Behavioural effects in the rat after acute unilateral intranigral infusions of N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine

Abstract

N-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induced a dose-dependent contralateral circling in the rat when infused unilaterally into the central region of the pars reticulata of the substantia nigra. This action of MPTP seems to be nigral dopamine-mediated since rotation was potentiated by intranigral amphetamine (50 micrograms unilaterally) and blocked by haloperidol (5 micrograms bilaterally) as well as by picrotoxin (5 micrograms bilaterally) and by unilateral lesions of the internal capsule. MPTP was not effective in inducing rotation in rats with unilateral 6-hydroxydopamine lesions of the median forebrain bundle in contrast to intranigral apomorphine which produced robust turning. The data suggest that MPTP may not act as a dopamine receptor agonist but induce rotation by other mechanisms, for example, by enhancing the accumulation of dopamine release from dendrites in the pars reticulata.