Attenuation of amphetamine-induced motor stimulation and stereotypy by 6-hydroxydopamine in the rat.

1. In accord with previous reports, intraventricular administration of 6-hydroxydopamine (250 mug) to rats did not influence spontaneous locomotor activity. Neither was the stereotyped behaviour seen after high doses of (+)-amphetamine (5 mg/kg) changed by this treatment. Increases in motor activity induced by (+)-amphetamine (0.5 and 1.0 mg/kg) were significantly reduced after 6-hydroxydopamine.2. When 6-hydroxydopamine (250 mug) was administered to tranylcypromine (5 mg/kg) pretreated animals, spontaneous activity was significantly reduced. The stimulant effects of (+)-amphetamine (0.5 and 1.0 mg/kg) were completely abolished and amphetamine stereotypy (5.0 mg/kg) was absent or reduced after this treatment.3. Bilateral injections of 6-hydroxydopamine (10 mug) into the substantia nigra abolished the more pronounced features of amphetamine stereotypy. However, although significantly reduced, amphetamine-induced locomotor stimulation was observed in these animals. Spontaneous activity was also reduced.4. These observations suggest that dopaminergic nigro-striatal neurones mediate some of the stimulant effects of amphetamine as well as being of critical importance in amphetamine-induced stereotypy. However, other catecholaminergic neurones also appear to be involved in amphetamine motor stimulation. The results are consistent with the view that amphetamine exerts its behavioural effects indirectly through its action on brain catecholamines.