Sex-related differences in central adrenergic function and responsiveness to repeated administration of desipramine or electroconvulsive shock

Abstract

1 Clonidine induces hypoactivity in rodents. Male rats were found to be markedly more susceptible to the sedative effects of this α₂-adrenoceptor agonist than females. Thus to obtain identical hypoactivity responses for subsequent experiments, clonidine was administered to male and female rats at doses of 0.2 and 0.5 mg kg⁻¹, respectively. 2 The clonidine-induced hypoactivity response of female rats was not affected by the oestrous cycle. 3 Repeated injection of desipramine (DMI; 5 mg kg⁻¹ b.d.) for up to 14 days progressively attenuated clonidine-induced hypoactivity in both male and female rats. However, in males the attenuation was more rapid in onset and a greater overall reduction was obtained. This α₂-adrenoceptor-mediated response was also progressively reversed by repeated daily administration of an electroconvulsive shock (ECS; 110 V, 1 s). In this case, although the maximum decrease was greater in males, the time of onset was identical in both sexes. 4 There were no sex-related differences in either the number or affinity of α₂- and β-adrenoceptors in rat cortex. Cortical α₂-adrenoceptors were decreased by 14 days of DMI injection or 10 days of ECS treatment (ECS × 10) and these effects were identical in both sexes. These receptors were not altered by 2 days administration of DMI or ECS. Cortical β-adrenoceptors were reduced in male and female rats by 2 and 14 days of DMI injection and by ECS × 10, but not ECS × 2. 5 Viewed overall, the data show differences in α₂-adrenoceptor function between the sexes, as determined by clonidine-induced hypoactivity and the responsiveness of this paradigm to repeated administration of DMI and ECS. In contrast, no differences were observed in complementary α₂- and β-adrenoceptor binding experiments using rat cortical tissue.