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Differential Changes in Expression of Stress- and Metabolic-related Neuropeptides in the Rat Hypothalamus during Morphine Dependence and Withdrawal

PintĂŠr-KĂźbler, Bernadett

Ferenczi, SzilamĂŠr

Nunez, Cristina

Zelei, Edina

Polyåk, Ágnes

Milanes, Victoria M.

KovĂĄcs, Krisztina J.

Public Library of Science

2013

RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry / idegkĂłrtan, neurolĂłgia, pszichiĂĄtria

Chronic morphine treatment and naloxone precipitated morphine withdrawal activates stress-related brain circuit and results in significant changes in food intake, body weight gain and energy metabolism. The present study aimed to reveal hypothalamic mechanisms underlying these effects. Adult male rats were made dependent on morphine by subcutaneous implantation of constant release drug pellets. Pair feeding revealed significantly smaller weight loss of morphine treated rats compared to placebo implanted animals whose food consumption was limited to that eaten by morphine implanted pairs. These results suggest reduced energy expenditure of morphine-treated animals. Chronic morphine exposure or pair feeding did not significantly affect hypothalamic expression of selected stress- and metabolic related neuropeptides - corticotropin-releasing hormone (CRH), urocortin 2 (UCN2) and proopiomelanocortin (POMC) compared to placebo implanted and pair fed animals.
Naloxone precipitated morphine withdrawal resulted in a dramatic weight loss starting as early as 15-30 min after naloxone injection and increased adrenocorticotrophic hormone, prolactin and corticosterone plasma levels in morphine dependent rats. Using real-time quantitative PCR to monitor the time course of relative expression of neuropeptide mRNAs in the hypothalamus we found elevated CRH and UCN2 mRNA and dramatically reduced POMC expression. Neuropeptide Y (NPY) and arginine vasopressin (AVP) mRNA levels were transiently increased during opiate withdrawal. These data highlight that morphine withdrawal differentially affects expression of stress- and metabolic-related neuropeptides in the rat hypothalamus, while relative mRNA levels of these neuropeptides remain unchanged either in rats chronically treated with morphine or in their pair-fed controls.

magyar

Article

PeerReviewed

info:eu-repo/semantics/article

text

http://real.mtak.hu/5513/1/PlosOne%20final_REALba.pdf

PintÊr-Kßbler, Bernadett and Ferenczi, SzilamÊr and Nunez, Cristina and Zelei, Edina and Polyåk, Ágnes and Milanes, Victoria M. and Kovåcs, Krisztina J. (2013) Differential Changes in Expression of Stress- and Metabolic-related Neuropeptides in the Rat Hypothalamus during Morphine Dependence and Withdrawal. PLoS ONE, 8 (6). e67027. ISSN 1932-6203

http://real.mtak.hu/5513/