Alpha2A and alpha2C-adrenoceptor regulation in the brain: alpha2A changes persist after chronic stress.
Stress-induced activation of the central nervous noradrenergic system has been suspected to induce depressive disorders. As episodes of depression often occur some time after a stress experience we investigated whether stress-induced changes in the alpha2-adrenoceptor (alpha2-AR) system persist throughout a post-stress recovery period. Brains of male tree shrews were analysed after 44 days of chronic psychosocial stress and after a subsequent 10-day recovery period. Expression of RNA for alpha2A and alpha2C-adrenoceptors was quantified by in situ hybridization, and receptor binding was determined by in vitro receptor autoradiography. Activities of the sympathetic nervous system and of the hypothalamo-pituitary-adrenal axis were increased during chronic stress but normalized during recovery. Alpha2A-AR RNA in the glutamatergic neurons of the lateral reticular nucleus was elevated significantly after stress and after recovery (by 29% and 17%). In the dorsal motor nucleus of the vagus, subtype A expression was enhanced after recovery (by 33%). In the locus coeruleus, subtype A autoreceptor expression was not changed significantly. Subtype C expression in the caudate nucleus and putamen was elevated by stress (by 5 and 4%, respectively) but normalized during recovery. Quantification of 3H-RX821002 binding revealed receptor upregulation during stress and/or recovery. Our data therefore show: (i) that chronic psychosocial stress differentially regulates expression of alpha2-adrenoceptor subtypes A and C; (ii) that subtype A heteroreceptor expression is persistently upregulated whereas (iii), subtype C upregulation is only transient. The present findings coincide with post mortem studies in depressed patients revealing upregulation of alpha2A-ARs.
Flügge
G
G
Department of Neurobiology, German Primate Centre, Kellnerweg 4, 37077 Göttingen, Germany. gfluegg@gwdg.de
van Kampen
M
M
Meyer
H
H
Fuchs
E
E
D000818:Animals; D001345:Autoradiography; D001483:Base Sequence; D001921:Brain / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology; D007030:Hypothalamo-Hypophyseal System / Q000502:physiology; D017403:In Situ Hybridization; D008297:Male; D008969:Molecular Sequence Data; D009474:Neurons / Q000378:metabolism; D010913:Pituitary-Adrenal System / Q000502:physiology; D012333:RNA, Messenger / Q000032:analysis; D018341:Receptors, Adrenergic, alpha-2 / Q000378:metabolism*; D013315:Stress, Psychological / Q000235:genetics / Q000503:physiopathology*; D013564:Sympathetic Nervous System / Q000502:physiology; D014418:Tupaiidae / Q000502:physiology*
D012333:RNA, Messenger; D018341:Receptors, Adrenergic, alpha-2