EFFECTS OF CHLORDIAZEPOXIDE AND PUTATIVE ANXIOGENICS ON CONDITIONED SUPPRESSION IN RATS

L TOAL, Julian Leslie, RA SHEPHARD

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

This paper reports two experiments. In Experiment 1, the effects of chlordiazepoxide alone and in combination with a series of putative antagonists at various sites on the GABA/benzodiazepine receptor complex on conditioned suppression of operant behavior in rats were assessed. Response rates during presentation of a stimulus associated with shock (CS responding) and when only positive reinforcement is effective (pre-CS responding) were analysed. Chlordiazepoxide (10 mg/kg) significantly increased CS responding. This effect was significantly antagonised by Ro15-1788 (10 mg/kg) and by picrotoxin (1.5 mg/kg), but not by bicuculline (1.5 mg/kg) or by delta-amino-n-valeric acid (10 or 20 mg/kg). Chlordiazepoxide also significantly, albeit more slightly, increased pre-CS responding and none of the other drugs tested significantly antagonised this action, though Ro15-1788 plus chlordiazepoxide resulted in pre-CS response rates not significantly different from either chlordiazepoxide alone or control. These interactions are discussed in the context of the proposed GABA/benzodiazepine receptor complex with the conclusion that drug effects at the benzodiazepine- and picrotoxin-sensitive channel sites have an important role in mediating anxiolytic action. However, behavioral evidence of an important role for GABAa or GABAb receptors remains very limited. The second experiment studied the intrinsic actions of bicuculline, picrotoxin, and Ro15-1788 on conditioned suppression. Responding during a conditioned stimulus associated with a mild (0.125 to 0.15 mA) electric shock (CS responding) and a control rate of responding (pre-CS responding) were recorded. Bicuculline (1.5 mg/kg) and Ro15-1788 (10 mg/kg) did not significantly affect either response rate. Picrotoxin (1.5 mg/kg) significantly reduced both response rates. These results are discussed in the context of drug interaction studies with these compounds and of animal paradigms for the detection of anxiogenic drug effects.
LanguageEnglish
Pages1085-1090
JournalPhysiology and Behavior
Volume49
Issue number6
Publication statusPublished - Jun 1991

Fingerprint

Chlordiazepoxide
Picrotoxin
Bicuculline
GABA-A Receptors
Shock
Pharmaceutical Preparations
Anti-Anxiety Agents
Benzodiazepines
Drug Interactions

Cite this

@article{657e0a3b7e994b75a425f681fa19b3ae,
title = "EFFECTS OF CHLORDIAZEPOXIDE AND PUTATIVE ANXIOGENICS ON CONDITIONED SUPPRESSION IN RATS",
abstract = "This paper reports two experiments. In Experiment 1, the effects of chlordiazepoxide alone and in combination with a series of putative antagonists at various sites on the GABA/benzodiazepine receptor complex on conditioned suppression of operant behavior in rats were assessed. Response rates during presentation of a stimulus associated with shock (CS responding) and when only positive reinforcement is effective (pre-CS responding) were analysed. Chlordiazepoxide (10 mg/kg) significantly increased CS responding. This effect was significantly antagonised by Ro15-1788 (10 mg/kg) and by picrotoxin (1.5 mg/kg), but not by bicuculline (1.5 mg/kg) or by delta-amino-n-valeric acid (10 or 20 mg/kg). Chlordiazepoxide also significantly, albeit more slightly, increased pre-CS responding and none of the other drugs tested significantly antagonised this action, though Ro15-1788 plus chlordiazepoxide resulted in pre-CS response rates not significantly different from either chlordiazepoxide alone or control. These interactions are discussed in the context of the proposed GABA/benzodiazepine receptor complex with the conclusion that drug effects at the benzodiazepine- and picrotoxin-sensitive channel sites have an important role in mediating anxiolytic action. However, behavioral evidence of an important role for GABAa or GABAb receptors remains very limited. The second experiment studied the intrinsic actions of bicuculline, picrotoxin, and Ro15-1788 on conditioned suppression. Responding during a conditioned stimulus associated with a mild (0.125 to 0.15 mA) electric shock (CS responding) and a control rate of responding (pre-CS responding) were recorded. Bicuculline (1.5 mg/kg) and Ro15-1788 (10 mg/kg) did not significantly affect either response rate. Picrotoxin (1.5 mg/kg) significantly reduced both response rates. These results are discussed in the context of drug interaction studies with these compounds and of animal paradigms for the detection of anxiogenic drug effects.",
author = "L TOAL and Julian Leslie and RA SHEPHARD",
year = "1991",
month = "6",
language = "English",
volume = "49",
pages = "1085--1090",
journal = "Physiology and Behavior",
issn = "0031-9384",
publisher = "Elsevier Inc.",
number = "6",

}

EFFECTS OF CHLORDIAZEPOXIDE AND PUTATIVE ANXIOGENICS ON CONDITIONED SUPPRESSION IN RATS. / TOAL, L; Leslie, Julian; SHEPHARD, RA.

