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 a2-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; 5mg 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 a2-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 a2-and ,B-adrenoceptors in rat cortex. Cortical a2-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 fi-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 a2-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 a2-and /-adrenoceptor binding experiments using rat cortical tissue.

Remote Limb Ischemic Preconditioning Attenuates Cerebrovascular Depression During Sinusoidal Galvanic Vestibular Stimulation via α 1 ‐Adrenoceptor–Protein Kinase Cε–Endothelial NO Synthase Pathway in Rats

“…observed a sustained increase in cerebral blood flow perfusion in mice subjected to RIPC that may be dependent on increased eNOS/nitric oxide/nitrite . Our findings also strengthen the downstream signaling of RIPC converging on the eNOS pathway and the critical role of eNOS in RIPC protection of cerebral blood flow …”

“…Interestingly, although female rats had less cardiovascular depression due to sGVS, the response to cerebrovascular depression was significantly greater than the vehicle‐PC male rats (ie, vehicle‐PC female rats had a greater drop in cerebral perfusion than vehicle‐PC male rats) (Figure C). Previous studies have reported little to no difference in the brain affinity of β‐adrenoceptors in rats, but the response of brain α 2 ‐adrenoceptors is different between the sexes . Additionally, there is still a debate on whether sex differences exist or not in regulation of cerebral blood flow, yet it seems more likely that there is a sex difference in response of the cerebral blood flow .…”

“…Previous studies have reported little to no difference in the brain affinity of b-adrenoceptors in rats, but the response of brain a 2 -adrenoceptors is different between the sexes. 25 Additionally, there is still a debate on whether sex differences exist or not in regulation of cerebral blood flow, 26 yet it seems more likely that there is a sex difference in response of the cerebral blood flow. 27 In either case, additional experiments are needed to better understand the observed differences in the cardio-and cerebrovascular responses between female and male rats.…”

Determination of the role of noradrenergic and 5‐hydroxytryptaminergic neurones in postsynaptic α2‐adrenoceptor desensitization by desipramine and ECS

“…mydriasis results from activation of x2-adrenoceptors in the Edinger-Westphal nucleus (Sharpe & Pickworth, 1981), whereas ligand-receptor binding is generally measured in the cortex. In agreement with the current findings, cortical a2-adrenoceptors have been reported to be decreased by repeated treatment with desipramine or ECS (Smith et al, 1981;Stanford & Nutt, 1982;Pilc & Vetulani, 1982;Heal et al, 1987;1989c). However, the former observation has been disputed by others (Johnson et al, 1980;Asakura et al, 1982;Sugrue, 1983;Stanford et al, 1983).…”

The experimental and clinical pharmacology of St John's Wort (Hypericum perforatum L.)

“…17 This finding is similar to binding studies, both in vivo and in vitro showing that chronic but not acute, treatment with antidepressants drugs and ECT downregulates ␤ 1 -adrenoceptors in rat forebrain. [29][30][31][32] Data from previous studies also suggest that adaptive changes in the 5-HT system may also play a pivotal role in the therapeutic effect of antidepressants. It has been shown that long-term TCA and repeated ECT lead to an enhanced 5-HT neurotransmission through a progressive sensitisation and upregulation of the postsynaptic 5-HT 1A receptors in the dorsal hippocampus.…”