, even for non-opiate rewards, can become maladaptive, inconsistent with the emotional experience of reward consumption and irrespective of need. Rats trained to earn sucrose or water on a reward-seeking chain were treated with morphine (10-30 mg/kg, s.c.) daily for 11 days prior to testing in withdrawal. Opiate-withdrawn rats showed elevated reward-seeking actions, but only after they experienced the reward in withdrawal, an effect that was strongest in early (1-3 days), as opposed to late (14-16 days), withdrawal. This was sufficient to overcome a negative reward value change induced by sucrose experience in satiety and, in certain circumstances, was inconsistent with the emotional experience of reward consumption. Lastly, we found that early opiate withdrawal-induced inflation of reward value was blocked by inactivation of basolateral amygdala mu opioid receptors. These data suggest that in early opiate withdrawal, the incentive learning process is disrupted, resulting in maladaptive reward seeking. PMID:25081350

  15. Carisoprodol: abuse potential and withdrawal syndrome.

    PubMed

    Reeves, Roy R; Burke, Randy S

    2010-03-01

    Carisoprodol (N-isopropyl-2 methyl-2-propyl-1,3-propanediol dicarbamate; N-isopropylmeprobamate) is a centrally acting skeletal muscle relaxant whose primary active metabolite is meprobamate, a substance with well established abuse potential similar to that of benzodiazepines. A number of reports show that carisoprodol has been abused for its sedative and relaxant effects, to augment or alter the effects of other drugs, and by the intentional combination of carisoprodol and other noncontrolled medications because of the relative ease (as compared to controlled substances) of obtaining prescriptions. The diversion and abuse of carisoprodol and its adverse health effects appear to have dramatically increased over the last several years. Clinicians have begun to see a withdrawal syndrome consisting of insomnia, vomiting, tremors, muscle twitching, anxiety, and ataxia in patients who abruptly cease intake of large doses of carisoprodol. Hallucinations and delusions may also occur. The withdrawal symptoms are very similar to those previously described for meprobamate withdrawal, suggesting that what may actually be occurring is withdrawal from meprobamate accumulated as a result of intake of excessive amounts of carisoprodol. However carisoprodol itself is capable of modulating GABA(A) function, and this may contribute both to the drugs abuse potential and to the occurrence of a withdrawal syndrome with abrupt cessation of intake. Carisoprodol has been classified as a controlled substance in several states in the US and restrictions on the use of the drug have been imposed in some European countries. Carisoprodol is metabolized to a controlled substance, has clear evidence of abuse potential and increasing incidence of abuse, and has shown evidence of a withdrawal syndrome with abrupt cessation from intake. This article will discuss the abuse potential of carisoprodol and the associated withdrawal syndrome, and consider implications for future use of the drug. PMID

  16. Improving Alcohol Withdrawal Outcomes in Acute Care

    PubMed Central

    Melson, Jo; Kane, Michelle; Mooney, Ruth; McWilliams, James; Horton, Terry

    2014-01-01

    Context Excessive alcohol consumption is the nation’s third leading cause of preventable deaths. If untreated, 6% of alcohol-dependent patients experience alcohol withdrawal, with up to 10% of those experiencing delirium tremens (DT), when they stop drinking. Without routine screening, patients often experience DT without warning. Objective: Reduce the incidence of alcohol withdrawal advancing to DT, restraint use, and transfers to the intensive care unit (ICU) in patients with DT. Design: In October 2009, the alcohol withdrawal team instituted a care management guideline used by all disciplines, which included tools for screening, assessment, and symptom management. Data were obtained from existing datasets for three quarters before and four quarters after implementation. Follow-up data were analyzed and showed a great deal of variability in transfers to the ICU and restraint use. Percentage of patients who developed DT showed a downward trend. Main Outcome Measures: Incidence of alcohol withdrawal advancing to DT and, in patients with DT, restraint use and transfers to the ICU. Results: Initial data revealed a decrease in percentage of patients with alcohol withdrawal who experienced DT (16.4%–12.9%). In patients with DT, restraint use decreased (60.4%–44.4%) and transfers to the ICU decreased (21.6%–15%). Follow-up data indicated a continued downward trend in patients with DT. Changes were not statistically significant. Restraint use and ICU transfers maintained postimplementation levels initially but returned to preimplementation levels by third quarter 2012. Conclusion: Early identification of patients for potential alcohol withdrawal followed by a standardized treatment protocol using symptom-triggered dosing improved alcohol withdrawal management and outcomes. PMID:24867561

  17. Driveway identification signing and marking

    SciTech Connect

    Not Available

    1986-09-01

    A primary purpose of a public highway is to provide access to commercial establishments. Driveways to fast-food restaurants, banks, retail stores, and office buildings line many road sections. A bewildering array of reflectorized, unreflectorized, lighted, and unlighted high- and low-mounted signs with varying messages direct motorists in and out of many of the driveways, while other access points have no signs. In a very few cases, the Manual of Uniform Traffic Control Devices-type signing for one-way roads has been installed for the one-way-type circulation design at some of these establishments. Should MUTCD-type one-way signs be recommended practice to control and provide a more uniform identification of these driveways when necessary. Are there signs not presently in the MUTCD that should be added to cope with this situation.

