Evidence for the involvement of brain GABA and serotonin systems in the anticonflict effects of chlordiazepoxide in rats.
Using male hooded Lister rats the effects of GABAergic and serotonergic treatments alone and with chlordiazepoxide (CDP) were compared with the behavioral effects of CDP in a conditioned conflict procedure with three components; Reward, Time Out, and Conflict. CDP (2.5, 5.0, and 10.0 mg/kg ip) dose- relatedly increased punished and time out responding, but increased rewarded responding in an inversely dose-related manner. Punished responding was enhanced by chronic treatment to a rate which remained stable between 9 and 19 injections. The GABA transaminase inhibitor ethanolamine-O-sulfate (EOS), given chronically in drinking water (5.0 mg/ml), increased punished responding linearly to a high stable level after 2-3 weeks. Rewarded and time out responding were less substantially increased. CDP given with EOS dose- relatedly increased time out and punished responding substantially above the rates found with either treatment alone. The GABA antagonist picrotoxin blocked the increase in punished and time out responding found with EOS and CDP alone. The tryptophan hydroxylase inhibitor p-chlorophenylalanine (PCPA; 100 mg/kg x 3) linearly increased punished responding for the first week of treatment. CDP with PCPA selectively and significantly increased punished responding above the rates for either treatment alone, but the increases were not as substantial as those with EOS + CDP. The serotonin reuptake inhibitor Wy 25093 reduced increases in time out and punished responding under CDP, and the precursor 5-hydroxytryptophan (5-HTP) counteracted increases in punished responding under PCPA but also substantially reduced rewarded responding. These results provide evidence that both increased GABA and decreased serotonin transmission are involved in the anticonflict effects of CDP, as EOS and PCPA both mimicked and potentiated effects of CDP, while picrotoxin, Wy 25093, and 5-HTP counteracted them.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D001921:Brain / Q000502:physiology*; D002707:Chlordiazepoxide / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D003220:Conflict, Psychological; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004983:Ethanolamines / Q000008:administration & dosage; D007211:Indoles / Q000008:administration & dosage; D008297:Male; D010852:Picrotoxin / Q000008:administration & dosage; D051381:Rats; D012701:Serotonin / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects; D013997:Time Factors; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D002707:Chlordiazepoxide; D004983:Ethanolamines; D007211:Indoles; D010852:Picrotoxin; D012701:Serotonin; D005680:gamma-Aminobutyric Acid; C029142:Wy 25093; C020619:ethanolamine O-sulfate