Psychopharmacology
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Administration of 5-hydroxytryptamine (5-HT)1A and 5-HT2A receptor agonists into the dorsal periaqueductal gray (DPAG) inhibits escape, a defensive behavior associated with panic attacks. Long-term treatment with the antipanic compound imipramine enhances the DPAG 5-HT1A- and 5-HT2A-receptor-mediated inhibition of escape, implicating these receptors in the mode of action of panicolytic drugs. ⋯ The results suggest that facilitation of the 5-HT1A- and 5-HT2A-receptor-mediated inhibition of DPAG neuronal activity is implicated in the beneficial effect of antidepressants in panic disorder.
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Randomized Controlled Trial Comparative Study Clinical Trial
Thermoregulatory effects of 3,4-methylenedioxymethamphetamine (MDMA) in humans.
Although 3,4-methylenedioxymethamphetamine (MDMA; Ecstasy) has been reported to cause fatal hyperthermia, few studies of the effects of MDMA on core body temperature in humans have been conducted demonstrating increased body temperature. In rats, MDMA causes hyperthermia at warm ambient temperatures but hypothermia at cold ones. ⋯ Unlike findings in rats, MDMA increased core body temperature regardless of ambient temperature in humans. These increases appeared related to increases in metabolic rate, which were substantial. These findings warrant further investigations on the role of MDMA and other stimulants in altering metabolism and thermogenesis.
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Randomized Controlled Trial Comparative Study Clinical Trial
A double-blind, placebo- and positive-internal-controlled (alprazolam) investigation of the cognitive and psychomotor profile of pregabalin in healthy volunteers.
Pregabalin potently and selectively binds to the alpha(2)-delta subunit of voltage-dependent calcium channels, reducing calcium influx and modulating release of downstream excitatory neurotransmitters, such as glutamate. Pregabalin has demonstrated robust efficacy for several disease states, but its neuropharmacology is still being elucidated. ⋯ Pregabalin did not differ on most assessments from placebo, producing only minor, transient impairment on some objective cognitive and psychomotor measures, suggesting a relatively benign CNS side-effect profile.
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Comparative Study
ACP-103, a 5-HT2A/2C inverse agonist, potentiates haloperidol-induced dopamine release in rat medial prefrontal cortex and nucleus accumbens.
Atypical antipsychotic drugs (APDs) such as clozapine, olanzapine, quetiapine, risperidone, and ziprasidone are serotonin (5-HT)(2A) antagonists and relatively weaker dopamine (DA) D(2) antagonists, with variable 5-HT(2C) antagonist properties. The ability of atypical APDs to preferentially increase DA release in the cortex compared to the limbic system is believed to be due in part to their antagonism of 5-HT(2A) and D(2) receptors and believed to contribute to their beneficial effects on cognition, negative, and psychotic symptoms. Previous studies from this laboratory using microdialysis have shown that pretreatment of the 5-HT(2A) antagonist M100907 with the typical APD and D(2) antagonist haloperidol produced an increase in the medial prefrontal cortex (mPFC), but not in the nucleus accumbens (NAC), DA release. However, pretreatment with the 5-HT(2A/2C) receptor antagonist SR46349-B with haloperidol increased both mPFC and NAC DA release, suggesting that both 5-HT(2A) and 5-HT(2C) properties may be important for atypical APD effects. ⋯ These data suggest that the relative extent of 5-HT(2A) and 5-HT(2C) antagonism, as well as the extent of D(2) receptor blockade, has a critical influence on DA release in the mPFC and NAC and may be a determining factor in the action of this class of atypical APDs on these two potentially clinically relevant parameters.
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Dopamine signaling in the nucleus accumbens (NAc) plays an important role in regulating drug-taking and drug-seeking behaviors, but the role of D(1)- and D(2)-like receptors in this regulation remains unclear. ⋯ Both D(1) and D(2) receptors in the NAc play a prominent, and perhaps cooperative, role in regulating cocaine-taking and cocaine-seeking behaviors.