Evidence against the involvement of serotonergic neurons in the anti-punishment activity of diazepam in the rat.
The effects of manipulating central serotonergic transmission were assessed on the anti-punishment effects of diazepam (2 mg/kg IP) in rats. In a paradigm involving the inhibition of pressing for food induced by the delivery of a signal previously associated with electric foot-shocks, lesioning serotonergic neurons of the dorsal raphé with the neurotoxin 5,7-dihydroxytryptamine (5,7-DHT; 1 microgram in 0.4 microliter) neither affected behavioral inhibition in control rats nor modified the ability of diazepam to release responding. Furthermore, suppression of pressing for food induced by a fixed ratio 7 schedule of shock presentation was reduced by bilateral infusion of 5,7-DHT (2 micrograms in 0.5 microliter) into the substantia nigra, but the ability of diazepam to increase punished responding was preserved. Finally, blockade of benzodiazepine-induced decrease in serotonin release by application of the benzodiazepine receptor antagonist Ro 15-1788 (10(-5)-10(-4)M in 0.2 microliter) into the dorsal raphé did not alter the releasing effect of diazepam on suppression of pressing for food caused by a signal of punishment. At these concentrations. Ro 15-1788 was devoid of any effect on behavioral inhibition in control rats. Taken together, these results indicate that the anti-punishment activity of benzodiazepines can be dissociated from the reduction in tryptaminergic transmission produced by these drugs.
D015116:5,7-Dihydroxytryptamine / Q000494:pharmacology*; D000818:Animals; D001570:Benzodiazepinones / Q000494:pharmacology; D003216:Conditioning, Operant / Q000187:drug effects*; D003975:Diazepam / Q000494:pharmacology*; D004102:Dihydroxytryptamines / Q000494:pharmacology*; D004597:Electroshock; D005442:Flumazenil; D007267:Injections; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D011678:Punishment; D011903:Raphe Nuclei; D051381:Rats; D011919:Rats, Inbred Strains; D012055:Reinforcement Schedule; D012701:Serotonin / Q000502:physiology*; D013378:Substantia Nigra
D001570:Benzodiazepinones; D004102:Dihydroxytryptamines; D015116:5,7-Dihydroxytryptamine; D012701:Serotonin; D005442:Flumazenil; D003975:Diazepam