Gap junction blockers: a potential approach to attenuate morphine withdrawal symptoms

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.

Acute Administration of Pioglitazone Attenuates Morphine Withdrawal Syndrome in Rat: A Novel Role of Pioglitazone

“…The procedure of the administration was as follow: day 1: 5 mg/kg/12 h, days 2 and 3: 10 mg/ kg/12 h, days 4 and 5: 15 mg/kg/12 h, days 6 and 7: 20 mg/ kg/12 h, and days 8 and 9: 25 mg/kg/12 h. On the ninth day only the morning dose of morphine was injected. This morphine administration protocol showed a high degree of dependence creation in the rats [12,13]. Under the same condition, the rats in non-dependent groups were received only normal saline.…”

“…The locomotor activity was assessed in morphine pioglitazone (40 mg/kg) treated group by direct observation in an interval scale which measured the frequency of crossing the lines painted on the underside of the floor of the Plexiglas behavioral arena by each rat. This test was carried out before receiving morphine and 30 min after the pioglitazone (40 mg/kg) administration on the ninth day [13].…”

Attenuation of Morphine-Induced Tolerance and Dependence by Pretreatment with Cerebrolysin in Male rats

“…Non-dependent (control) group was treated with normal saline (twice daily, s.c). For induction of tolerance, additive doses of Morphine were administered for nine days as follow procedure: day 1: 5 mg/kg/12 h, days 2 and 3: 10 mg/kg/12 h, days 4 and 5: 15 mg/kg/12 h, days 6 and 7: 20 mg/kg/12 h, and days 8 and 9: 25 mg/kg/12 h [19,20]. Accordingly, three groups where received Cerebrolysin (40, 80 and 160 mg/kg, ip) before morphine administration to assess the attenuation effects of Cerebrolysin on the induction of tolerance, under the same condition.…”

Role of hippocampal CA1 area gap junction channels on morphine state-dependent learning

“…Recent studies have demonstrated that gap junctions (GJs) are probably involved in some of the effects of morphine in the central nervous system (Moradi et al, 2013;Nassiri asl M, 2011;Suzuki et al, 2006). For example, intracerebroventricular injections of GJ blockers, carbenoxolone (CBX) or mefloquine (MFQ) decreased morphine withdrawal signs significantly in rats (Moradi et al, 2013).…”

“…For example, intracerebroventricular injections of GJ blockers, carbenoxolone (CBX) or mefloquine (MFQ) decreased morphine withdrawal signs significantly in rats (Moradi et al, 2013).…”