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

Abstract

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 μmol/l) inhibited the stimulation-evoked overflow, and this effect was blocked by the muscarine receptor antagonists atropine (0.1 μmol/l) and pirenzepine (1 μmol/l) in all experimental groups to the same extent. The δ-receptor selective opioid peptide [ d-Pen 2, d-Pen 5]enkephalin (0.3 μmol/l) inhibited [ 3H]acetylcholine release in all groups, although its effect was smaller in grafts than in normal tissue. The preferential μ-receptor agonist [ d-Ala 2, N-methyl-Phe 4,Gly-ol 5]enkephalin also reduced [ 3H]acetylcholine release in all groups, but only at the high concentration of 10 μmol/l. The effect of both drugs was antagonized by naloxone (1 μmol/l). The preferential к-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 δ receptors. The enhancement by к-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.