Serotoninergic control of punished behavior: effects of intra-raphe microinjections of chlordiazepoxide, GABA and 5-HT on behavioral suppression in rats.
The effects of intra dorsalis raphe microinjections of chlordiazepoxide, GABA and 5-HT were studied on a model of behavioral suppression in rats. The suppression of responding for food was elicited by a 10 min presentation of a signal previously associated with the delivery of electric foot shocks. Microinjections of chlordiazepoxide, GABA and 5-HT (0.2 microliters) performed in awake hand-held rats reduced the behavioral suppression. Chlordiazepoxide and 5-HT acted in a synergistic way, while such a synergy could not be obtained when chlordiazepoxide and GABA were coadministered. Moreover, the effects of intra-raphe chloridazepoxide no longer appeared in rats given intra dorsalis raphe 5-7 dihydroxytryptamine (3 micrograms in 0.4 microliters) 3 weeks before testing. All these results further support the hypothesis of the involvement of 5-HT neurons both in punishment-induced inhibition and in the antipunishment activity of benzodiazepines. No evidence was obtained suggesting a GABAergic mediation for the functional interaction of chlordiazepoxide with 5-HT neurons in this experimental model. Since high 3H-flunitrazepam binding was found at the raphe dorsalis level, and since a 30% decrease in the number of intra-raphe 3H-flunitrazepam binding sites was detected after intra-raphe 5-7 dihydroxytryptamine, it is possible that intra-raphe chlordiazepoxide controls 5-HT neurons partly through some benzodiazepine binding sites located on 5-HT cells.
D015116:5,7-Dihydroxytryptamine / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002707:Chlordiazepoxide / Q000494:pharmacology*; D003891:Desipramine / Q000494:pharmacology; D005445:Flunitrazepam / Q000378:metabolism; D008297:Male; D011678:Punishment; D011903:Raphe Nuclei / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000494:pharmacology*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D015116:5,7-Dihydroxytryptamine; D012701:Serotonin; D005680:gamma-Aminobutyric Acid; D005445:Flunitrazepam; D002707:Chlordiazepoxide; D003891:Desipramine