BACKGROUND AND OBJECTIVE: Morphine withdrawal increases the neuronal activity in the brain associated with the changes in the level of neurotransmitters and second messenger system. The aim of this study was to evaluate the effect of felodipine (calcium channel blocker) alone and in combination with CCPA (A1 receptor agonist) or SCH58261 (A2A receptor antagonist) on the morphine withdrawal syndrome.

METHODS: This experimental study was conducted on 80 NMRI male mice divided into 8 groups (n=10) including Saline, Felodipine (2.5, 5, 10 mg/kg), CCPA, SCH58261, Felodipine+CCPA, and Felodipine+SCH groups. Animals received increasing doses of morphine sulphate subcutaneously (S.C). Animals were examined in terms of jumping behavior and diarrhea for 30 minutes after intraperitoneal (i.p.) injection of naloxone (4 mg/kg i.p.).

FINDINGS: In comparison with the saline group, 5 mg/kg of Felodipine (88.1±7.199 & 44.8± 8.421, p<0.05), CCPA (88.1±7.199 & 20.4± 5.02, p<0.001) and SCH (88.1±7.199 & 37.2± 3.623, p<0.001) significantly reduced the number of jumps. Three doses (2.5, 5 and 10 mg/kg) of felodipine decreased the amount of diarrhea (0.478±0.059, 0.109±0.035, p<0.001), (0.478±0.059, 0.112±0.054, p<0.001), (0.478±0.059, 0.067±0.026, p<0.001), respectively and the CCPA significantly reduced diarrhea (0.478±0.059, 0.057±0.010, p<0.001), too. In the combination therapy, Felodipine (5mg/kg) +CCPA significantly decreased jumping (88.1±7.199 & 28.3±4.758, p<0.001) and diarrhea (0.478±0.59 & 0.011±0.007, p<0.001). Felodipine (5mg/kg) +SCH 58261 significantly reduced jumping (88.1±7.199 & 41.7±5.226, p<0.001) and diarrhea (0.478±0.59 & 0.027±0.023, p<0.001).

CONCLUSION: The results showed that using the felodipine in combination with SCH58261 and CCPA decreased morphine withdrawal symptoms, but synergistic effect was not observed in combination therapy.