Chronic desipramine treatment prevents the upregulation of cortical beta-receptors caused by a single dose of the benzodiazepine inverse agonist FG7142.
The beta-carboline FG7142 is a partial inverse agonist at benzodiazepine receptors. We have shown previously that a single dose of this drug causes an upregulation of cortical beta-adrenoceptor numbers in mouse cerebral cortex. This rise was seen seven days, but not 15-30 min or 24 h after FG7142 administration. We now report that two weeks pretreatment with the tricyclic antidepressant desipramine prevented the beta-adrenoceptor upregulation after a single dose of FG7142, although desipramine alone did not alter beta-adrenoceptor number. We also studied the effects of desipramine pretreatment on other pharmacological effects of FG7142 to see which of these effects might be related to the beta-adrenoceptor changes. Desipramine pretreatment caused a small, but significant, decrease in the depression of locomotor activity, but no change in the hypothermic action of FG7142. The possibility that upregulation of beta-adrenoceptors by FG7142 may be related to the behavioural actions of this compound is discussed.
Stanford
S C
SC
Department of Pharmacology, Middlesex Hospital Medical School, London, U.K.
Taylor
S C
SC
Little
H J
HJ
D000818:Animals; D001067:Appetite Depressants / Q000494:pharmacology*; D001831:Body Temperature / Q000187:drug effects; D002243:Carbolines / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D003216:Conditioning, Operant / Q000187:drug effects; D003891:Desipramine / Q000494:pharmacology*; D004082:Dihydroalprenolol; D008297:Male; D051379:Mice; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000378:metabolism*; D012055:Reinforcement Schedule
D001067:Appetite Depressants; D002243:Carbolines; D011943:Receptors, Adrenergic, beta; D004082:Dihydroalprenolol; C035874:FG 7142; D003891:Desipramine