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)

Evidence of a role for GABA in benzodiazepine effects on food preference in rats.

It has previously been shown that chronic treatment with the GABA-transaminase inhibitor ethanolamine-O-sulphate (EOS), which elevates brain GABA levels by around 200%, selectivity enhances novel food consumption in rats treated with chlordiazepoxide (CDP) and given a food preference test. To replicate and extend these findings, the effects of two doses of CDP with and without EOS pretreatment were compared with those of EOS or saline alone. EOS alone had no significant effects except to decrease eating rate but, in combination with 2.5 mg/kg CDP, it antagonised the increase in weight of familiar food eaten found with CDP alone and marginally increased weight eaten and duration of novel foot eating episodes. EOS magnified the effects of 5.0 mg/kg CDP to increase markedly the weight eaten and duration of episodes for novel chocolate drops. As no additive effects of EOS and CDP on rate of eating were found, the results are consistent with a facilitation of novel food consumption by an anxiolytic action of the two drugs, rather than by a rate-retarding action which might bias animals toward novel food. Finally, that EOS alone did not mimic the effects of CDP suggests that the role of GABA in the anxiolytic action of CDP may be indirect.

Effects of chronic chlordiazepoxide treatment on novel and familiar food preference in rats.

Chlordiazepoxide (CDP) given acutely has been found to have dose-related effects in rats given food preference tests. Low doses selectively increase consumption of familiar food, while high doses increase novel food consumption. The present study examined the effects of three doses of CDP given chronically. All doses (2.5, 5.0 and 10.0 mg/kg) selectively increased novel food eating. There was some evidence for a selective retardation of eating rate for familiar food and an enhanced taste preference for sweet food in CDP-treated rats. However, the overall results suggest that increased consumption of novel food represents an antineophobic action of CDP, which is potentiated by chronic treatment over a low to medium dose range.