  18. Intra-administration associations and withdrawal symptoms: morphine-elicited morphine withdrawal.

    PubMed

    McDonald, Robert V; Siegel, Shepard

    2004-02-01

    On the basis of a conditioning analysis, some drug "withdrawal symptoms" are conditional responses elicited by stimuli paired with the drug effect. Prior demonstrations of conditional elicitation of withdrawal symptoms evaluated the role of environmental cues; however, pharmacological cues also typically signal a drug effect. Within each administration, early drug onset cues (DOCs) may become associated with the later, larger drug effect (intra-administration associations). This experiment evaluated the contribution of intra-administration associations to withdrawal symptoms. The results indicated that (a). 5 mg/kg morphine elicited behavioral and thermic withdrawal symptoms in rats previously injected on a number of occasions with 50 mg/kg morphine and that (b). DOC-elicited withdrawal symptoms are not a sensitized response to the opiate but rather an associative phenomenon. PMID:14769091

  19. Automatic Recognition of Road Signs

    NASA Astrophysics Data System (ADS)

    Inoue, Yasuo; Kohashi, Yuuichirou; Ishikawa, Naoto; Nakajima, Masato

    2002-11-01

    The increase in traffic accidents is becoming a serious social problem with the recent rapid traffic increase. In many cases, the driver"s carelessness is the primary factor of traffic accidents, and the driver assistance system is demanded for supporting driver"s safety. In this research, we propose the new method of automatic detection and recognition of road signs by image processing. The purpose of this research is to prevent accidents caused by driver"s carelessness, and call attention to a driver when the driver violates traffic a regulation. In this research, high accuracy and the efficient sign detecting method are realized by removing unnecessary information except for a road sign from an image, and detect a road sign using shape features. At first, the color information that is not used in road signs is removed from an image. Next, edges except for circular and triangle ones are removed to choose sign shape. In the recognition process, normalized cross correlation operation is carried out to the two-dimensional differentiation pattern of a sign, and the accurate and efficient method for detecting the road sign is realized. Moreover, the real-time operation in a software base was realized by holding down calculation cost, maintaining highly precise sign detection and recognition. Specifically, it becomes specifically possible to process by 0.1 sec(s)/frame using a general-purpose PC (CPU: Pentium4 1.7GHz). As a result of in-vehicle experimentation, our system could process on real time and has confirmed that detection and recognition of a sign could be performed correctly.

  20. Drug withdrawal conceptualized as a stressor

    PubMed Central

    Chartoff, Elena H.; Carlezon, William A.

    2015-01-01

    Drug withdrawal is often conceptualized as an aversive state that motivates drug-seeking and drug-taking behaviors in humans. Stress is more difficult to define, but is also frequently associated with aversive states. Here we describe evidence for the simple theory that drug withdrawal is a stress-like state, on the basis of common effects on behavioral, neurochemical, and molecular endpoints. We also describe data suggesting a more complex relationship between drug withdrawal and stress. As one example, we will highlight evidence that, depending on drug class, components of withdrawal can produce effects that have characteristics consistent with mood elevation. In addition, some stressors can act as positive reinforcers, defined as having the ability to increase the probability of a behavior that produces it. As such, accumulating evidence supports the general principles of opponent process theory, whereby processes that have an affective valence are followed in time by an opponent process that has the opposite valence. Throughout, we identify gaps in knowledge and propose future directions for research. A better understanding of the similarities, differences, and overlaps between drug withdrawal and stress will lead to the development of improved treatments for addiction, as well as for a vast array of neuropsychiatric conditions that are triggered or exacerbated by stress. PMID:25083570

