The effect of bromocriptine on locomotor activity and cerebral catecholamines in rodents.

Abstract

Abstract The locomotor activity in mice induced by bromocriptine was suppressed by drugs inhibiting both dopaminergic and noradrenergic pre- and post-synaptic actions. The onset of locomotor activity was preceded by a period of decreased activity which lengthened with increasing dose. Both increased and decreased turnover of noradrenaline and decreased turnover of dopamine was shown by measurement of the dopamine metabolites homovanillic acid, dihydroxyphenylacetic acid (DOPAC) and the noradrenaline metabolite MOPEG-SO4 and following pretreatment of animals with α-methyl-p-tyrosine. The increased activity caused by bromocriptine did not correlate with a consistent biochemical change, but the period of behavioural suppression appeared to be associated with an increased noradrenaline turnover. Bromocriptine potently inhibited the noradrenaline-stimulated adenylate cyclase system from mouse limbic forebrain suggesting that the increased in vivo turnover of noradrenaline may be due to a post-synaptic receptor blockade. The involvement of cerebral dopamine receptors was substantiated by the ability of bromocriptine to displace [3H]haloperidol from binding sites in rat striatal preparations. The findings are interpreted as indicating a complex involvement of both noradrenaline and dopamine pre-and post-synaptic components in the locomotor activity produced by bromocriptine, possibly due to the involvement of a partial agonist action or an active metabolite.