Differences in the nature of the stereotyped behaviour induced by aporphine derivatives in the rat and in their actions in extrapyramidal and mesolimbic brain areas

Abstract

Apomorphine, (-)-N-n-propylnorapomorphine [(-)-NPA] and (±)-N-n-propylnorapomorphine [(±)-NPA] each caused stereotyped behaviour patterns in the rat which could be differentiated into two components, sniffing and repetitive head and limb movements (low intensity component) and gnawing, biting and licking (high intensity component). Low intensity components occurred at low doses of apomorphine and high intensity components at larger doses but the two components never occurred independently for (-)-NPA or (±)-NPA. Biting was the predominant effect of these agents which were shown to be at least twenty times more potent than apomorphine. The (-)-isomer of NPA was the more potent. The two components of stereotypy were differentiated both pharmacologically (using amantadine, reserpine plus α-methyl-p-tyrosine and haloperidol) and by lesions placed in areas of the extrapyramidal (caudate-putamen, globus pallidus, substantia nigra) and mesolimbic (nucleus accumbens septi, tuberculum olfactorium, nucleus amygdaloideus centralis) systems. However, both sniffing and biting responses were reduced by lesions of the serotonergic raphe nuclei. The two stereotypic components were differentially induced by intracerebral injections of apomorphine and (-)-NPA into the caudate-putamen, nucleus accumbens septi and tuberculum olfactorium. Injections into the central nucleus of the amygdala were ineffective. The degree of involvement of the different areas was shown to differ for apomorphine and (-)-NPA, in particular the nucleus accumbens septi appeared more important for the action of (-)-NPA and the tuberculum olfactorium for apomorphine. Intracaudate (-)-NPA was less active than apomorphine but, generally, intracerebrally applied (-)-NPA was twice as potent as apomorphine. Both (-)-NPA and apomorphine caused circling behaviour in animals with asymmetric medial raphe nucleus lesions (contralateral) or unilateral lesions of the substantia nigra (ipsilateral). In these experiments (-)-NPA was ten times more potent than apomorphine.