title: 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.
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D000927:Anticonvulsants / Q000494:pharmacology*; D001569:Benzodiazepines; D003220:Conflict, Psychological; D004305:Dose-Response Relationship, Drug; D018756:GABA Antagonists; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D012653:Self Stimulation; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
chemical_list: D014151:Anti-Anxiety Agents; D000927:Anticonvulsants; D018756:GABA Antagonists; D001569:Benzodiazepines; D005680:gamma-Aminobutyric Acid