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A simple model for studying benzodiazepines: Potentiation of hyperactivity induced by cocaine in mice
Author(s) -
Thiébot MarieHéléne,
Kloczko Joseph,
Chermat Raymond,
Soubrié Philippe,
Puech Alain J.,
Simon Pierre
Publication year - 1982
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/ddr.430010718
Subject(s) - chlordiazepoxide , nitrazepam , chemistry , flurazepam , pharmacology , picrotoxin , diazepam , prazosin , propranolol , benzodiazepine , bicuculline , oxazepam , gabaa receptor , clonazepam , endocrinology , antagonist , receptor , medicine , biochemistry
In mice tested for 60 min in photometer‐activity boxes, an increased locomotor activity (+50% to +100%) was observed after administration of cocaine (4 mg/kg i.p.). Such hyperactivity was markedly enhanced by all benzodiazepines studied (flurazepam excepted), at doses which did not modify spontaneous motility: chlordiazepoxide (1 mg/kg), diazepam (1 to 2 mg/kg), clobazam (1 mg/kg), oxazepam (0.25 mg/kg), nitrazepam (0.03 to 0.25 mg/kg), flunitrazepam (0.015 mg/kg), clonazepam (0.004 mg/kg) and lorazepam (0.004 mg/kg). These doses are very low, e.g., 8 to 20 times lower than those required to antagonize the locomotor stimulation caused by cocaine. The increase of cocaine‐induced hypermotility elicited by nitrazepam (0.125 mg/kg i.p.) was reduced or suppressed by impairing gamma‐aminobutyric acid (GABA)‐ergic transmission with picrotoxin (0.25 mg/kg) or by blocking α or β adrenergic receptors with prazosin (1 mg/kg i.p.) or propranolol (4 mg/kg i.p.), respectively. At these doses neither picrotoxin, prazosin, nor propranolol modified the spontaneous locomotor activity or the hyperactivity induced by cocaine alone. These results suggest that benzodiazepines may exert their facilitatory activity on cocaine‐induced hyperactivity by interfering with some central catecholaminergic processes either directly or through the involvement of a GABA‐ergic link.