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 facil itate stress responding and GABA is known to modulate central dopaminergic activity. To evaluate the possibility that this effect of muscimol may depe nd upon a dopamine mechanism we have tested the effect of intracerebroventr icular coadministration of muscimol and the selective D-1 antagonist SCH 23 390 on behaviors evoked by tail pinch stress. When injected by themselves m uscimol (1.75 nmol) facilitated stress-evoked oral behavior while SCH 23390 (6-600 nmol) produced a dose-related suppression of oral behavior. Coadmin istration of muscimol and doses of SCH 23390 selected for producing no (6 a nd 30 nmol), or marginal (60 nmol), effects on stress responding resulted i n a dose-related reversal of the increase in orality seen with muscimol alo ne. The results are consistent with the notion that stressful stimuli activ ate central GABA(A) systems which, in turn, enhance dopaminergic neurotrans mission. (C) 2000 Elsevier Science Inc.