Psychopharmacology
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We evaluated the effects of haloperidol and its metabolites on capsaicin-induced mechanical hypersensitivity (allodynia) and on nociceptive pain induced by punctate mechanical stimuli in mice. ⋯ These results show that haloperidol and its metabolites I and II produce antiallodynic but not antinociceptive effects against punctate mechanical stimuli and suggest that their antiallodynic effect may be due to blockade of sigma(1) receptors but not to dopamine receptor antagonism.
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The novel antidepressant, agomelatine, behaves as an agonist at melatonin MT(1) and MT(2) receptors and as an antagonist at serotonin (5-HT)(2C) receptors. In animal models and clinical trials, agomelatine displays antidepressant properties and re-synchronizes disrupted circadian rhythms. ⋯ Agomelatine possesses a distinctive EEG profile compared with melatonin, ramelteon, and S32006, possibly reflecting co-joint agonist and antagonist properties at MT(1)/MT(2) and 5-HT(2C) receptors, respectively.
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Craving is a primary feature of opiate addiction and is clinically significant because of its potential to trigger opiate use and relapse. Opiate use can also produce abnormal pain perception. We predicted that for opiate addicts (OAs), there may be an association between these two major features of addiction (drug craving and abnormal pain responses). ⋯ A hyperalgesic state persists for at least 5 months in abstinent OAs and is predictive of cue-induced craving. Longitudinal research is needed to clarify the direction of causation between hyperalgesia and opiate addiction.
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Comparative Study
Behavioral effects and pharmacokinetics of gamma-hydroxybutyrate (GHB) precursors gamma-butyrolactone (GBL) and 1,4-butanediol (1,4-BD) in baboons.
Gamma-butyrolactone (GBL) and 1,4-butanediol (1,4-BD) are prodrugs for gamma-hydroxybutyrate (GHB). Like GHB, GBL and 1,4-BD are drugs of abuse, but their behavioral effects may differ from GHB under some conditions. ⋯ GBL and 1,4-BD produced behavioral effects similar to those previously reported with GHB and the time course of effects were related to blood levels of GHB. Given their higher potency and faster onset of effects, the abuse liability of GBL and 1,4-BD may be greater than GHB.
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Vulnerability for weight gain is an individual trait. Obese people undertake dieting, but permanent weight loss is difficult to attain due to repeated phases of relapse to excess consumption. ⋯ The results show for the first time that withdrawal from free-choice HFHS induces craving that is specific to the OP animals and suggests that OP individuals may have withdrawal symptoms that are similar to those induced by addictive drugs.