Brain Research, 523 (1990) 51-56 51 Elsevier BRES 15700 Effect of opioids on acetylcholine release evoked by K ÷ or glutamic acid from rat neostriatal slices Ernest Arenas, Jordi Alberch, Ricardo Sanchez Arroyos and Jordi Marsal Departament de Biologia CeLlular i Anatomia Patolrgica, Facuhat de Medicina, Laboratori de Neurobiologia CeLlular i Molecular, Universitat de Barcelona, Barcelona (Spain) (Accepted 23 January 1990) Key words: Glutamate; Acetylcholine release; Opiate; Naloxone; Tetrodotoxin; Neostriatum Endogenous acetylcholine (ACh) release from rat striatal slices was measured by a chemiluminescent method. Several opiate agents were tested for their ability to modulate ACh release evoked by potassium ions (K ÷) or glutamic acid (GLU). Morphine, [D-Ala2, Gly(ol)5]-enkephalin (DAGO), [D-Ala2,o-LeuS]-enkephalin (DADLE) and [D-PenLD-PenS]-enkephalin (DPDPE) were found to have an inhibitory effect on K +- or GLU-evoked ACh release. This effect was completely blocked by naloxone, but this antagonist by itself had no effect on ACh release. The action of/~-opiate agonists (morphine and DAGO) on ACh release evoked by K + was sensitive to tetrodotoxin (qTX), but that of 6-opiate agonists (DADLE and DPDPE) was insensitive. The release evoked by GLU was abolished in the presence of TTX. The activation of r-opiate receptor by dynorphin-(1-13) had no effect on K ÷- or GLU-evoked ACh release. It is concluded that/~- and 6-opiate agonists, but not r, exert an inhibitory control on striatal cholinergic interneurons, but with a different mechanism of action or localization of the receptors. Corticostriatal glutamatergic neurons have an important role in the interaction of the ACh-opioid systems. INTRODUCTION The presence of multiple classes of opiate receptors has been demonstrated in brain,/~-, 6- and r-types have been extensively studied and defined 12'28. The neostria- tum contains a large number of enkephalinergic and dynorphinergic neurons, as well as high density of receptors for these opiate peptides 3'3°'46. Autoradio- graphic studies have indicated that r- and 6-binding sites are homogeneously distributed in the striatum, whereas g-opiate receptors are more concentrated in patches 3° complementary to a rich acetylcholinesterase staining matrix~4,19,25 Acetylcholinesterase intense perikarya of the striatum are large aspiny neurons that account for approximately 1-8% of all striatal neurons 26'31. Furthermore, these cells have been identified by choline acetyltransferase immu- noreactivity as cholinergic interneurons 22'31. Opioid interactions with cholinergic neurons are known. However, data on effects of opioid drugs on acetylcholine (ACh) release are conflicting. Mulder and coworkers 33 found that the activation of h-receptors inhibited [14C]ACh release from rat striatal slices, in contrast with other findings 21. Also p-receptor agonists have shown different effects on ACh release: facilita- tory 4'45, inhibitory 4 or no effect 33'44. Thus, it remains to be definitively established the type(s) of opioid recep- tor(s) involved in the modulation of ACh release in the striatum. The striatum receives a massive input from frontal cortex and other somatosensory cortices 6'x°, which is electrophysiologically excitatory in nature 43. The projec- tions are believed to utilize glutamate (GLU) as a neurotransmitter. Significant reductions in the levels of GLU, in its high-affinity uptake and in the K+-evoked release of GLU have been found in the striatum of rats with lesions of the cerebral cortex 11. Moreover, elec- trophysiological studies have revealed that corticostriatal pathway seems to establish monosynaptic inputs with neostriatal neurons 23,24. Later, morphological studies have shown that aspiny dendrites of presumptive cholin- ergic striatal interneurons receive cortical inputs 17'18. Furthermore, excitatory amino acids are known to release ACh from rat striatum 2,27,42. The aim of the present study was to examine whether K ÷- or GLU-stimulated ACh release is modulated in a different manner by p-, 6- and r-opiate agents. Endoge- nous ACh release was continuously detected by a chemiluminescent method. Correspondence: J. Marsal, Department de Biologia Cel.lular i Anatomia Patolbgica, Facultat de Medicina, Universitat de Barcelona, Casanovas 143, 08036-Barcelona, Spain. 0006-8993/90/$03.50 © 1990 Elsevier Science Publishers B.V. (Biomedical Division)