mu Opioid control of the N-methyl-D-aspartate-evoked release of [H-3]-acetylcholine in the limbic territory of the rat striatum in vitro: Diurnal variations and implication of a dopamine link

Using an in vitro microsuperfusion procedure, the release of newly synthesized [H-3]-acetylcholine (ACh), evoked by N-methyl-D-aspartate (NMDA) receptor stimulation, was investigated in striosome-enriched areas and matrix of the rat striatum. The role of mu-opioid receptors, activated by endogenously released enkephalin, on the NMDA-evoked release of ACh was studied using the selective mu-opioid receptor antagonist, beta-funaltrexamine. Experiments were performed 2 (morning) or 8 (afternoon) h after light onset, in either the presence or absence (alpha-methyl-p-tyrosine, an inhibitor of dopamine synthesis) of dopaminergic transmission. As expected, based on the presence of mu-opioid receptors in striosomes, beta-funaltrexamine (0.1 nM, 10 nM and 1 muM) enhanced the NMDA (1 mM + 10 muM D-serine)evoked release of ACh in striosome-enriched areas but not in the matrix. Interestingly, these responses were significantly more pronounced in afternoon than in morning experiments. In the presence of alpha-methyl-p-tyrosine, the NMDA-evoked release of ACh was increased with similar amplitude in morning and afternoon experiments. However, in this condition (without dopamine transmission), the facilitatory effects of beta-funaltrexamine on the NMDA-evoked release of ACh were suppressed totally in the morning and only partially in the afternoon. The selective mu-opiate agonist, [D-Ala(2), N-Me-Phe(4),Gly(5)-ol]-enkephalin (1 muM, coapplied with NMDA), was without effect on the NMDA-evoked release of ACh but abolished both dopamine-dependent (morning) and dopamine-independent (afternoon) responses of beta-funaltrexamine (10 nM and 1 muM). Therefore, in the limbic territory of the striatum enriched in striosomes, the mu-opioid-inhibitory regulation of ACh release follows diurnal rhythms. While dopamine is required for this regulation in the morning and the afternoon, an additional dopamine-independent process is present only in the afternoon. (C) 2003 IBRO. Published by Elsevier Ltd. All rights reserved.