Drug discrimination and drug stimulus generalization with anxiolytics

Abstract

Work with lorazepam in two-lever food-maintained drug discrimination procedures with baboons and rats found greater specificity in the generalization profile when this drug was used as a training drug compared to studies with other benzodiazepines (BZ). That is, animals trained to discriminate lorazepam have not reliably made the drug response in tests with barbiturates, although animals trained to discriminate diazepam, chlordiazepoxide, triazolam, oxazepam, and sometimes midazolam commonly have done so. Characterization of the discriminative stimulus effects of lorazepam has included manipulation of species, training dose, and route of administration; drug interaction studies: and tests with a variety of anxiolytics. The time course of the discriminative stimulus effects of lorazepam and other drugs also has been studied using a multiple session procedure in baboons. Some of these results have provided information relevant to the extent to which intermediate levels of the drug response in test sessions at doses that do not reduce response rates may meaningfully reflect threshold or partial drug stimulus effects.

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

“…In studies with rats trained to discriminate midazolam, one reported generalization to pentobarbital (Garcha et al 1985) but a second from the same laboratory reported a maximum of 60% drug-appropriate responding in tests with pentobarbital (Rauch and Stolerman 1987). In recent work in our laboratory, pentobarbital occasioned drug lever responding in all rats trained to discriminate 0.32 or 1.0 mg/kg midazolam IP, with the pentobarbital generalization gradient shifted to the right for the group trained with the higher dose of midazolam (Ator 1989). The variables responsible for these differences in results across studies with midazolam remain to be determined.…”

Serotonergic/glutamatergic interactions: the effects of mGlu 2/3 receptor ligands in rats trained with LSD and PCP as discriminative stimuli

“…In contrast, the dose of LY379268 (3.0 mg/kg) that partially antagonized LSD-induced stimulus control also produced a significant decrease in the rate of responding. In studies of drug-induced stimulus control, the interpretation of intermediate results, whether intermediate generalization or antagonism, is problematical (Winter 1978;Ator 1990;Koek 1999). Nonetheless, the effects of LY379268 as seen in Fig.…”

Discriminative stimulus effects of ethanol and 3α-hydroxy-5α-pregnan-20-one in relation to menstrual cycle phase in cynomolgus monkeys ( Macaca fascicularis )

“…As noted in the introduction, both ethanol and allopregnanolone act as positive modulators of these receptor complexes in neurochemical and electrophysiological assays (Liedenheimer and Harris 1992;Hawkinson et al 1994). Furthermore, in drug discrimination procedures, there is a large degree of overlap between the discriminative stimulus effects of ethanol, the neuroactive steroids allopregnanolone and THDOC, and two other classes of GABA A receptor positive modulators, the benzodiazepines and barbiturates (Ator 1990;Ator et al 1993;Deutsch and Mastropaolo 1993). Although both ethanol and allopregnanolone can act to antagonize the cation conductance of the NMDA subtypes of glutamate receptors, allopregnanolone's effects are negligible at this receptor complex (Irwin et al 1994).…”