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Hypothermia induced by baclofen, a possible index of GABA B receptor function in mice, is enhanced by antidepressant drugs and ECS
Author(s) -
Gray Julian A.,
Goodwin Guy M.,
Heal David J.,
Green A. Richard
Publication year - 1987
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1987.tb11392.x
Subject(s) - baclofen , pharmacology , desipramine , hypothermia , gabab receptor , agonist , medicine , muscle relaxant , antidepressant , anesthesia , sedation , receptor , endocrinology , hippocampus
1 Intraperitoneal injection to mice of the γ‐aminobutyric acid B (GABA B ) receptor agonist (±)‐baclofen induces a dose‐dependent decrease in rectal temperature. 2 Injection of (–)‐baclofen intracerebroventricularly at doses that had no effect when given peripherally induced a marked hypothermia. (+)‐Baclofen was without effect. 3 The decrease in rectal temperature induced by (–)‐baclofen when injected intraperitoneally was highly correlated with an increase in sedation. 4 Repeated administration of amitriptyline (10 mg kg −1 daily for 14 days) resulted in mice displaying an enhanced temperature and sedation response to injection of (±)‐baclofen (5 mg kg −1 ) 24 h after the last dose of antidepressant. 5 An enhanced hypothermic response was also seen following repeated administration of zimeldine, mianserin or desipramine (all 10 mg kg −1 daily for 14 days) or repeated electroconvulsive shock (ECS; 5 ECS over 10 days) 24 h after the last treatment. 6 A single administration of any of the antidepressant drugs or ECS or repeated administration of the anxiolytic drug flurazepam (20 mg kg −1 daily for 14 days) did not alter the baclofen‐induced hypothermic response. 7 Administration of (±)‐baclofen (5 mg kg −1 ) daily for 5 or 14 days attenuated the baclofen‐induced hypothermic response. However, one pretreatment dose did not alter the response. 8 It has previously been reported that repeated baclofen administration decreases GABA B receptor number in the brain while repeated administration of antidepressant drugs and ECS increases the density of this receptor. The current data therefore suggest that baclofen‐induced hypothermia may provide a simple index of GABA B receptor function in the brain and strengthens the evidence that GABA B receptor function is enhanced by antidepressant drugs and ECS.