  1. Inpatient management of acute alcohol withdrawal syndrome.

    PubMed

    Perry, Elizabeth C

    2014-05-01

    Alcohol withdrawal is a common condition encountered in the hospital setting after abrupt discontinuation of alcohol in an alcohol-dependent individual. Patients may present with mild symptoms of tremulousness and agitation or more severe symptoms including withdrawal seizures and delirium tremens. Management revolves around early identification of at-risk individuals and symptom assessment using a validated tool such as the revised Clinical Institute Withdrawal Assessment for Alcohol score. Benzodiazepines remain the mainstay of treatment and can be administered using a front-loading, fixed-dose, or symptom-triggered approach. Long-acting benzodiazepines such as chlordiazepoxide or diazepam are commonly used and may provide a smoother withdrawal than shorter-acting benzodiazepines, but there are no data to support superiority of one benzodiazepine over another. Elderly patients or those with significant liver disease may have increased accumulation and decreased clearance of the long-acting benzodiazepines, and lorazepam or oxazepam may be preferred in these patients. Patients with symptoms refractory to high doses of benzodiazepines may require addition of a rescue medication such as phenobarbital, propofol or dexmedetomidine. Anticonvulsants (carbamazepine, valproate, gabapentin) may have a role in the management of mild to moderate withdrawal. Other medications such as β-antagonists or neuroleptics may offer additional benefit in select patients but should not be used a monotherapy. PMID:24781751

  2. LSE-Sign: A lexical database for Spanish Sign Language.

    PubMed

    Gutierrez-Sigut, Eva; Costello, Brendan; Baus, Cristina; Carreiras, Manuel

    2016-03-01

    The LSE-Sign database is a free online tool for selecting Spanish Sign Language stimulus materials to be used in experiments. It contains 2,400 individual signs taken from a recent standardized LSE dictionary, and a further 2,700 related nonsigns. Each entry is coded for a wide range of grammatical, phonological, and articulatory information, including handshape, location, movement, and non-manual elements. The database is accessible via a graphically based search facility which is highly flexible both in terms of the search options available and the way the results are displayed. LSE-Sign is available at the following website: http://www.bcbl.eu/databases/lse/. PMID:25630312

  3. [Imaging signs in chest diagnostics].

    PubMed

    Krombach, G A

    2016-08-01

    Signs in chest imaging are defined as typical findings which can be easily recognized on x‑ray photographs or computed tomography (CT) scans of the chest. They are caused by different typical pathophysiological processes. Due to the association of a certain pathophysiological cause with a given sign, knowledge and use of these signs can allow the possible differential diagnoses to be narrowed down. If other imaging findings and clinical data are additionally taken into account, the diagnosis can be made with a high degree of confidence in many cases. PMID:27369549

  4. Drug withdrawals and the lessons within.

    PubMed

    Smith, Dennis A; Schmid, Esther F

    2006-01-01

    Drug withdrawals over recent decades have triggered changes in the way that drug targets and screening programs are researched and designed. In the cases having the greatest impact, the reason for withdrawal was the reversible interaction of a drug or its metabolite with a single receptor, ion channel or enzyme (primary or secondary pharmacology). Once this interaction is identified, screens can be established and validated. When the mechanism is complex (eg, organ toxicity), however, such screens are difficult to implement and usually examine only the initial step, leading to considerable problems in extrapolation and risk definition. This review classifies drugs withdrawn from the US market over the last 25 years by their reasons for withdrawal, and examines how drug discovery programs have been modified in response to these events. PMID:16445116

  5. Divalproex in the treatment of alcohol withdrawal.

    PubMed

    Myrick, H; Brady, K T; Malcolm, R

    2000-02-01

    The present study represents an open-label clinical trial comparing treatment with a benzodiazepine (lorazepam) to divalproex in 11 inpatients with uncomplicated alcohol withdrawal syndrome. The trial used the Clinical Institute Withdrawal Assessment for Alcohol-Revised (CIWA-Ar) scale. There were no significant differences in demographics or substance use parameters between the divalproex group (n = 6) or the lorazepam group (n = 5). A significant Group x CIWA-Ar score interaction [F(8,72) = 2.57, p < or = .01] was confirmed and further substantiated by a quadratic trend component for the interaction [F(1,9) = 24.9, p < or = .001]. This preliminary study supports further investigation of divalproex in the treatment of alcohol withdrawal. PMID:10718170

  6. Baclofen and Gamma-Hydroxybutyrate Withdrawal

    PubMed Central

    LeTourneau, Jennifer L.; Hagg, Daniel S.; Smith, Stephen M.

