Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
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Neuropsychopharmacology · Jun 2009
Operant sensation seeking engages similar neural substrates to operant drug seeking in C57 mice.
Novelty and sensation seeking have been associated with elevated drug intake in human and animal studies, suggesting overlap in the circuitry mediating these behaviors. In this study, we found that C57Bl/6J mice readily acquired operant responding for dynamic visual stimuli, a phenomenon we term operant sensation seeking (OSS). Like operant studies using other reinforcers, mice responded on fixed and progressive ratio schedules, were resistant to extinction, and had sustained responding with extended access. ⋯ Finally, we found that one common measure of novelty seeking, locomotor activity in a novel open field, did not predict OSS performance. OSS may have predictive validity for screening compounds for use in the treatment of drug addiction. In addition, we also discuss the potential relevance of this animal model to the field of behavioral addictions.
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Neuropsychopharmacology · Jun 2009
Prefrontal GABA(B) receptor activation attenuates phencyclidine-induced impairments of prepulse inhibition: involvement of nitric oxide.
Recent theories propose that both GABA and glutamate signaling are compromised in patients with schizophrenia. These deficits can be observed in several brain regions including the prefrontal cortex (PFC), an area extensively linked to the cognitive dysfunction in this disease and notably affected by NMDA receptor antagonists such as phencyclidine (PCP). We have previously demonstrated that inhibition of the nitric oxide (NO) pathways in the brain, particularly in the PFC, prevents a wide range of PCP-induced behavioral deficits including disruption of prepulse inhibition (PPI). ⋯ Additionally, baclofen decreased NO release in the PFC in a dose-related manner. This study proposes a role for GABA(B) receptor signaling in the effects of PCP, with altered NO levels as a downstream consequence. Thus, prefrontal NO signaling mirrors an altered level of cortical inhibition that may be of importance for information processing deficits in schizophrenia.