title: 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 alpha 2-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 alpha 2-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 alpha 2- and beta-adrenoceptors in rat cortex. Cortical alpha 2-adrenoceptors were decreased by 14 days of DMI injection or 10 days of ECS treatment (ECS x 10) and these effects were identical in both sexes. These receptors were not altered by 2 days administration of DMI or ECS. Cortical beta-adrenoceptors were reduced in male and female rats by 2 and 14 days of DMI injection and by ECS x 10, but not ECS x 2. 5. Viewed overall, the data show differences in alpha 2-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 alpha 2- and beta-adrenoceptor binding experiments using rat cortical tissue.
authors.affiliation: Research Department, Boots Company PLC, Nottingham.
authors.forename: D J
authors.initials: DJ
authors.lastname: Heal
authors.forename: L M
authors.initials: LM
authors.lastname: Bristow
authors.forename: E M
authors.initials: EM
authors.lastname: Hurst
authors.forename: J M
authors.initials: JM
authors.lastname: Elliott
authors.forename: W R
authors.initials: WR
authors.lastname: Buckett
mesh_terms: D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D003000:Clonidine / Q000494:pharmacology; D003891:Desipramine / Q000494:pharmacology*; D004597:Electroshock; D004971:Estrus / Q000187:drug effects; D005260:Female; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism; D011943:Receptors, Adrenergic, beta / Q000378:metabolism; D012737:Sex Factors; D013564:Sympathetic Nervous System / Q000502:physiology*
chemical_list: D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D003000:Clonidine; D003891:Desipramine