Modulation by muscarine and opioid receptors of acetylcholine release in slices from striato-striatal grafts in the rat.

The accumulation of tritium during incubation with [3H]choline and the subsequent efflux of tritium were studied in striatal slices from non-operated rats, in striatal slices from animals which had received a contralateral striatal ibotenic acid lesion, and in slices from striato-striatal suspension grafts, 16-31 weeks after implantation into previously lesioned striata. In graft slices, the accumulation of tritium as well as the overflow of tritium evoked by electrical stimulation (360 pulses, 3 Hz) was much smaller than in slices from non-operated controls. The muscarine receptor agonist oxotremorine (0.1-1 micromol/l) inhibited the stimulation-evoked overflow, and this effect was blocked by the muscarine receptor antagonists atropine (0.1 micromol/l) and pirenzepine (1 micromol/l) in all experimental groups to the same extent. The delta-receptor selective opioid peptide [D-Pen2, D-Pen5]enkephalin (0.3 micromol/l) inhibited [3H]acetylcholine release in all groups, although its effect was smaller in grafts than in normal tissue. The preferential mu-receptor agonist [D-Ala2,N-methyl-Phe4,Gly-ol5]enkephalin also reduced [3H]acetylcholine release in all groups, but only at the high concentration of 10 micromols/l. The effect of both drugs was antagonized by naloxone (1 micromol/l). The preferential kappa-receptor agonist ethylketocyclazocine enhanced the stimulation-evoked overflow in non-operated animals, an effect abolished by naloxone and also by sulpiride. In grafts, ethylketocyclazocine caused no change. It is concluded that acetylcholine release in striato-striatal grafts can be modulated by muscarine autoreceptors and by opioid delta receptors. The enhancement by kappa-receptor activation of [3H]acetylcholine release in non-operated striata depends on a dopaminergic input to the cholinergic cells which does not exist in grafts.