Sex-related differences in central adrenergic function and responsiveness to repeated administration of desipramine or electroconvulsive shock.
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.
Heal
D J
DJ
Research Department, Boots Company PLC, Nottingham.
Bristow
L M
LM
Hurst
E M
EM
Elliott
J M
JM
Buckett
W R
WR
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*
D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D003000:Clonidine; D003891:Desipramine