GABA in the deep layers of the superior colliculus/mesencephalic reticular formation mediates the enhancement of startle by the dopamine D1 receptor agonist SKF 82958 in rats

Abstract

GABA transmission in the deep layers of the superior colliculus/deep mesencephalic reticular formation (deep SC/Me) mediates several motor responses, including those expressed after systemic administration of dopamine agonists. In the present study we examined the role of the deep SC/Me in the modulation of the acoustic startle reflex and its enhancement by the dopamine D1 agonist SKF 82958. Rats were implanted with bilateral cannulas into the deep SC/Me or superficial layers of the SC (super SC) and I week later were infused with various compounds. The GABA(A) antagonist bicuculline (0, 5, and 10 ng) produced a dose-and time-dependent enhancement of startle after infusion into the deep SC/Me, but not the super SC. Infusion of the GABA(A) agonist muscimol (0.1 μg) into the deep SC/Me, but not the super SC, blocked the enhancement of startle by systemic SKF 82958 (1 mg/kg) but had no effect on baseline startle by itself. This effect was not produced by infusion of the D1 antagonist SCH 23390(1 μg) or the glutamate antagonist NBQX (0.1 μg). Deposits of FluoroGold into the deep SC/Me, combined with immunohistochemistry for glutamic acid decarboxylase (GAD), confirmed a direct GABAergic input from the substantia nigra pars reticulata (SNr) to the deep SC/Me. These results suggest that GABA tone in the deep SC/Me modulates the expression of startle as well as the enhancement of startle by dopamine D1 agonists. On the basis of these data and previous work, we have proposed a striatonigral-tectal-reticular neural pathway mediating the effects of dopamine D1 agonists on startle.