Research article

Alpha-2 adrenergic-induced changes in rectal temperature in adult and 13-day old rats following acute and repeated desipramine administration

Jean D Deupree¹ , William J Burke² and David B Bylund¹

¹  Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, 985800 Nebraska Medical Center, Omaha, NE 68198-5800 USA

²  Department of Psychiatry, University of Nebraska Medical Center, 985580 Nebraska Medical Center, Omaha, NE 68198-5580 USA

author email corresponding author email

BMC Pharmacology 2008, 8:17doi:10.1186/1471-2210-8-17

Published:	2 October 2008

Abstract

Background

The effects of acute and repeated treatment with desipramine on the functional response of α₂-adrenoceptors were tested in adult and 13-day old rats. The functional response measured was hypothermia that was induced by brimonidine, an α₂-adrenoceptor agonist. The change in the extent of the brimonidine-induced hypothermia following pretreatment with either single or 4 twice-daily injections of desipramine was compared in 13-day old and adult (65–75 days old) male rats.

Results

Brimonidine, alone, lowered rectal temperature to a greater extent in juvenile than in adult rats, and this response was dose-dependently blocked by the selective α₂-adrenoceptor antagonist, RX821002, in both groups of rats. Single desipramine administration lowered rectal temperature in the absence of brimonidine in adult but not in juvenile rats. The adult rats developed tolerance to this hypothermic effect after 4 days of desipramine treatment (10 mg/kg twice daily). Repeated desipramine treatment of adult rats also resulted in an enhancement in the brimonidine-induced hypothermic effect 24 h after the last dose, a time when above 90% of desipramine and its metabolite, desmethyldesipramine, had cleared the brain, but not at 14, 48 or 96 h after the last dose. In juvenile rats repeated injections of desipramine (3 mg/kg twice daily for 4 days) had no effect on the α₂-agonist-induced hypothermia when brimonidine was given 14, 24, 63 and 96 h after the last dose of desipramine.

Conclusion

The results suggest that juvenile rats response differently than adult rats to agonist stimulation of α₂-adrenoceptors with and without pretreatment with the antidepressant desipramine. In the absence of desipramine pretreatment, the α₂-adrenoceptor-induced hypothermic effect in juvenile rats is greater than in adult rats. Acute injections of desipramine, in the absence of agonist produced a hypothermic effect in adult but not juvenile rats. In addition, the increased α₂-agonist-induced hypothermic effect following repeated injections of desipramine that is seen in adult rats is not seen in juvenile rats.