Benzodiazepine receptor ligand influences on acquisition: Suggestion of an endogenous modulatory mechanism mediated by benzodiazepine receptors

doi:10.1016/0163-1047(90)91221-V

Behavioral and Neural Biology

Volume 54, Issue 1, July 1990, Pages 27-41

https://doi.org/10.1016/0163-1047(90)91221-V Get rights and content

In rats, pretraining ip administration of the central benzodiazepine receptor antagonist, flumazenil (5.0 mg/kg), or of the inverse agonist, n-butyl-β-carboline-3-carboxylate (BCCB) (0.2 or 0.5 mg/kg), facilitated retention of a step-down inhibitory avoidance task; the central agonists, clonazepam and diazepam (0.4 or 1.0 mg/kg), had an opposite effect, and the peripheral agonist, 4′-chlordiazepam (1.25 or 6.25 mg/kg), was without effect. Pre- but not post-training flumazenil (2.0 mg/kg) blocked the effect of BCCB (0.5 mg/kg), clonazepam (1.0 mg/kg), or diazepam (1.0 mg/kg) given also pretraining. The post-training administration of all of these drugs had no effect on retention of the avoidance task. Flumazenil (5.0 mg/kg) and BCCB (0.5 mg/kg), given before training, enhanced retention test performance of habituation to a buzzer but not of habituation to an open field. In the three tasks studied, none of the drugs used had any appreciable effect on training session parameters. These results suggest that there is an endogenous mechanism mediated by benzodiazepine agonists, sensitive to inverse agonists, that normally down-regulates acquisition of certain behaviors; this mechanism becomes activated only when the tasks involve or occur with a certain degree of stress or anxiety (i.e., inhibitory avoidance or habituation to the buzzer) and not in less stressful or anxiogenic tasks (i.e., habituation to an open field).

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¹: Supported by a grant from FINEP, Brazil, to I.I. (No. 4.2.88.0273.00) and by a grant from CONICET, Argentina, to J.H.M. We thank Chen I. Huang for her technical assistance and Drs. Claudia Wolfman and Maria Beatriz C. Ferreira for valuable discussions.

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Benzodiazepine receptor ligand influences on acquisition: Suggestion of an endogenous modulatory mechanism mediated by benzodiazepine receptors

Neurochemistry International

Brain Research

Behavioral & Neural Biology

Behavioral Brain Research

Behavioral & Neural Biology

Behavioral & Neural Biology

Biochemical and Biophysical Research Communications

Psychoneuroendocrinology

Pharmacology, Biochemistry & Behavior

Life Sciences

Neuroscience and Biobehavioral Reviews

Trends in Neurosciences

Cholinergic mechanisms and aversively motivated behaviors

Urinary and brain β-carboline-3-carboxylates as potent inhibitors of brain benzodiazepine receptors

Posttraining administration of GABAergic antagonists enhances retention of aversively-motivated tasks

Psychopharmacology

Retrograde memory enhancement by diazepam: Its relation to anterograde amnesia, and some clinical implications

Psychopharmacology