Stereotyped behaviour patterns and hyperactivity induced by amphetamine and apomorphine after discrete 6-hydroxydopamine lesions of extrapyramidal and mesolimbic nuclei

Abstract

Changes in stereotyped sniffing, biting and hyperactivity induced by apomorphine and d-amphetamine in the rat were determined after bilateral 6-hydroxydopamine (6-OHDA) lesions (8–16 μg/4 μl) of the extrapyramidal caudate-putamen (CP) (anterior and centre), globus pallidus (GP) and substantia nigra (SN), the mesolimbic nucleus accumbens (ACB), tuberculum olfactorium (TUO) and central amygdaloid nucleus (ACE). Lesions were also induced in the medial forebrain bundle in the lateral hypothalamus (LH). The 6-OHDA lesions of the CP reduced amphetamine biting but not sniffing or hyperactivity. Centrally placed 6-OHDA failed to modify any response to apomorphine but anterior locations reduced apomorphine biting. Both lesion locations led to a 45–65% reduction in striatal dopamine (DA) content, but the anterior location also involved depletions of mesolimbic DA. 6-OHDA lesions of the GP reduced striatal DA by 62% but initially potentiated before reducing both apomorphine and amphetamine biting. These lesions also potentiated amphetamine hyperactivity but other parameters were unmodified. The LH and SN lesions reduced striatal and mesolimbic DA by 75–80% and potentiated apomorphine biting. The LH lesions reduced amphetamine biting and hyperactivity but the SN lesions initially potentiated these responses. 6-OHDA lesions of the ACB reduced the DA content of this nucleus by 72% but had little effect on the TUO: these lesions reduced the duration of amphetamine hyperactivity and potentiated apomorphine biting. In contrast, equally selective lesions of the TUO (80% DA depletion) enhanced the locomotor activity response to both apomorphine and amphetamine; apomorphine biting was also increased but other parameters were unmodified. Lesions of the ACE depleted amygdaloid DA by at least 80% and reduced or abolished apomorphine and amphetamine biting in the chronic stage. The results indicate that the sites for mediation of stereotyped sniffing, biting or hyperactivity are not the same for apomorphine and amphetamine, and that each behavioural state involves the functioning of more than one DA-containing area.