Chronic desipramine treatment prevents the upregulation of cortical β-receptors caused by a single dose of the benzodiazepine inverse agonist FG7142

Abstract

The β-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 β-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 β-adrenoceptor upregulation after a single dose of FG7142, although desipramine alone did not alter β-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 β-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 β-adrenoceptors by FG7142 may be related to the behavioural actions of this compound is discussed.