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Hypocretin-1 and -2 (Hcrt-1 and Hcrt-2), also referred to as orexin-A and -B, are neuropeptides synthesized by a few thousand neurons in the lateral hypothalamus. Hypocretin-containing neurons project throughout the brain, with a prominent input to basal forebrain structures involved in motivation, reward, and stress. However, the role of hypocretins in(More)
BACKGROUND There has been a recent upsurge of interest in the role of hypothalamic feeding peptides, in particular, orexin (hypocretin), in drug-seeking behavior. However, the potential role of other hypothalamic feeding peptides, such as cocaine- and amphetamine-regulated transcript (CART), in conditioned reinstatement has yet to be explored. METHODS(More)
Metabotropic glutamate receptors (mGluRs) have been implicated in regulating anxiety, stress responses, and the neurobehavioral effects of psychostimulants. The present study sought to determine whether group II mGluR activation by the potent mGlu2/3 receptor agonist, (-)-2-oxa-4-aminobicylco hexane-4,6-dicarboxylic acid (LY379268), antagonizes(More)
The conditioning of cocaine's pharmacological actions with environmental stimuli is thought to be a critical factor in long-lasting relapse risk associated with cocaine addiction. To study the significance of environmental stimuli in enduring vulnerability to relapse, the resistance to extinction of drug-seeking behavior elicited by a cocaine-related(More)
Major precipitating factors for relapse to drug use are stress and exposure to drug-related environmental stimuli. Group II (mGlu(2/3)) metabotropic glutamate receptors (mGluRs) are densely expressed within circuitries mediating the motivating effects of stress and drug cues and, therefore, may participate in regulating drug-seeking linked to both of these(More)
This study examined whether nociceptin/orphanin FQ (NC), the endogenous ligand of the opioid receptor-like1 (ORL1) receptor, can block drug-seeking behavior induced by foot-shock stress. Male Wistar rats were trained to operantly self-administer ethanol or cocaine, and then subjected to daily extinction training until responding ceased. Subsequent exposure(More)
BACKGROUND Rats with extended daily cocaine access show escalating cocaine self-administration and behavioral signs of dependence. Regulation of glutamatergic transmission by metabotropic glutamate receptors has emerged as a mechanism in the addictive actions of drugs of abuse. We examined here whether neuroadaptive dysregulation of metabotropic glutamate(More)
This study examined the effects of a nonselective opiate antagonist and antagonists selective for the mu(1) versus delta opioid receptor on ethanol-seeking behavior induced by alcohol-related environmental stimuli in an animal model of relapse. Rats were trained to self-administer ethanol (10% w/v) or water on an FR 1 schedule in 30-min daily sessions. The(More)
To advance understanding of the potential of metabotropic glutamate receptor (mGluR) 5 as treatment targets for cocaine addiction, the effects of MTEP [3-[(2-methyl-1,3-thiazol-4-yl) ethynyl]piperidine] (a selective mGluR5 antagonist) on conditioned reinstatement of cocaine seeking were examined. To test whether modification of conditioned reinstatement by(More)
Stress-like symptoms are an integral part of acute and protracted drug withdrawal, and several lines of evidence have shown that dysregulation of brain stress systems, including the extrahypothalamic corticotropin-releasing factor (CRF) system, following long-term drug use is of major importance in maintaining drug and alcohol addiction. Recently, two other(More)