Hypothermia induced by baclofen, a possible index of GABAB receptor function in mice, is enhanced by antidepressant drugs and ECS.
1 Intraperitoneal injection to mice of the gamma-aminobutyric acidB (GABAB) 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 GABAB 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 GABAB receptor function in the brain and strengthens the evidence that GABAB receptor function is enhanced by antidepressant drugs and ECS.
Gray
J A
JA
MRC Clinical Pharmacology Unit, Radcliffe Infirmary, Oxford.
Goodwin
G M
GM
Heal
D J
DJ
Green
A R
AR
D015116:5,7-Dihydroxytryptamine / Q000494:pharmacology; D000639:Amitriptyline / Q000494:pharmacology; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001418:Baclofen / Q000008:administration & dosage / Q000494:pharmacology*; D001831:Body Temperature / Q000187:drug effects*; D004597:Electroshock; D005479:Flurazepam / Q000494:pharmacology; D006993:Hypnotics and Sedatives; D007274:Injections, Intraperitoneal; D007276:Injections, Intraventricular; D008297:Male; D051379:Mice; D009434:Neural Pathways / Q000187:drug effects; D010424:Pentobarbital / Q000494:pharmacology; D011963:Receptors, GABA-A / Q000187:drug effects*
D000928:Antidepressive Agents; D006993:Hypnotics and Sedatives; D011963:Receptors, GABA-A; D000639:Amitriptyline; D015116:5,7-Dihydroxytryptamine; D001418:Baclofen; D010424:Pentobarbital; D005479:Flurazepam