Psychopharmacology
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Dysregulation of the brain serotonergic system has been implicated in the pathophysiology of violence and aggression. As a key regulator of central serotonergic activity, dysfunction of the serotonin transporter (5-HTT) represents a potential mechanism mediating pathological aggression. ⋯ Deletion of the 5-HTT gene produces a reduction in aggressive behavior and home cage activity. Desensitization of 5-HT(1A/1B) receptor function may contribute to reduced aggression in 5-HTT KO mice.
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Acute morphine and abstinence from chronic morphine have been shown to increase and to decrease extracellular dopamine (DA) in the nucleus accumbens, respectively. In contrast, extracellular DA in the prefrontal cortex (PFC) is not modified by acute morphine and is markedly increased during abstinence syndrome. ⋯ The results suggest that: a) morphine-stimulated DA release from DA terminals is compensated by reduced DA release from NA terminals; b) morphine abstinence-induced inhibition of DA release from DA terminals is overshadowed by a marked increase in DA released from NA terminals. Thus, the paradoxical response of PFC DA to morphine and morphine abstinence may be explained by the fact that extracellular DA in the PFC mainly represents the amine co-released from NA terminals.
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Endogenous opioids have been implicated in the hedonic evaluation of food and palatability. Opioids may also be involved in alcohol intake, as there is a positive correlation between alcohol drinking and preference for sweets and fats. Our previous studies have shown that mu opioid stimulation of the nucleus accumbens preferentially augments intake of palatable food containing sucrose and fat. ⋯ These results provide evidence to suggest that the mu opioid system within the ventral striatum regulates ingestive behavior via a mechanism related to the hedonic assessment of taste. In addition, the nucleus accumbens may be a key brain area where ethanol interacts with endogenous opioid systems, and thus may be a common neural substrate for both food palatability and alcohol drinking.
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Comparative Study Clinical Trial Controlled Clinical Trial
Blockade of hydromorphone effects by buprenorphine/naloxone and buprenorphine.
Buprenorphine is an opioid agonist-antagonist used in the treatment of opioid dependence. Naloxone has been combined with buprenorphine to decrease the parenteral abuse potential of buprenorphine. This addition of naloxone may also confer further opioid blockade efficacy. ⋯ The addition of naloxone to buprenorphine may deter the parenteral abuse of buprenorphine/naloxone, but it does not enhance the therapeutic efficacy of buprenorphine. The blockade efficacy of buprenorphine/naloxone is dose related; however, doses up to 32/8 mg buprenorphine/naloxone provide only partial blockade when subjects receive a high dose of an opioid agonist.
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Randomized Controlled Trial Comparative Study Clinical Trial
Maintaining alertness and performance during sleep deprivation: modafinil versus caffeine.
The performance and alertness effects of modafinil were evaluated to determine whether modafinil should replace caffeine for restoring performance and alertness during total sleep deprivation in otherwise healthy adults. ⋯ Like caffeine, modafinil maintained performance and alertness during the early morning hours, when the combined effects of sleep loss and the circadian trough of performance and alertness trough were manifest. Thus, equivalent performance- and alertness-enhancing effects were obtained with drugs possessing different mechanisms of action. However, modafinil does not appear to offer advantages over caffeine (which is more readily available and less expensive) for improving performance and alertness during sleep loss in otherwise normal, healthy adults.