The influence of injection of oestradiol to female rats on changes in α2- and β-adrenoceptor function induced by repeated administration of desipramine or electroconvulsive shock

Abstract Repeated daily administration to female rats of either an electroconvulsive shock (110 V, 1 sec) or desipramine (DMI; 5 mg/kg × 2) caused a progressive decrease in presynaptic α 2 -adrenoceptor function assessed by the hypoactivity (sedation) response to clonidine (0.5 mg/kg). This reduction was maximal after approximately seven electroshocks or 8–12 days of injection of DMI. Daily administration of oestradiol (100 μg s.c.), starting one day prior to the commencement of administration of DMI or treatment with electroshock, markedly accelerated the onset of decreased hypoactivity responses to clonidine, but did not alter the maximum reduction induced by repeated injection of DMI or administration of electroshock. Injection of oestradiol alone had no effect on the responses to clonidine. Administration of DMI for 14 days decreased the number of both α 2 - and β-adrenoceptors in the cortex. Cortical β-, but not α 2 -adrenoceptors, were also decreased after 4 days of injection of DMI. Two and ten electroshocks moderately increased and decreased cortical α 2 -adrenoceptors, respectively. β-Adrenoceptors were also decreased by ten electroshocks, but two were without effect. Simultaneous administration of oestradiol had little influence on the changes in the binding of α 2 - or β-adrenoceptors induced by repeated administration of DMI or treatment with electroshock. Oestradiol increased the numbers of cortical α 2 - and β-adrenoceptors 3 and 15 days after injection, respectively. The results, therefore, demonstrate a specific interaction between oestradiol and 2 treatments with antidepressants (DMI and electroshock) on hypoactivity responses induced by clonidine and these findings are discussed with reference to the suggested potentiation of the clinical efficacy of antidepressants by the administration of oestradiol.