    2008-01-01

    Introduction Benzodiazepine treatment of life-threatening gamma-hydroxybutyrate (GHB) withdrawal is frequently unsatisfactory. Animal studies suggest strongly that treatment with GABAB agonists, such as baclofen, will be a more effective strategy. Methods A case report from the medical intensive care unit (ICU) of the university tertiary care hospital. Results A 61-year-old woman was admitted to the medical ICU for severe withdrawal symptoms from chronic GHB use. This manifested as delirium, tremor, and seizures despite only small decreases in GHB dose and treatment with benzodiazepines. The addition of baclofen allowed the rapid sequential decreases in the GHB dose without seizure or delirium and resulted in long-term improvement of her tremor. Conclusions Baclofen, a GABAB agonist, may be a useful agent in the treatment of severe GHB withdrawal. PMID:18266111

  7. Complications of alcohol withdrawal: pathophysiological insights.

    PubMed

    Trevisan, L A; Boutros, N; Petrakis, I L; Krystal, J H

    1998-01-01

    Disease processes or events that accompany acute alcohol withdrawal (AW) can cause significant illness and death. Some patients experience seizures, which may increase in severity with subsequent AW episodes. Another potential AW complication is delirium tremens, characterized by hallucinations, mental confusion, and disorientation. Cognitive impairment and delirium may lead to a chronic memory disorder (i.e., Wernicke-Korsakoff syndrome). Psychiatric problems associated with withdrawal include anxiety, depression, and sleep disturbance. In addition, alterations in physiology, mood, and behavior may persist after acute withdrawal has subsided, motivating relapse to heavy drinking. Recent advances in neurobiology may support the development of improved medications to decrease the risk of AW complications and support long-term sobriety. PMID:15706735

  8. Morphine withdrawal, treatments 1900-30.

    PubMed

    Malcolm, M T

    1999-03-01

    The treatments used between 1900 and 1930 for morphine withdrawal are discussed. The accounts are mainly taken from contemporary textbooks which contain fascinating descriptions of their authors' preferred methods and criticisms of regimes given by other therapists. Delirium, produced by atropine or similar substances, is advocated to cover withdrawal symptoms. The present paper draws parallels with current issues, e.g. withdrawal of opiate under cover of general anaesthesia, follow-up studies and cost-benefit analyses. The particular problems of addicted doctors in 1900-1930 are addressed as are the comparisons then made with non-medically qualified addicts. It is important we keep in mind past mistakes and over-valued ideas so as to reduce any similarly misplaced optimism in our current treatment options. PMID:11623818

  9. Withdrawal from long-term benzodiazepine treatment.

    PubMed Central

    Petursson, H; Lader, M H

    1981-01-01

    Long-term, normal-dose benzodiazepine treatment was discontinued in 16 patients who were suspected of being dependent on their medication. The withdrawal was gradual, placebo-controlled, and double-blind. All the patients experienced some form of withdrawal reaction, which ranged from anxiety and dysphoria to moderate affective and perceptual changes. Symptom ratings rose as the drugs were discontinued, but usually subsided to prewithdrawal levels over the next two to four weeks. Other features of the withdrawal included disturbance of sleep and appetite and noticeable weight loss. Electroencephalography showed appreciable reduction in fast-wave activity as the drugs were withdrawn, and an improvement in psychological performance was recorded by the Digit Symbol Substitution Test. Because of the risk of dependence on benzodiazepines these agents should probably not be given as regular daily treatment for chronic anxiety. PMID:6114776

  10. Neurotoxic Consequences of Chronic Alcohol Withdrawal: Expression Profiling Reveals Importance of Gender Over Withdrawal Severity

    PubMed Central

    Hashimoto, Joel G; Wiren, Kristine M

    2011-01-01

    While women are more vulnerable than men to many of the medical consequences of alcohol abuse, the role of sex in the response to ethanol is controversial. Neuroadaptive responses that result in the hyperexcitability associated with withdrawal from chronic ethanol likely reflect gene expression changes. We have examined both genders for the effects of withdrawal on brain gene expression using mice with divergent withdrawal severity that have been selectively bred from a genetically heterogeneous population. A total of 295 genes were identified as ethanol regulated from each gender of each selected line by microarray analyses. Hierarchical cluster analysis of the arrays revealed that the transcriptional response correlated with sex rather than with the selected withdrawal phenotype. Consistent with this, gene ontology category over-representation analysis identified cell death and DNA/RNA binding as targeted classes of genes in females, while in males, protein degradation, and calcium ion binding pathways were more altered by alcohol. Examination of ethanol-regulated genes and these distinct signaling pathways suggested enhanced neurotoxicity in females. Histopathological analysis of brain damage following ethanol withdrawal confirmed elevated cell death in female but not male mice. The sexually dimorphic response was observed irrespective of withdrawal phenotype. Combined, these results indicate a fundamentally distinct neuroadaptive response in females compared to males during chronic ethanol withdrawal and are consistent with observations that female alcoholics may be more vulnerable than males to ethanol-induced brain damage associated with alcohol abuse. PMID:17593928