Psychopharmacology
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Comparative Study
Effects of kappa-opioid receptor ligands on intracranial self-stimulation in rats.
Elevations in cAMP response element binding protein (CREB) function within the mesolimbic system of rats reduce cocaine reward in place conditioning studies and increase immobility in the forced swim test. Each of these behavioral adaptations can be interpreted as a depressive-like effect (i.e., anhedonia, despair) that may reflect reduced activity of brain reward systems. Furthermore, each effect appears due to increases in CREB-mediated expression of dynorphin, since each is attenuated by intracranial injections of the kappa-opioid receptor antagonist norBNI. ⋯ These data provide further evidence that stimulation of brain kappa-receptors may trigger certain depressive-like signs, and that kappa antagonists may have efficacy as antidepressants without having reward-related actions of their own.
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Comparative Study
Effects of three hypnotics on the sleep-wakefulness cycle in sleep-disturbed rats.
New sleep disturbance model in rats is useful for estimating the characteristics of some hypnotics. ⋯ The present insomnia model can be used as a sleep disturbance model for testing not only the sleep-inducing effects but also the sleep-maintaining effects including non-REM sleep and REM sleep of hypnotics.
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Clinical Trial Controlled Clinical Trial
Ketamine impairs response inhibition and is positively reinforcing in healthy volunteers: a dose-response study.
Ketamine is an N-methyl-D-aspartate (NMDA) receptor antagonist that has medical indications but is also used as a recreational drug. Previous research has found persisting cognitive and psychotogenic effects of ketamine in chronic abusers of this drug 3 days after an acute dose. ⋯ The lack of residual effects in healthy volunteers on day 3 indicates that impairments found on day 3 in ketamine abusers are chronic effects. The abuse of ketamine may be related to its capacity both to reinforce and to decrease response inhibition.
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Low platelet monoamine oxidase (MAO) activity is associated with problem drinking and other deviant behaviors. Since the majority of alcohol abusers are smokers, and tobacco smoke has a direct inhibitory effect on the enzyme, these associations may not be meaningful. ⋯ These findings demonstrate that platelet MAO activity is lower in subjects with socially deviant behavior, and the association of low platelet MAO and problem drinking is not an artifact of smoking.
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Exaggerated acoustic startle is a prominent symptom of post-traumatic stress disorder (PTSD); however, its physiological basis is not well understood, and there are few available treatments. Neurobiological research has suggested that anti-kindling agents and/or glutamate antagonists can attenuate the acoustic startle response (ASR) in animal models. The anticonvulsant topiramate is an AMPA antagonist that also demonstrates potent anti-kindling effects and may, therefore, have promise in treating trauma-enhanced ASR. ⋯ The current results provide one of the few demonstrations of a single stress episode producing sustained enhancement of ASR. In addition, topiramate demonstrates promise in treating exaggerated acoustic startle symptoms in PTSD or other stress-related disorders.