Abstract
BackgroundThe exact mechanisms of morphine-induced dependence and withdrawal symptoms remain unclear. In order to identify an agent that can prevent withdrawal syndrome, many studies have been performed. This study was aimed to evaluate the effect of gap junction blockers; carbenoxolone (CBX) or mefloquine (MFQ); on morphine withdrawal symptoms in male rat.Adult male Wistar rats (225 – 275 g) were selected randomly and divided into 10 groups. All groups underwent stereotaxic surgery and in order to induce dependency, morphine was administered subcutaneously) Sc) at an interval of 12 hours for nine continuous days. On the ninth day of the experiment, animals received vehicle or CBX (100, 400, 600 μg/10 μl/rat, icv) or MFQ (50, 100 and 200 μg/10 μl/rat, icv) after the last saline or morphine (Sc) injection. Morphine withdrawal symptoms were precipitated by naloxone hydrochloride 10 min after the treatments. The withdrawal signs including: jumping, rearing, genital grooming, abdomen writhing, wet dog shake and stool weight, were recorded for 60 minutes.ResultsResults showed that CBX and MFQ decreased all withdrawal signs; and the analysis indicated that they could attenuate the total withdrawal scores significantly.ConclusionTaking together it is concluded that gap junction blockers prevented naloxone-precipitated withdrawal symptoms.
Highlights
The exact mechanisms of morphine-induced dependence and withdrawal symptoms remain unclear
Data analysis indicated that the withdrawal signs including: jumping, Figure 3 Effects of icv injection of carbenoxolone (100, 400, 600 μg/rat) on the expression of naloxone (4 mg/kg)-induced total withdrawal score (TWS) in morphine-dependent rats
Effect of icv administration of mefloquine on morphine withdrawal signs Our findings in this study have shown that icv administration of mefloquine (50, 100 and 200 μg/10 μl/ rat) decreased all withdrawal signs significantly [Figure 4] (P < 0.001)
Summary
The exact mechanisms of morphine-induced dependence and withdrawal symptoms remain unclear. This study was aimed to evaluate the effect of gap junction blockers; carbenoxolone (CBX) or mefloquine (MFQ); on morphine withdrawal symptoms in male rat. All groups underwent stereotaxic surgery and in order to induce dependency, morphine was administered subcutaneously) Sc) at an interval of 12 hours for nine continuous days. It is well known that repeated administration of opiates results in physical dependence. Dependence is a behavioral state requiring continued drug administration to avoid a series of aversive withdrawal symptoms. New drugs and strategies are under investigation for preventing of opiate dependence as well as withdrawal signs in a wide variety of animal species. The neurotransmitter systems have been widely studied to find out the involved mechanisms of withdrawal symptoms. Several lines of evidence indicate the involvement of noradrenergic system in opiate
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