PHARMACOLOGICAL CHARACTERIZATION OF NEURONAL ACETYLCHOLINE GATED ION-CHANNEL RECEPTOR-MEDIATED HIPPOCAMPAL NOREPINEPHRINE AND STRIATAL DOPAMINE RELEASE FROM RAT-BRAIN SLICES

Neuronal acetylcholine-gated ion channel receptor-mediated [H-3]-norep inephrine [H-3]-NE) and [H-3]-dopamine [H-3]-DA) release from rat hipp ocampal and striatal slices, respectively, were compared. The nicotini c receptor agonists (-)-nicotine, (-)-cytisine and 1,1-dimethyl-4-phen ylpiperazinium iodide (DMPP) increased both [H-3]-NE and [H-3]-DA rele ase in a concentration-dependent manner. The rank order of potency for the three agonists was DMPP > (-)-cytisine > (-)-nicotine for evoking [H-3]-NE release and (-)-cytisine>DMPP = (-)-nicotine for releasing [ H-3]-DA. (-)-Cytisine acted as a partial agonist in stimulating DA rel ease as it displayed lower efficacy and inhibited the agonistic effect of (-)-nicotine. (-)-Cytisine and (-)-nicotine were equally effective in stimulating NE release. The responses to a maximally effective con centration of (-)-nicotine, (-)-cytisine or DMPP on [H-3]-NE release w ere blocked by 1 mu M tetrodotoxin (TTX). In contrast, the effects of the various agonists on [H-3]-DA release were not blocked by tetrodoto xin. The nicotinic receptor antagonists, d-tubocurarine (3-100 mu M) a nd mecamylamine (1.0-10 mu M) blocked the H-3-NE release induced by (- )-nicotine and DMPP in the rat hippocampal slice, whereas dihydro p-er ythroidine (3-300 mu M) was without effect. In the striatum, mecamylam ine (0.3-10 mu M) and dihydro p-erythroidine (3-100 mu M) blocked the responses mediated by both agonists whereas d-tubocurarine (3-100 mu M ) was ineffective. We conclude that the subtype(s) of neuronal acetylc holine-gated ion channel receptors mediating striatal [H-3]-DA release are different from those mediating hippocampal [H-3]-NE release.