Homovanillic acid concentration in rat brain: effect of a choline acetyltransferase inhibitor and comparison with cholinergic and dopaminergic agents.

Abstract

Administration to rats of either atropine sulphate (5 mg/kg, i.p.) or 4-(1-naphthylvinyl) pyridine HCl (100 mg/kg, i.p.), an inhibitor of choline acctyltransferase, decreased the concentration of homovanillic acid in the corpus striatum by 50 per cent, as measured 1 hr later. The decrease in homovanillic acid induced by administration of either agent was prevented by pretreatment (10 min earlier) with either pilocarpine HCl (10 mg/kg, i.p.) or eserine sulphate (1.25 mg/kg, i.p.). Administration of apomorphine HCl (5 mg/kg, i.p.) or (+)-amphetamine sulphate (5 mg/kg. i.p.) also lowered the concentration of homovanillic acid. In contrast to the effects produced by atropine or naphthylvinyl pyridine, however, the decrease in homovanillic acid induced by treatment with either apomorphine or amphetamine was not reversed by pretreatment with either pilocarpine or eserine. Administration of either mecamylamine HCl (15 mg/kg, i.p.), atropine methylnitrate (5 mg/kg, i.p.) or neostigmine methylsulphatc (0.2 mg/kg, i.p.) had no effect on the level of homovanillic acid. These results suggest that naphthylvinyl pyridine possesses central anticholinergic activity similar to that of atropine. Furthermore, the cholinergic effect on the metabolism of dopamine in the corpus striatum appears to be mediated via muscarinic receptors in the central nervous system.