Abstract:

Objective: The present study was designed to investigate the effects of imidazoline (I) receptors, especially I2 subtype, in in vivo morphine dependence. Methods: In vivo study was done by observing behavioural signs of morphine withdrawal in morphine dependent rats after treatment with selective I2 receptor agonist 2-BFI and selective I2 receptor antagonist BU224. Two morphine pellets, each containing 75 mg of morphine base, were implanted subcutaneously in the scapular area of Sprague-Dawley rats. Seventy-two hours after morphine implantation, 2-BFI (3, 5, 10 mg/kg), BU224 (3, 5, 10 mg/kg) or saline was injected to rats intraperitoneally (i.p.). Thirty minutes later, a morphine withdrawal syndrome was precipitated by naloxone (2 mg/kg). Just after the naloxone injection, morphine withdrawal signs such as jumping, wet dog shakes, teeth chattering, defecation, diarrhea, tremor and ptosis were observed and evaluated for 15 min. Results: Both 2-BFI and BU224, which are administered before naloxone-precipitated withdrawal syndrome, attenuated withdrawal symptoms dose dependently. Low doses of 2-BFI (3 mg/kg) on jumping and low dose of BU224 were found ineffective on wet dog shakes and weight lost. Conclusion: The present study showed that both 2-BFI and BU224 attenuated the intensity of many signs of the naloxoneprecipitated morphine withdrawal syndrome in rats. Based on these findings, it is thought that imidazoline system may play an important role in morphine dependence and morphine withdrawal, via it’s receptors or/and other mechanisms.

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