The effect of carbenoxolone on morphine-induced withdrawal symptoms in rats

The exact mechanisms of morphine dependence and withdrawal syndrome remain unclear. Many studies have been performed to find a drug for prevention of withdrawal syndrome. The aim of this study was to evaluate the effect of carbenoxolone (a gap junction inhibitor) on morphine withdrawal syndrome in male rats. In this experimental study، adult male Sprague Dawley rats with weights between 225 and 275 g were selected randomly and divided into 8 groups. Each group consisted of 8 rats. In order to induce dependency، morphine was injected subcutaneously for nine days (1st day: 5mg/kg، 2nd and 3rd days: 10 mg/kg، 4th and 5th days: 15 mg/kg، 6th and 7th days: 20 mg/kg، 8th and 9th days: 25 mg/kg). On the ninth day only the morning dose of morphine was injected، then control group and treatment groups received IP injection of saline (1 ml/kg) and IP injection of carbenoxolone (5، 25، 50، 100 mg/kg) respectively. After 30 min all groups received IP injection of naloxone (4 mg/kg) and the withdrawal signs including: jumping، rearing، genital grooming، abdominal writhing، body grooming and wet dog shake، were recorded for 60 minutes. Our results showed that carbenoxolone not only decreased all withdrawal signs، but also reduced the total withdrawal scores، significantly. In conclusion we found that carbenoxolone as a gap junction inhibitor was effective in decreasing the symptoms of morphine withdrawal syndrome.