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

Oct 27, 2006The Journal of endocrinology

Morphine withdrawal increases opioid and wakefulness-related messenger RNA in brain areas controlling motivation and reward

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Abstract

Acute morphine administration did not affect mu opioid receptor mRNA levels in key brain regions, while withdrawal from chronic morphine increased these levels in a region-specific manner.

No changes in mu opioid receptor mRNA levels were observed 30 minutes after a single or chronic morphine administration.
Significant elevation of pro-opiomelanocortin mRNA levels occurred in the anterior pituitary following 12 hours of withdrawal from chronic morphine.
Plasma adrenocorticotropic hormone levels were also significantly elevated during morphine withdrawal.
Increased mu opioid receptor mRNA levels were noted in the lateral hypothalamus, nucleus accumbens core, and caudate-putamen during withdrawal.
Orexin mRNA levels in the lateral hypothalamus increased during morphine withdrawal, while no change in preprodynorphin mRNA levels was found.
Findings support the potential role of increased lateral hypothalamus orexin activity in morphine-withdrawal-related behaviors.

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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.

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

Abstract

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