Disinhibition of nigral GABA output neurons mediates muscular rigidity elicited by striatal opioid receptor stimulation

Abstract

Unilateral injection of bicuculline (12.5-50 ng) into the substantia nigra pars reticulata (SNR) dose-dependently produced a tonic activity in the electromyogram (EMG), which was antagonized by coadministered muscimol. Bilateral lesions of the caudate nucleus with kainic acid failed to affect the EMG activity produced by unilateral injection of bicuculline into the SNR. Administration of muscimol (12.5 and 25 ng) into the SNR antagonized the tonic activity in the EMG produced by morphine (15 mg/kg i.p.), whereas bicuculline (50 ng) enhanced it. These results suggest that an impairment in the GABAergic neurotransmission in the SNR is relevant for mediating the tonic activity in the EMG produced by morphine and that GABAergic mechanisms in the SNR play an important role in the modulating the opioid-induced alterations in the striatal function.