Imidazoline₂ (I₂) receptor- and α ₂-adrenoceptor-mediated modulation of hypothalamic-pituitary-adrenal axis activity in control and acute restraint stressed rats

Central noradrenaline regulates the activity of the hypothalamic-pituitary-adrenal (HPA) axis and the neuroendocrine response to stress. α₂-adrenoceptors and imidazoline₂ (I ₂) receptors modulate the activity of the central noradrenergic system. The present set of experiments investigated the role of α ₂-adrenoceptors and I₂ receptors in the regulation of HPA axis activity under basal conditions and during exposure to the acute psychological stress of restraint. Three separate experiments were carried out in which rats were given an i.p. injection of either saline vehicle, the combined α₂-adrenoceptor antagonist and 12 receptor ligand idazoxan (10 mg/kg), the selective I₂ receptor ligand BU224 (2.5 or 10 mg/kg) or the selective α₂-adrenoceptor antagonist RX821002 (2.5 mg/kg) with or without restraint stress. Drugs were administered immediately prior to restraint of 60 min duration. Blood was sampled pre-injection, 30, 60 and 240 min post-injection and plasma corticosterone was measured by radioimmunoassay. In experiment 1, idazoxan increased plasma corticosterone levels in naive animals and potentiated the corticosterone response to acute restraint stress. In experiment 2, BU224 administration increased plasma corticosterone levels in a dose-related manner in naive rats. The results of experiment 3 indicated that RX821002 also elevated plasma corticosterone levels in naive rats, however, only BU224 potentiated the corticosterone response to restraint stress. These studies suggest that both α₂-adrenoceptors and 12 receptors play a role in modulating basal HPA axis activity and that I₂ receptors may play a more important rote than α₂-adrenoceptors in modulating the HPA axis response to the acute psychological stress of restraint.