Collicular picrotoxin alleviates akinesia but not sensory neglect in rats with bilateral 6-hydroxydopamine lesions of ventral midbrain

Abstract

Anatomical and biochemical investigations have suggested that GABA transmission in the superior colliculus consequent upon activity of the nigrotectal pathway is increased following 6-hydroxydopamine (6-OHDA) lesions of the ascending dopamine systems. Moreover, it has been proposed that this increase in inhibitory activity within the colliculus may be responsible for the sensory neglect commonly observed after dopamine denervation. The present experiment sought to test this proposal by examining the effects of injections of the GABA antagonist picrotoxin into the superior colliculus of 6-OHDA lesioned rats, in the hope that the neglect caused by the 6-OHDA would be reversed. However, in 33 of 36 cases studied intracollicular microinjections of picrotoxin produced no detectable improvement in orientation to sensory stimuli, although a wide range of other behavioural effects was observed. These included stereotyped exploratory movements (e.g. head waving, walking, sniffing and rearing) similar to those produced in the 6-OHDA treated rats by systemic injection of apomorphine (0.1 mg/kg). These data indicate that 6-OHDA lesions of substantia nigra and ventral midbrain areas do not produce sensory neglect simply by increasing GABA transmission within the nigrotectal pathway. Instead, such an increase in nigrotectal activity may impair production of particular kinds of movement, possibly related to exploratory behaviour.