Mu opioid receptor and orexin/hypocretin mRNA levels in the lateral hypothalamus and striatum are enhanced by morphine withdrawal

• Published in: Journal of endocrinology Vol. 191; no. 1; pp. 137 - 145
• Main Authors: Zhou, Yan, Bendor, Jacob, Hofmann, Lauren, Randesi, Matthew, Ho, Ann, Kreek, Mary Jeanne
• Format: Journal Article
• Language: English
• Published: Colchester BioScientifica 01-10-2006; Portland Press
• Subjects: Adrenocorticotropic Hormone - blood; Animals; Biological and medical sciences; Corticosterone - blood; Gene Expression; Hypothalamic Area, Lateral - chemistry; Hypothalamic Area, Lateral - metabolism; Intracellular Signaling Peptides and Proteins - genetics; Male; Medical sciences; Morphine - adverse effects; Morphine - pharmacology; Neostriatum - chemistry; Neostriatum - metabolism; Neuropeptides - genetics; Neuropharmacology; Neurotransmitters. Neurotransmission. Receptors; Orexins; Peptidergic system (neuropeptide, opioid peptide, opiates...). Adenosinergic and purinergic systems; Pharmacology. Drug treatments; Pituitary Gland, Anterior - chemistry; Pituitary Gland, Anterior - metabolism; Rats; Rats, Inbred F344; Receptors, Corticotropin-Releasing Hormone - genetics; Receptors, Opioid, mu - genetics; Regular papers; RNA, Messenger - analysis; Substance Withdrawal Syndrome - metabolism; Testosterone - blood; Rat; Hypothalamohypophysoadrenal axis; Rodentia; Central nervous system; μ Opioid receptor; Lateral hypothalamus; Morphine; Basal ganglion; Corpus striatum; Gene expression; Neuropeptide; Encephalon; Vertebrata; Mammalia; Adult animal; Withdrawal syndrome; Orexin
• ISSN: 0022-0795; 1479-6805
• DOI: 10.1677/joe.1.06960

In this study, we investigated the effects of acute morphine administration, chronic intermittent escalating-dose morphine administration and spontaneous withdrawal from chronic morphine on mRNA levels of mu opioid receptor (MOP-r), and the opioid peptides pro-opiomelanocortin (POMC) and preprodynorphin (ppDyn) in several key brain regions of the rat, associated with drug reward and motivated behaviors: lateral hypothalamus (lat.hyp), nucleus accumbens (NAc) core, amygdala, and caudate–putamen (CPu). There was no effect on MOP-r mRNA levels in these brain regions 30 min after either a single injection of morphine (10 mg/kg, i.p.) or chronic intermittent escalating-dose morphine (from 7.5 mg/kg per day on day 1 up to 120 mg/kg per day on day 10). Activation of the stress-responsive hypothalamic–pituitary–adrenal axis by 12 h withdrawal from chronic morphine was confirmed; both POMC mRNA levels in the anterior pituitary and plasma adrenocorticotropic hormone levels were significantly elevated. Under this withdrawal-related stress condition, there was an increase in MOP-r mRNA levels in the lat.hyp, NAc core, and CPu. Recent studies have demonstrated a novel role for the lat.hyp orexin (or hypocretin) activation in both drug-related positive rewarding, and withdrawal effects. Around 50% of lat.hyp orexin neurons express MOP-r. Therefore, we also examined the levels of lat.hyp orexin mRNA, and found them increased in morphine withdrawal, whereas there was no change in levels of the lat.hyp ppDyn mRNA, a gene coexpressed with the lat.hyp orexin. Our results show that there is an increase in MOP-r gene expression in a region-specific manner during morphine withdrawal, and support the hypothesis that increased lat.hyp orexin activity plays a role in morphine-withdrawal-related behaviors.