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The Journal of Neuroscience, February 1, 2000, 20(3):1272-1280

Local Morphine Withdrawal Increases c-fos Gene, Fos Protein, and Oxytocin Gene Expression in Hypothalamic Magnocellular Neurosecretory Cells

Louise E. Johnstone¹, Colin H. Brown¹, Hanneke K. M. Meeren¹, Chrétienne L. Vuijst¹, Philip J. Brooks², Gareth Leng¹, and John A. Russell¹

¹ Department of Biomedical Sciences, University Medical School, Edinburgh, EH8 9XD, Scotland, United Kingdom, and ² National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Rockville, Maryland 20852

We measured stimulation of c-fos and oxytocin gene expression during excitation of oxytocin cells induced by systemic or local morphine withdrawal. Female rats were made morphine-dependent by intracerebroventricular morphine infusion over 5 d. Morphine withdrawal, induced by systemic injection of the opioid antagonist naloxone (5 mg/kg) in conscious or anesthetized rats, increased the density of c-fos messenger RNA and of oxytocin heterogeneous nuclear RNA in supraoptic nucleus cells compared with those of nonwithdrawn rats; c-fos messenger RNA was also increased in the magnocellular and parvocellular paraventricular nuclei of withdrawn rats. Morphine withdrawal increased the number of Fos-immunoreactive cells in the supraoptic and magnocellular paraventricular nuclei of conscious or pentobarbitone-anesthetized rats. Morphine withdrawal also increased Fos-immunoreactive cell numbers in the parvocellular paraventricular nucleus of conscious but not anesthetized rats. Central administration of the ₁-adrenoreceptor antagonist benoxathian (5 µg/min) did not prevent morphine withdrawal-induced increases in the numbers of Fos-immunoreactive neurons in the supraoptic or magnocellular paraventricular nucleus. Unilateral microdialysis administration of naloxone (10⁵ M) into the supraoptic nucleus of anesthetized morphine-dependent rats increased Fos-immunoreactive cell numbers compared with the contralateral nucleus. Finally, we investigated whether dependence could be induced by chronic unilateral infusion of morphine into a supraoptic nucleus; systemic naloxone (5 mg/kg) increased Fos-immunoreactive cell numbers in the morphine-infused nucleus compared with the contralateral nucleus. Thus, morphine withdrawal excitation increases c-fos and oxytocin gene expression in supraoptic nucleus neurons. This occurs independently from excitation of their ascending noradrenergic inputs, and both dependence and withdrawal can be induced within the supraoptic nucleus.

Key words: adrenoreceptors; benoxathian; dependence; hypothalamic paraventricular nucleus; microdialysis; naloxone; opioid; supraoptic nucleus

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Copyright © 2000 Society for Neuroscience  0270-6474/00/2031272-09$05.00/0

This article has been cited by other articles:

				C. Yue, N. Mutsuga, E. M. Scordalakes, and H. Gainer Studies of oxytocin and vasopressin gene expression in the rat hypothalamus using exon- and intron-specific probes Am J Physiol Regulatory Integrative Comp Physiol, May 1, 2006; 290(5): R1233 - R1241. [Abstract] [Full Text] [PDF]

				O. E. Malakhova and P. W. Davenport c-Fos expression in the central nervous system elicited by phrenic nerve stimulation J Appl Physiol, April 1, 2001; 90(4): 1291 - 1298. [Abstract] [Full Text] [PDF]

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