ABSTRACT
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.
Subject(s)
Receptors, Dopamine/metabolism , Receptors, GABA/metabolism , Stress, Physiological/metabolism , Animals , Benzazepines/pharmacology , Dopamine Antagonists/pharmacology , Drug Interactions , Feeding Behavior/drug effects , GABA Agonists/pharmacology , Male , Muscimol/pharmacology , Psychomotor Performance/drug effects , Rats , Rats, Sprague-Dawley , Receptors, Dopamine/drug effects , Receptors, GABA/drug effectsABSTRACT
Experiments were conducted to evaluate the possibility that central GABA(A) receptors are involved in the stress response of rats. Separate groups of animals were implanted bilaterally with cannulae in the lateral cerebral ventricle, substantia nigra, and anterior to the rostral margin of the substantia nigra. Microinjections of the GABA(A) agonist muscimol into each of these areas augmented the stress response evoked by moderate tail pinch. Although consistent changes in the amount of food eaten in response to stress were not observed, stress-evoked gnawing was significantly increased by muscimol at all three sites. Additionally, intraventricular muscimol resulted in an enhancement of stress-evoked oral stereotypy, revolution (escape behavior), and vocalization. The data suggest that a GABAergic component exists in the central mediation of stress. The results are discussed in regard to possible interactions between GABA and central dopamine systems.
