PMID: 2507846Jan 1, 1989Paper

Regulation by chronic clonidine of adenylate cyclase and cyclic AMP-dependent protein kinase in the rat locus coeruleus

Life Sciences
E J NestlerD Beitner

Abstract

Clonidine and morphine are known to produce tolerance and dependence in rat locus coeruleus (LC) neurons after chronic administration based on electrophysiological criteria. Previous studies have shown that morphine tolerance and dependence is associated with increases in levels of adenylate cyclase, pertussis toxin-mediated ADP-ribosylation of G-proteins, and cyclic AMP-dependent protein kinase in this brain region. The present study was aimed at investigating whether clonidine tolerance and dependence is also associated with alterations in these intracellular messengers. It was found that, similar to chronic morphine, chronic (2 weeks) clonidine administration, under conditions that produce electrophysiological evidence of tolerance and dependence in LC neurons, increased levels of adenylate cyclase activity and cyclic AMP-dependent protein kinase activity in this brain region, but not in several other regions studied, which included the frontal cortex, neostriatum, and dorsal raphe. However, the changes induced by chronic clonidine in the LC, at maximal doses and duration of treatment, were only approximately 50% in magnitude of those observed in response to morphine. Unlike chronic morphine, chronic clonidine produced no ch...Continue Reading

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Citations

May 1, 1997·Pharmacology, Biochemistry, and Behavior·K ReidM Maze
Oct 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·E J NestlerR S Duman
Dec 11, 1999·Brain Research. Brain Research Protocols·M A Bernstein, S P Welch
Dec 12, 2001·Neuroscience·E J Van Bockstaele, K G Commons
Jan 1, 1994·Brain Research Bulletin·E J NestlerG K Aghajanian
Mar 29, 2014·Autonomic & Autacoid Pharmacology·F RezaniaS Ejtemaei Mehr
Dec 1, 2007·European Journal of Pharmacology·Victoria L HallerSandra P Welch
Jan 28, 2015·Pediatrics·Henrietta S BadaPatrick Breheny

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