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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: BACKGROUND, OBJECTIVE, METHODS, RESULTS. Meshes: Animals, Cocaine, Cocaine-Related Disorders, Conditioning, Operant, Corpus Striatum, Dopamine D2 Receptor Antagonists, Extinction, Psychological, Infusions, Intravenous, Male, Microinjections, Nitriles, Nucleus Accumbens, Rats, Rats, Long-Evans, Receptors, Dopamine D2, Receptors, Dopamine D3, Reinforcement (Psychology), Secondary Prevention, Self Administration, Stress, Psychological, Substance Withdrawal Syndrome, Tetrahydroisoquinolines.
user
Does blockade of mesolimbic dopamine D3 receptors inhibit stress-induced reinstatement of cocaine-seeking in rats? Context: The dopamine (DA) D3 receptor is preferentially expressed in the mesolimbic system. We have previously shown that selective D3 receptor blockade by the novel D3 antagonist SB-277011A inhibits cocaine's reinforcing action and cocaine-induced reinstatement of cocaine-seeking behavior. In the present study, we investigated whether SB-277011A similarly inhibits stress-induced reinstatement of cocaine-seeking behavior. Rats were allowed to self-administer cocaine (0.5 mg/kg per infusion, 3 h per session) for 10-14 days, followed by a once-daily extinction session for 7-14 days during which saline was substituted for cocaine. Extinction criteria were fewer than ten lever-presses per 3-h session for at least 3 consecutive days. After cocaine-seeking behavior was extinguished, each animal was tested twice for footshock-stress-induced reinstatement, once with vehicle (25% hydroxypropyl-beta-cyclodextrin) and once with one of three doses of SB-277011A in counterbalanced fashion. During the last 3 days of cocaine self-administration (SA), active lever-presses were approximately 100 per session under fixed-ratio 2 reinforcement (approximately 25 mg/kg cocaine per session). After extinction, intermittent footshock (10 min, 0.5 mA, 0.5 s on with a mean inter-shock interval of 40 s) robustly reinstated the cocaine-seeking behavior (8.4+/-3.6 active lever-presses in last extinction session to 35.3+/-5.2 in animals after footshock stress). Intraperitoneal (i.p.) injections of SB-277011A (3, 6, and 12 mg/kg) dose-dependently blocked stress-induced reinstatement of cocaine-seeking. Reinstatement was also blocked by microinjections of SB-277011A (1.5 microg/0.5 microl per side) bilaterally into the nucleus accumbens, but not into the dorsal striatum.
assistant
The mesolimic DA D3 receptor plays an important role in mediating stress-induced reinstatement. Final Decision: yes