Differential generalization to pentobarbital in rats trained to discriminate lorazepam, chlordiazepoxide, diazepam, or triazolam

Abstract

In drug discrimination studies benzodiazepine-trained animals have typically responded on the drug lever when tested with barbiturates. In a recent study, greater specificity appeared to be shown when lorazepam was used as a training drug. The generality and limits of this finding were explored in the present set of experiments. The asymmetrical cross-generalization found in lorazepam- and pentobarbital-trained baboons was replicated in rats and was shown not to be a function of either lorazepam (0.1., 0.32, or 1.0 mg/kg) or pentobarbital (10 or 25 mg/kg) training dose (i.e., pentobarbital-trained rats responded on the drug lever in tests with lorazepam, but lorazepam-trained rats did not show comparable pentobarbital generalization). In the next experiment, groups of rats were trained to discriminate chlordiazepoxide (10 mg/kg), triazolam (0.1 mg/kg), or diazepam (1.0 mg/kg). Generalization to both lorazepam and pentobarbital was shown by these rats. Finally after daily pentobarbital administration, lorazepam-trained rats made a sufficient number of responses after high pentobarbital doses to permit extension of the range of pentobarbital doses tested. Pentobarbital generalization increased, but still did not occur in all rats and was unreliable in successive tests in the same rats. These results suggest less homogeneity in the discriminative stimulus effects of "depressant drugs" than generally has been recognized.

Carisoprodol-Mediated Modulation of GABAA Receptors: In Vitro and in Vivo Studies

“…Although subjects trained to discriminate barbiturates do not generally distinguish between benzodiazepines and barbiturates in substitution studies (De Vry and Slangen, 1986;Ator and Griffiths, 1989;Woolverton and Nader, 1995), antagonists relatively selective for these sites will selectively block the discriminative stimulus effects of test compounds. That is, bemegride, a barbiturate antagonist, blocks the discriminative stimulus effects of pentobarbital but not benzodiazepines, whereas flumazenil, a benzodiazepine site antagonist, blocks the discriminative stimulus effects of benzodiazepines but not pentobarbital (Herling and Shannon, 1982;Schechter, 1984;De Vry and Slangen, 1986).…”

Drug Discrimination: Stimulus Control During Repeated Testing in Extinction

“…Lorazepam and no-drug training sessions always alternated, except as described below. No-drug training sessions were conducted without being preceded by vehicle injections, because the injection procedure does not appear to serve as a basis for drug/no-drug discrimination under a two-lever procedure in rats (Ator & Griffiths, 1989, 1999Overton, 1979).…”

The Discriminative Stimulus Effects of γ-Hydroxybutyrate and Related Compounds in Rats Discriminating Baclofen or Diazepam: The Role of GABAB and GABAA Receptors

“…and vehicle while responding under a FR10 schedule of food presentation in sessions comprising a 15-min timeout and 15-min response period. The dose of 1.0 mg/kg diazepam was chosen for training because this dose occasioned substantial drug lever-responding in rats discriminating 200 mg/kg GHB from vehicle (Carter et al, 2003) and has been studied extensively in rats (e.g., Ator and Griffiths, 1989).…”

“…Drug discrimination has been used extensively to investigate mechanisms of action partly because it has a high degree of pharmacologic specificity (Colpaert, 1978;Ator and Griffiths, 1989;Mansbach and Balster, 1991); i.e., drugs with similar discriminative stimulus effects typically share a mechanism of action. GHB can be discriminated by rats (Winter, 1981;Colombo et al, 1998;Metcalf et al, 2001;Carter et al, 2003) and pigeons (Koek et al, 2004), and previous studies have implicated both GABA A and GABA B receptors in the discriminative stimulus effects of GHB.…”