title: Neurochemical substrates for opiate reinforcement.
abstract: The studies reported herein summarize our work to date aimed at determining the neurochemical substrates for the reinforcing properties of opiates. Rats were trained to self-administer heroin intravenously in daily 3-hour sessions, and pharmacological blockade and neurotoxin-induced lesions were used to define the neurochemical substrates for this reinforcing action. Low-dose DA receptor blockade failed to alter heroin self-administration but significantly increased cocaine self-administration, presumably reflecting a decrease in the reinforcing effectiveness of cocaine. Destruction of presynaptic DA terminals within the N.Acc. produced extinction of cocaine, but not heroin, self-administration. Opiate receptor blockade with systemic naloxone increased heroin, but not cocaine, self-administration. Methylnaloxonium injections into the N.Acc. were effective in increasing heroin self-administration at doses one-eighth those observed for intracerebroventricular injections. Reinforcement has been explored using a place-preference procedure and a self-administration drug-substitution paradigm. Mu/delta agonists such as B-END readily produce a naloxone-reversible place preference. Fentanyl derivatives also produce place preference and substitute for heroin during self-administration. The kappa agonist U50-488 produces place aversion, not place preference, and does not readily substitute for heroin. Altogether, these results suggest that mu/delta receptor subtypes in the region of the N.Acc. may be an important neurochemical substrate for opiate reinforcement.
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000187:drug effects / Q000502:physiology*; D001931:Brain Mapping; D004298:Dopamine / Q000502:physiology; D003932:Heroin / Q000494:pharmacology; D009294:Narcotics / Q000494:pharmacology*; D009714:Nucleus Accumbens / Q000502:physiology; D051381:Rats; D011954:Receptors, Dopamine / Q000502:physiology; D011957:Receptors, Opioid / Q000145:classification / Q000187:drug effects / Q000502:physiology; D012054:Reinforcement, Psychology / Q000502:physiology*; D012646:Self Administration
chemical_list: D009294:Narcotics; D011954:Receptors, Dopamine; D011957:Receptors, Opioid; D003932:Heroin; D004298:Dopamine