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Selectivity in the generalization profile in baboons trained to discriminate lorazepam: benzodiazepines, barbiturates and other sedative/anxiolytics.
J Pharmacol Exp Ther. 1997 Sep; 282(3):1442-57.JP

Abstract

The discriminative stimulus effects of benzodiazepines often have been indistinguishable from those of barbiturates or other sedative/anxiolytics. However, baboons and rats trained to discriminate lorazepam did not reliably generalize to pentobarbital in previous studies, although animals comparably trained to discriminate pentobarbital reliably generalized to lorazepam. The present study investigated the generalization profile for a variety of anxiolytic, sedative and other drugs in baboons trained to discriminate oral lorazepam (1.8 mg/kg). Triazolam, alprazolam, diazepam, midazolam, bromazepam, temazepam and nordiazepam occasioned >80% of total responses on the lorazepam-paired lever, in that order of potency, 60 min after oral dosing; chlordiazepoxide did so in three of five baboons. However, barbiturates (amobarbital, hexobarbital, methohexital, pentobarbital, phenobarbital, secobarbital) and methypryIon occasioned lorazepam-appropriate responding in only one or two baboons. Testing barbiturates at different pretreatment times (amobarbital, hexobarbital, pentobarbital or secobarbital) or by an i.m. route of administration (methohexital, pentobarbital) did not produce an increase in generalization. Neither other classic sedatives/anxiolytics (chloral hydrate, clomethiazole, ethanol, methaqualone, meprobamate, triclofos), nor anticonvulsants (phenytoin, valproic acid), nor drugs from other pharmacological classes shared discriminative-stimulus effects with lorazepam. These results, together with those from previous studies in which lorazepam or another benzodiazepine served as the training stimulus, indicate that lorazepam training results in a more selective generalization profile with respect to sedative/anxiolytic drugs than does training with other benzodiazepines.

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Publisher Full Text

Authors+Show Affiliations

Ator NA
Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, Maryland, USA.
Griffiths RR
No affiliation info available

MeSH

AnimalsAnti-Anxiety AgentsChloral HydrateChlormethiazoleDiscrimination LearningDose-Response Relationship, DrugGeneralization, PsychologicalHypnotics and SedativesLorazepamMaleMeprobamatePapio

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

9316858

Citation

Ator, N A., and R R. Griffiths. "Selectivity in the Generalization Profile in Baboons Trained to Discriminate Lorazepam: Benzodiazepines, Barbiturates and Other Sedative/anxiolytics." The Journal of Pharmacology and Experimental Therapeutics, vol. 282, no. 3, 1997, pp. 1442-57.
Ator NA, Griffiths RR. Selectivity in the generalization profile in baboons trained to discriminate lorazepam: benzodiazepines, barbiturates and other sedative/anxiolytics. J Pharmacol Exp Ther. 1997;282(3):1442-57.
Ator, N. A., & Griffiths, R. R. (1997). Selectivity in the generalization profile in baboons trained to discriminate lorazepam: benzodiazepines, barbiturates and other sedative/anxiolytics. The Journal of Pharmacology and Experimental Therapeutics, 282(3), 1442-57.
Ator NA, Griffiths RR. Selectivity in the Generalization Profile in Baboons Trained to Discriminate Lorazepam: Benzodiazepines, Barbiturates and Other Sedative/anxiolytics. J Pharmacol Exp Ther. 1997;282(3):1442-57. PubMed PMID: 9316858.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Selectivity in the generalization profile in baboons trained to discriminate lorazepam: benzodiazepines, barbiturates and other sedative/anxiolytics. AU - Ator,N A, AU - Griffiths,R R, PY - 1997/10/8/pubmed PY - 1997/10/8/medline PY - 1997/10/8/entrez SP - 1442 EP - 57 JF - The Journal of pharmacology and experimental therapeutics JO - J Pharmacol Exp Ther VL - 282 IS - 3 N2 - The discriminative stimulus effects of benzodiazepines often have been indistinguishable from those of barbiturates or other sedative/anxiolytics. However, baboons and rats trained to discriminate lorazepam did not reliably generalize to pentobarbital in previous studies, although animals comparably trained to discriminate pentobarbital reliably generalized to lorazepam. The present study investigated the generalization profile for a variety of anxiolytic, sedative and other drugs in baboons trained to discriminate oral lorazepam (1.8 mg/kg). Triazolam, alprazolam, diazepam, midazolam, bromazepam, temazepam and nordiazepam occasioned >80% of total responses on the lorazepam-paired lever, in that order of potency, 60 min after oral dosing; chlordiazepoxide did so in three of five baboons. However, barbiturates (amobarbital, hexobarbital, methohexital, pentobarbital, phenobarbital, secobarbital) and methypryIon occasioned lorazepam-appropriate responding in only one or two baboons. Testing barbiturates at different pretreatment times (amobarbital, hexobarbital, pentobarbital or secobarbital) or by an i.m. route of administration (methohexital, pentobarbital) did not produce an increase in generalization. Neither other classic sedatives/anxiolytics (chloral hydrate, clomethiazole, ethanol, methaqualone, meprobamate, triclofos), nor anticonvulsants (phenytoin, valproic acid), nor drugs from other pharmacological classes shared discriminative-stimulus effects with lorazepam. These results, together with those from previous studies in which lorazepam or another benzodiazepine served as the training stimulus, indicate that lorazepam training results in a more selective generalization profile with respect to sedative/anxiolytic drugs than does training with other benzodiazepines. SN - 0022-3565 UR - https://www.unboundmedicine.com/medline/citation/9316858/Selectivity_in_the_generalization_profile_in_baboons_trained_to_discriminate_lorazepam:_benzodiazepines_barbiturates_and_other_sedative/anxiolytics_ L2 - https://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=9316858 DB - PRIME DP - Unbound Medicine ER -