Anti-conflict and depressant effects by GABA agonists and antagonists, benzodiazepines and non-gabergic anticonvulsants on self-stimulation and locomotor activity

Abstract

Rats were injected systemically with different classes of gabergic agent in order to investigate gabergic involvement in limbic output. Agonists differed one from another in their effects on variable-interval self-stimulation: clonazepam (in repeatedly-tested rats), chlordiazepoxide and pentobarbitone had a strongly biphasic action, low doses being facilitatory and high doses depressant, whereas other agonists including valproate and 3-APS (homotaurine) were uniformly depressant. The facilitatory effects of the benzodiazepines were dramatically enhanced by GABA antagonists (picrotoxin or pentylenetetrazol) even though antagonists on their own produced a dose-dependent depression that was not reversible by other anticonvulsant drugs. Ventral tegmental electrode placements yielded generally similar results. Depression of self-stimulation observed on initial exposure to clonazepam was reversed by repeated self-stimulation testing in the drugged state but not by repeated daily injections without testing. Locomotor activity (under conflict-free conditions) was unaffected or was depressed both by agonists and by antagonists. Thus, the facilitation of self-stimulation by chlordiazepoxide, pentobarbitone and clonazepam appears to be accounted for in terms of non-gabergic anti-conflict activity by these agents. Self-stimulation and locomotor changes following systemic administration did not disclose facilitatory effects attributable to gabergic efferents from limbic dopamine areas.