Metabolite involvement in the behavioral effects of bromocriptine in cats

Abstract

There is a lag phase of 30–60 min before the onset of bromocriptine (BC) action. This delay may be necessary for the formation of active metabolites. The objective was to determine whether the abnormal behavioral effects induced by BC involve active hepatic metabolites. Thus, we studied the effect of an inhibitor of hepatic hydroxylation metabolism (SKF 525A) on the behavior of BC-treated cats. Experiments began after six weeks of habituation and involved i.p. injections of: (1) propylene glycol (drug vehicle); (2) SKF 525A (70 mg/kg); (3) BC (10 mg/kg); and (4) SKF 525A followed 30 min later by BC. Each cat received the four treatments with two weeks elapsing between consecutive experiments. The frequency of 12 behaviors was scored for 60 min after 1 h posttreatment. BC alone induced emergent behavioral changes (hallucinatory-like, limb flicks, abortive grooms) that were not observed following control injections (vehicle and SKF 525A). There was a complete elimination of BC-induced hallucinatory-like behavior/escape by SKF 525A pretreatment. Other emergent behaviors were similarly reduced but persisted in all cats. The large frequency of grooming induced by BC was significantly reduced. SKF 525A pretreatment was correlated with a significant increase in staring and quiet sitting and a failure of BC to increase activities such as rubbing, treading and kneading. But many other BC-induced behaviors showed no changes. The data demonstrated that particular BC-induced changes in cats are antagonized by SKF 525A. The behavioral suppression caused by SKF 525A is compatible with the involvement of active hepatic metabolites from BC. The findings suggest that hepatic metabolites resulting from hydroxylation, rather than hydrolysis, of the BC parent molecule are responsible for the hallucinatory-like behavior/escape.