title: Are the effects of benzodiazepines on discrimination and punishment dissociable?
abstract: Studies have shown that benzodiazepines (BZs) both disrupt discrimination and increase resistance to punishment. Using a delayed response task, we provide evidence that effects of BZs on discrimination cannot be fully explained by deficits in either short or long term memory, or by intolerance for delay of reward. A schedule with rewarded, nonrewarded (Time out: TO) and conflict components was used to investigate effects in rats of compounds active at the BZ receptor on successive discrimination and punished responding in parallel. The GABA transaminase inhibitor ethanolamine-O-sulphate exerted additive effects with chlordiazepoxide (CDP) on punished but not TO responding. Both GABA and CDP injected into the amygdala selectively increased conflict rates, but with peripheral treatment CDP also increased TO rates. Two inverse BZ agonists, CGS 8216 and FG 7142 antagonzied the anti-conflict effects of GABA and CDP, given within the amygdala or peripherally, but the increase in TO rates induced by systemic CDP was counteracted only by peripheral treatments. These compounds also reduced rates of conflict responding below baseline, consistent with anxiogenic activity. Effects of the BZ antagonist Ro 15-1788 were broadly similar to those of the inverse agonists, except that it did not antagonise the anti-conflict action of intra-amygdaloid GABA, nor significantly reduce punished responding at the single dose used. We conclude from these results that the anti-conflict effects of BZs are mediated by a GABAergic amygdaloid mechanism, but that the same mechanism is not involved in BZ effects on discrimination.
authors.affiliation: Department of Psychology, Institute of Psychiatry, London.
authors.forename: H
authors.initials: H
authors.lastname: Hodges
authors.forename: S
authors.initials: S
authors.lastname: Green
mesh_terms: D000679:Amygdala / Q000187:drug effects; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001569:Benzodiazepines / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D002243:Carbolines / Q000494:pharmacology; D002707:Chlordiazepoxide / Q000494:pharmacology; D004192:Discrimination, Psychological / Q000187:drug effects*; D004983:Ethanolamines / Q000494:pharmacology; D005442:Flumazenil / Q000494:pharmacology; D008874:Midazolam / Q000494:pharmacology; D011678:Punishment; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D011963:Receptors, GABA-A / Q000187:drug effects*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
chemical_list: D002243:Carbolines; D004983:Ethanolamines; D011720:Pyrazoles; D011963:Receptors, GABA-A; D001569:Benzodiazepines; D005442:Flumazenil; D005680:gamma-Aminobutyric Acid; C035874:FG 7142; D002707:Chlordiazepoxide; C033830:2-phenylpyrazolo(4,3-c)quinolin-3(5H)-one; C020619:ethanolamine O-sulfate; D008874:Midazolam