Role of the substantia nigra pars reticulata in sensorimotor gating, measured by prepulse inhibition of startle in rats

The substantia nigra pars reticulata (SNR) is one of the major output nucle i of the basal ganglia. It connects the dorsal and ventral striatum with th e thalamus, superior colliculus and pontomedullary brainstem. The SNR is th erefore in a strategic position to regulate sensorimotor behavior. We here assessed the effects of SNR lesions on prepulse inhibition (PPI) of the aco ustic startle response (ASR), stereotypy and locomotion in drug-free rats, as well as after systemic administration of the dopamine agonist DL-ampheta mine (2 mg/kg), and the NMDA receptor antagonists dizocilpine (0.16 mg/kg) and CGP 40116 (2 mg/kg). SNR lesions reduced PPI, enhanced spontaneous snif fing and potentiated the locomotor stimulation by dizocilpine and CGP 40116 . PPI was impaired by dizocilpine and CGP 40116 in controls. The ASR was en hanced in controls by dizocilpine and amphetamine. SNR lesions prevented th e enhancement of the ASR by amphetamine. A second experiment tested the hyp othesis that the SNR mediates PPI via a GABAergic inhibition of the startle pathway. Infusion of the GABA, antagonist phaclofen but not the GABA, anta gonist picrotoxin into the caudal pontine reticular nucleus reduced PPI. He nce, lesion of the SNR reduces sensorimotor gating possibly by elimination of a nigroreticular GABAergic projection interacting with GABA, receptors. Moreover, destruction of the SNR enhances the motor stimulatory effects of amphetamine and of the NMDA antagonists dizocilpine and CGP 40116. We concl ude that the SNR exerts a tonic GABAergic inhibition on sensorimotor behavi or that is regulated by the dorsal and the ventral striatum. (C) 2000 Elsev ier Science B.V. All rights reserved.