The effects of globus pallidus lesions on dopamine-dependent motor behaviour in rats.

Motor effects of bilateral lesions of the globus pallidus induced by quinolinic acid (30 and 60 nmol in 0.5 microl) were investigated in rats. Globus pallidus lesions with 60 nmol quinolinic acid produced a significant reduction of spontaneous motor activity measured by a reduced locomotor activity in an open field and by a reduced sniffing activity in an experimental chamber. In addition, D-amphetamine (1 mg/kg, i.p.)-induced hyperlocomotion and D-amphetamine (3 mg/kg, i.p.)-induced stereotyped sniffing were significantly reduced in animals with quinolinic acid lesions (60 nmol). Globus pallidus lesions with 60 nmol quinolinic acid potently reversed catalepsy induced by systemic administration of the dopamine D1 receptor antagonist SCH23390 (0.75 and 1 mg/kg, i.p.) or the dopamine D2 receptor antagonist raclopride (1.25 and 5 mg/kg, i.p.), while lesions with 30 nmol quinolinic acid exerted anti-cataleptic effects which were only partly significant. In line with current models of basal ganglia functions, these findings indicate that inactivation of the globus pallidus reduced spontaneous motor activity and motor hyperactivity after dopamine receptor stimulation. However, the present data also demonstrate that inactivation of the globus pallidus reversed motor hypoactivity induced by a blockade of dopamine D1 and D2 receptors. Therefore, a more complex functional model of the globus pallidus is required to account for the opposite effects on motor behaviour observed after lesions of this basal ganglia nucleus.