Dopaminergic stimulants and cyclic nucleotides in mouse brain. Effects of dopaminergic antagonists, cholinolytics, and GABA agonists

Abstract

The effects of dopaminergic stimulants on the cyclic GMP content in the medial forebrain and the cerebellum were studied in mice pretreated with dopaminergic antagonists, cholinolytics and agents enhancing GABAergic transmission. Low doses of butyrophenones (haloperidol and spiroperidol) inhibited the rise in cyclic GMP levels and the stereotyped behaviour induced by amphetamine, but were without effect on the same biochemical and behavioural changes elicited by apomorphine. Higher doses effectively blocked the rise in cyclic GMP levels and the stereotyped behaviour elicited by both drugs. These findings suggest that low doses of the dopaminergic antagonists may predominantly act by interfering with the release of dopamine from presynaptic stores, while high doses may act by blockade of the postsynaptic dopaminergic receptor. The rise in cerebellar cyclic GMP levels elicited by dopaminergic stimulants appears not to involve cholinergic transmission, since atropine did not block the effects of the dopaminergic stimulants. Enhancement of GABAergic transmission by diazepam or aminooxyacetic acid antagonized the rise in cerebellar cyclic GMP content induced by the dopaminergic stimulants, but was without effect on the cyclic GMP content in the medial forebrain. Cyclic AMP levels were not affected by any of the drugs in both parts of the brain.