Manipulation of central GABAergic and dopaminergic systems alters stress responding in the rat

Activation of central GABA(A) systems with muscimol has been shown to facilitate stress responding and GABA is known to modulate central dopaminergic activity. To evaluate the possibility that this effect of muscimol may depend upon a dopamine mechanism we have tested the effect of intracerebroventricular coadministration of muscimol and the selective D(1) antagonist SCH 23390 on behaviors evoked by tail pinch stress. When injected by themselves muscimol (1.75 nmol) facilitated stress-evoked oral behavior while SCH 23390 (6-600 nmol) produced a dose-related suppression of oral behavior. Coadministration of muscimol and doses of SCH 23390 selected for producing no (6 and 30 nmol), or marginal (60 nmol), effects on stress responding resulted in a dose-related reversal of the increase in orality seen with muscimol alone. The results are consistent with the notion that stressful stimuli activate central GABA(A) systems which, in turn, enhance dopaminergic neurotransmission.