In: Physiology and Behavior, Vol. 49, No. 6, 06.1991, p. 1085-1090.

Research output: Contribution to journalArticle

TY - JOUR

T1 - EFFECTS OF CHLORDIAZEPOXIDE AND PUTATIVE ANXIOGENICS ON CONDITIONED SUPPRESSION IN RATS

AU - TOAL, L

AU - Leslie, Julian

AU - SHEPHARD, RA

PY - 1991/6

Y1 - 1991/6

N2 - This paper reports two experiments. In Experiment 1, the effects of chlordiazepoxide alone and in combination with a series of putative antagonists at various sites on the GABA/benzodiazepine receptor complex on conditioned suppression of operant behavior in rats were assessed. Response rates during presentation of a stimulus associated with shock (CS responding) and when only positive reinforcement is effective (pre-CS responding) were analysed. Chlordiazepoxide (10 mg/kg) significantly increased CS responding. This effect was significantly antagonised by Ro15-1788 (10 mg/kg) and by picrotoxin (1.5 mg/kg), but not by bicuculline (1.5 mg/kg) or by delta-amino-n-valeric acid (10 or 20 mg/kg). Chlordiazepoxide also significantly, albeit more slightly, increased pre-CS responding and none of the other drugs tested significantly antagonised this action, though Ro15-1788 plus chlordiazepoxide resulted in pre-CS response rates not significantly different from either chlordiazepoxide alone or control. These interactions are discussed in the context of the proposed GABA/benzodiazepine receptor complex with the conclusion that drug effects at the benzodiazepine- and picrotoxin-sensitive channel sites have an important role in mediating anxiolytic action. However, behavioral evidence of an important role for GABAa or GABAb receptors remains very limited. The second experiment studied the intrinsic actions of bicuculline, picrotoxin, and Ro15-1788 on conditioned suppression. Responding during a conditioned stimulus associated with a mild (0.125 to 0.15 mA) electric shock (CS responding) and a control rate of responding (pre-CS responding) were recorded. Bicuculline (1.5 mg/kg) and Ro15-1788 (10 mg/kg) did not significantly affect either response rate. Picrotoxin (1.5 mg/kg) significantly reduced both response rates. These results are discussed in the context of drug interaction studies with these compounds and of animal paradigms for the detection of anxiogenic drug effects.

AB - This paper reports two experiments. In Experiment 1, the effects of chlordiazepoxide alone and in combination with a series of putative antagonists at various sites on the GABA/benzodiazepine receptor complex on conditioned suppression of operant behavior in rats were assessed. Response rates during presentation of a stimulus associated with shock (CS responding) and when only positive reinforcement is effective (pre-CS responding) were analysed. Chlordiazepoxide (10 mg/kg) significantly increased CS responding. This effect was significantly antagonised by Ro15-1788 (10 mg/kg) and by picrotoxin (1.5 mg/kg), but not by bicuculline (1.5 mg/kg) or by delta-amino-n-valeric acid (10 or 20 mg/kg). Chlordiazepoxide also significantly, albeit more slightly, increased pre-CS responding and none of the other drugs tested significantly antagonised this action, though Ro15-1788 plus chlordiazepoxide resulted in pre-CS response rates not significantly different from either chlordiazepoxide alone or control. These interactions are discussed in the context of the proposed GABA/benzodiazepine receptor complex with the conclusion that drug effects at the benzodiazepine- and picrotoxin-sensitive channel sites have an important role in mediating anxiolytic action. However, behavioral evidence of an important role for GABAa or GABAb receptors remains very limited. The second experiment studied the intrinsic actions of bicuculline, picrotoxin, and Ro15-1788 on conditioned suppression. Responding during a conditioned stimulus associated with a mild (0.125 to 0.15 mA) electric shock (CS responding) and a control rate of responding (pre-CS responding) were recorded. Bicuculline (1.5 mg/kg) and Ro15-1788 (10 mg/kg) did not significantly affect either response rate. Picrotoxin (1.5 mg/kg) significantly reduced both response rates. These results are discussed in the context of drug interaction studies with these compounds and of animal paradigms for the detection of anxiogenic drug effects.

M3 - Article

VL - 49

SP - 1085

EP - 1090

JO - Physiology and Behavior

T2 - Physiology and Behavior

JF - Physiology and Behavior

SN - 0031-9384

IS - 6

ER -