Psychopharmacology
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Broad evidence indicates that modulation of the glutamatergic system could be an efficient way to achieve antidepressant activity. Metabotropic glutamate receptor (mGlu receptor) ligands seem to be promising agents to treat several central nervous system disorders, including psychiatric ones. ⋯ These results strongly suggest that activation of the mGlu7 receptor elicits antidepressant-like effects.
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Randomized Controlled Trial
Single and multiple doses of rimonabant antagonize acute effects of smoked cannabis in male cannabis users.
A single 90-mg dose of the cannabinoid CB1 receptor antagonist rimonabant attenuates effects of smoked cannabis in humans. ⋯ Repeated lower daily rimonabant doses (40 mg) attenuated the acute physiological effects of smoked cannabis to a similar degree as a single 90-mg dose; repeated 40-mg doses attenuated subjective effects after 8 but not 15 days.
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Low capacity of the central serotonergic system has been associated with impulsive behaviour. Both low platelet monoamine oxidase (MAO) activity and the short (S) allele of the serotonin transporter gene promoter region polymorphism (5-HTTLPR) are proposed to be markers of less efficient serotonergic functioning. ⋯ The two markers of lower serotonergic capacity, 5-HTTLPR S allele and low platelet MAO activity, have a similar and partly synergistic influence on self-reported as well as performance measures of impulsivity.
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Catalepsy is a preclinical test that predicts extrapyramidal symptoms in humans. It models symptoms of acute extrapyramidal side effects induced at the beginning of antipsychotic treatment. Nitric oxide (NO) plays a role in a series of neurobiological functions underlying behavior. For example, inhibition of NO synthesis disrupts rodent exploratory behavior and induces catalepsy. Although several effects mediated by NO involve the activation of soluble guanylyl cyclase (sGC), the transduction mechanism of the catalepsy-inducing effect of NO has not yet been investigated. ⋯ This study showed that pharmacological disruption of the endogenous NO-sGC signaling in the central nervous system induces long-lasting catalepsy in mice. Moreover, the cataleptic effect of NOS inhibition correlates with the decrease in NO( x ) products formation in the striatum. The results give further support to the hypothesis that NO plays a role in motor behavior control mediated, at least in part, by cyclic guanosine monophosphate production in the striatum.
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Randomized Controlled Trial Comparative Study
Modest opioid withdrawal suppression efficacy of oral tramadol in humans.
Tramadol is in an unscheduled atypical analgesic with low rates of diversion and abuse and mixed pharmacologic actions, including modest opioid agonist activity. ⋯ Tramadol 200 and 400 mg show evidence of opioid withdrawal suppression without significant observer- and subject-rated opioid agonist effects. The profile of action did not suggest a high risk for tramadol abuse in opioid dependent individuals. Tramadol may be a useful medication for treating opioid withdrawal.