Circadian alteration in neurobiology during protracted opiate withdrawal in rats

Decreased locomotor activity and elevated adrenocorticotropic hormone and melatonin levels persisted for 60 days after morphine withdrawal.

• Protracted opiate withdrawal is associated with disrupted hormonal circadian rhythms lasting up to two months.
• Corticosterone levels were elevated only at 36 hours and 10 days post-withdrawal, while orexin levels were high initially but reversed to low levels during withdrawal.
• Circadian rhythms for adrenocorticotropic hormone, corticosterone, and orexin remained blunted for at least 60 days.
• The circadian rhythm of beta-endorphin and melatonin showed recovery by day 60, but the peak phase of beta-endorphin was delayed by about 8 hours.
• Reduced expression of clock genes rPER1, rPER2, and rPER3 persisted in several brain regions for at least 60 days.

AI simplified