EFFECTS OF ALPHA-2-ADRENOCEPTOR AND BETA-ADRENOCEPTOR AGONISTS ON GROWTH-HORMONE SECRETION FOLLOWING LESION OF THE NORADRENERGIC SYSTEM OF THE RAT

The aim of the present investigation was to lesion the noradrenergic system and to measure the effect on growth hormone (GH) secretion following peripheral administration of alpha-2- and beta-adrenoceptor agonists. Direct injection of these agonists into the paraventricular nucleus of the hypothalamus (PVN) and its effect on GH secretion were also investigated. Systemic administration of N-2-chloroethyl-N-ethyl-2-bromobenzylamine (DSP4, 60 mg/kg, injected i.p. 10 days prior to experimentation) significantly decreased the noradrenaline (NA) content of the hippocampus, frontal cortex and hypothalamus but had no effect on the dopamine (DA) or serotonin (5-HT) content of these areas. Bilateral injection of 6-hydroxydopamine (6-OHDA, 10 mug/mul, 14 days prior to experimentation) into the medial forebrain bundle (MFB) caused a greater reduction of NA and also decreased the DA and 5-HT content of the hypothalamus. Analysis of the PVN of the hypothalami of rats following 6-OHDA lesion of the MFB showed significantly decreased NA and 5-HT content. Neither DSP4 treatment nor 6-OHDA lesion of the MFB affected the clonidine (250 mug/kg, i.p.) induced stimulation of GH secretion. Injection of isoproterenol (1 mg/kg, i.p.) had varying effects on GH secretion. It stimulated GH release in control rats but not in DSP4 or MFB lesioned rats. Direct injection of clonidine (0.1 mug/mul) into the PVN significantly stimulated GH secretion, whereas injection of isoproterenol (2.5 mug/mul) into the PVN did not affect GH levels when compared to controls. The results of the present study do not support the hypothesis that hypoactivity of the central noradrenergic system may be the cause of the blunted GH response to clonidine observed in depressed patients.