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Effects of morphine and morphine withdrawal on brainstem neurons innervating hypothalamic nuclei that control thepituitary‐adrenocortical axis in rats
Author(s) -
Laorden Maria Luisa,
Castells Maria Teresa,
Milanés Maria Victoria
Publication year - 2002
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0704684
Subject(s) - endocrinology , brainstem , hypothalamus , medicine , morphine , solitary tract , supraoptic nucleus , rostral ventromedial medulla , (+) naloxone , medulla , solitary nucleus , medulla oblongata , opioid , chemistry , stimulation , central nervous system , receptor , nociception , hyperalgesia
Different data support a role for brainstem noradrenergic inputs to the hypothalamic paraventricular nucleus (PVN) in the control of hypothalamus – pituitary – adrenocortical (HPA) axis. However, little is known regarding the functional adaptive changes of noradrenergic afferent innervating the PVN and supraoptic nucleus (SON) during chronic opioid exposure and upon morphine withdrawal. Here we have studied the expression of Fos after administration of morphine and during morphine withdrawal in the rat hypothalamic PVN and SON. Fos production was also studied in brainstem regions that innervate hypothalamic nuclei: the nucleus of solitary tract (NTS – A 2 ) and the ventrolateral medulla (VLM – A 1 ) and combined with immunostaining for tyrosine hydroxylase (TH) for immunohistochemical identification of active neurons during morphine withdrawal. Male rats were implanted with s.c. placebo or morphine (tolerant/dependent) pellets for 7 days. On day 8 rats received an injection of saline i.p., morphine i.p., saline s.c. or naloxone s.c. Acute morphine administration produced an increase in Fos expression at hypothalamic nuclei and in the brainstem regions, and tolerance developed towards this effect. Precipitated morphine withdrawal induced marked Fos immunoreactivity within the PVN and SON. Concomitantly, numerous neurons in the brainstem were stimulated by morphine withdrawal. Moreover, catecholaminergic‐positive neurons in the brainstem showed a significant increase in Fos expression in response to morphine withdrawal. These findings demonstrate that chronic activation of opioid receptors results in altered patterns of immediate‐early genes (IEG) expression in the PVN and SON, which occurs concurrently with an increased activity of their inputs from the brainstem.British Journal of Pharmacology (2002) 136 , 67–75; doi: 10.1038/sj.bjp.0704684