The effect of O-1602, an atypical cannabinoid, on morphine-induced conditioned place preference and physical dependence

详细信息    查看全文

• 作者：Mohaddeseh Sadat Alavi^a ; Hossein Hosseinzadeh^b ; Ali Shamsizadeh^c ; Ali Roohbakhsh^b ; ^{roohbakhsha@mums.ac.ir" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Morphine ; GPR55 protein ; Opiate dependence ; O-1602 ; Reward
• 刊名：Pharmacological Reports
• 出版年：2016
• 出版时间：June 2016
• 年：2016
• 卷：68
• 期：3
• 页码：592-597
• 全文大小：401 K

文摘

Previous studies show that some non-CB1/non-CB2 effects of cannabinoids are mediated through G protein coupled receptor 55 (GPR55). As this receptor is activated by some of cannabinoid receptor ligands and is involved in the modulation of pain, it was hypothesized that this receptor may also interact with opioids. This study examined the effect of atypical cannabinoid O-1602 as a GPR55 agonist on morphine-induced conditioned place preference (CPP) and physical dependence.

Methods

We used a biased CPP model to evaluate the effect of O-1602 (0.2, 1 and 5 mg/kg, intraperitoneal; ip) on the acquisition and expression of morphine-induced CPP in male mice. The locomotor activities of mice were also recorded. Moreover, repeated administration of morphine (50, 50 and 75 mg/kg/day) for three days, induced physical dependence. The withdrawal signs such as jumps and diarrhea were precipitated by administration of naloxone (5 mg/kg, ip). The effect of O-1602 on the development of morphine physical dependence was assessed by injection of O-1602 (0.2, 1 and 5 mg/kg) before morphine administrations.

Results

Morphine (40 mg/kg, subcutaneous; sc), but not O-1602 (5 mg/kg) elicited significant preference in the post-conditioning phase. O-1602 at the doses of 0.2 and 1 mg/kg, but not 5 mg/kg reduced acquisition of morphine CPP with an increase in locomotor activity at the dose of 5 mg/kg. O-1602 at the doses of 0.2, 1 and 5 mg/kg also reduced expression of morphine CPP with an increase in locomotor activity at the dose of 5 mg/kg. O-1602 had a significant inhibitory effect on development of morphine-induced physical dependence at the dose of 5 mg/kg by decreasing jumps and diarrhea during withdrawal syndrome.

Conclusions

The present results indicate that O-1602 decreased acquisition and expression of morphine CPP and inhibited development of morphine-induced physical dependence.