title: Alterations in sensitivity to intracerebral vasopressin and the effects of a V1a receptor antagonist on cellular, autonomic and endocrine responses to repeated stress.
abstract: We have shown previously that repeated restraint stress results in differential adaptation at both macrophysiological and cellular levels. Chronic stress accentuates vasopressinergic control of adrenocorticotropic hormone secretion in the pituitary. The present work determined whether endogenous vasopressin plays a role in response to repeated restraint. The first experiment explored changes in the response of repeatedly stressed animals to intracerebral vasopressin infusions. The second determined the effect of pretreating rats with a vasopressin V1a receptor antagonist on the way that they adapted to repeated restraint. Experiment 1: rats were subjected either to daily 60-min restraint for 10 days or transferred to the testing room where restraint sessions took place (controls). On the 11th day, they were infused with either artificial cerebrospinal fluid or 250 pmol vasopressin. The behavioural response to vasopressin was unaltered by previous stress. Plasma corticosterone was lowered in vasopressin-treated rats only after previous stress. Sixty minutes after vasopressin infusion, the central amygdala, locus coeruleus, the nucleus of the solitary tract and the dorsal vagal nucleus expressed increased levels of c-fos, and there were significant two-way interactions between stress and infusion for dorsal paraventricular nucleus, locus coeruleus and dorsal vagal nucleus. One-way analysis suggested that previous stress also reduced the c-fos response to vasopressin in the nucleus of the solitary tract. These results show that previous stress causes differential alterations in behavioural, endocrine and cellular responses to vasopressin. Experiment 2: rats were implanted with a transmitter which monitored heart rate and core temperature and a lateral cerebroventricular cannula. For 10 days, either artificial cerebrospinal fluid or 2500 pmol V1a antagonist, [d(CH2)1(5)-O-Me-Tyr2-Arg8]-vasopressin were infused i.c.v. 10 min prior to a 60-min restraint session. On the 11th day, no infusions were carried out, but rats received the usual period of restraint. The vasopressin antagonist was followed by motor responses (freezing, grooming and burrowing), more evident during the third and fifth days of stress. Core temperature responses were altered by the antagonist: stress-induced hypothermia was greatly reduced. Reduced baseline core temperatures, observed in controls as successive stress proceeded, were absent in antagonist-treated rats. By contrast, there were no significant effects of vasopressin antagonism on stress-induced tachycardia, nor in the way that this adapted to repeated restraint. On the 11th day (no i.c.v. infusions), hypothermic responses were no different in rats previously receiving either antagonist or control vehicle, but secondary hyperthermia was greater in the first group. Corticosterone levels were not altered by previous i.c.v. infusions.(ABSTRACT TRUNCATED AT 400 WORDS)
authors.affiliation: Department of Anatomy, University of Cambridge, U.K.
authors.forename: X
authors.initials: X
authors.lastname: Chen
authors.forename: J
authors.initials: J
authors.lastname: Herbert
mesh_terms: D000222:Adaptation, Physiological / Q000187:drug effects; D000818:Animals; D065092:Antidiuretic Hormone Receptor Antagonists; D001127:Arginine Vasopressin / Q000031:analogs & derivatives* / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects; D003345:Corticosterone / Q000097:blood; D006339:Heart Rate / Q000187:drug effects; D007276:Injections, Intraventricular; D008297:Male; D010286:Paraventricular Hypothalamic Nucleus / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012149:Restraint, Physical; D013312:Stress, Physiological / Q000097:blood / Q000378:metabolism / Q000503:physiopathology*; D013696:Temperature; D013997:Time Factors; D014667:Vasopressins / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D065092:Antidiuretic Hormone Receptor Antagonists; D016760:Proto-Oncogene Proteins c-fos; D014667:Vasopressins; D001127:Arginine Vasopressin; C025043:vasopressin, 1-(1-mercaptocyclohexaneacetic acid)-2-(O- methyl-L-tyrosine)-8-L-arginine-; D003345:Corticosterone