INTERMITTENT AND CHRONIC MORPHINE TREATMENT INDUCES LONG-LASTING CHANGES IN DELTA-OPIOID RECEPTOR-REGULATED ACETYLCHOLINE-RELEASE IN RAT STRIATUM AND NUCLEUS-ACCUMBENS

Intermittent treatment of rats with morphine (10 mg/kg s.c., once dail y) caused an increase (of about 30%) of the electrically evoked releas e of [C-14]acetylcholine from cholinergic interneurons of superfused s triatal slices 1-21 days after morphine withdrawal. Similarly, chronic treatment with escalating doses of morphine (5-50 mg/kg s.c., 3 times daily), causing physical dependence (unlike intermittent treatment), resulted in an enduring enhanced response of these neurons towards dep olarization. Following chronic morphine treatment this adaptive increa se of acetylcholine release was associated with a slight but long-last ing decrease of the (delta-opioid receptor-mediated) maximal inhibitor y effect of [Met(5)]enkephalin, whereas upon intermittent drug treatme nt delta-opioid receptor desensitization was observed 1 day after opia te withdrawal only. Also in slices of the nucleus accumbens both inter mittent as well as chronic morphine administration caused a long-lasti ng increase of the electrically evoked [C-14]acetylcholine release. Th erefore, we hypothesize that an enhanced (re)activity of striatal and accumbal cholinergic neurons, which are regulated by dopaminergic neur ons of the ventral mesencephalon, may represent a long-lasting neuroad aptive effect of morphine (and possibly other drugs of abuse) playing a crucial role in behavioral sensitization associated with enhanced vu lnerability to drugs of abuse.