Differential effects of dorsal raphe lesions and intraraphe GABA and benzodiazepines on conflict behavior in rats.
Both reductions in brain serotonin activity and injections of benzodiazepine drugs increase punished responding in rats, but the evidence is conflicting on the role of serotonin pathways in the benzodiazepine effect. Therefore a series of studies were carried out using a Geller-Seifter procedure with three components, to examine drug effects on rewarded, nonrewarded, and punished responding. Using male hooded Lister rats and chronic indwelling cannulae, it was found that neither chlordiazepoxide (1.5 and 5.0 micrograms in 0.5 microliter), midazolam (1.0 and 10.0 micrograms in 0.5 microliter), nor GABA (100, 500, 1000, and 5000 ng in 0.5 microliter), exerted significant anticonflict activity when injected into the dorsal raphe. Lesions of the dorsal raphe produced by injections of 5,6-dihydroxytryptamine significantly increased punished responding, and there were significant correlations between lesion size, extent of forebrain serotonin depletion, and increases in punished responding. Peripheral injections of chlordiazepoxide (5.0 and 10.0 mg/kg) and midazolam (1.25, 2.5, and 5.0 mg/kg) significantly increased punished responding both before and after raphe lesions. The increase in lesioned animals was significantly greater than after drug or lesion alone and represented a powerful additive effect which was specific to punished responding. As intraraphe benzodiazepines did not exert significant anticonflict activity, and raphe lesions did not attenuate the anticonflict activity of peripheral benzodiazepines, it is concluded that increases in punished responding seen after serotonin depletion and after benzodiazepine drugs may be dissociable.
D015115:5,6-Dihydroxytryptamine / Q000494:pharmacology; D000818:Animals; D001569:Benzodiazepines / Q000494:pharmacology; D002707:Chlordiazepoxide / Q000494:pharmacology*; D003220:Conflict, Psychological; D008297:Male; D008874:Midazolam; D011903:Raphe Nuclei / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D012701:Serotonin / Q000502:physiology; D009435:Synaptic Transmission; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology* / Q000502:physiology
D001569:Benzodiazepines; D012701:Serotonin; D005680:gamma-Aminobutyric Acid; D002707:Chlordiazepoxide; D008874:Midazolam; D015115:5,6-Dihydroxytryptamine