The Effect of Dopaminergic Receptors Antagonist and CCPA (A1 Adenosine Receptor Agonist) or SCH58261 (A2a Adenosine Receptor Antagonist) on Morphine Withdrawal Syndrome

Morphine withdrawal induces a state of neuronal hyperexcitability in the brain which has been linked to changes in a number of second messenger systems and neurotransmitters. In the present study, the effects of chlorpromazine (dopamine receptor antagonist) alone or in combination with CCPA (A1 adenosine receptor agonist) or SCH58261 (A2a Adenosine receptor antagonist) were examined onmorphine withdrawal syndrome in mice. Materials and Methods: In this study, 80 NMRI male mice were allocated in 8 groups (n=10): saline, chlorpromazine (0.25, 0.5, 1.0 mg/kg), CCPA (0.5 mg/kg), SCH58261 (0.1 mg/kg), chlorpromazine (0.5 mg/kg) +CCPA, and chlorpromazine (0.5 mg/kg) +SCH. Animals were received different doses of morphine sulphate subcutaneously (s.c) and the withdrawal syndrome wasevoked by naloxone injection (4 mg/kg i.p.). Animals were observed for 30 min for jumping behavior and diarrhea. CCPA (0.5 mg/kg i.p.) and SCH 58261 (1 mg/kg i.p.) were given 10 min, and chlorpromazine 30 min before naloxone. In combination therapy micetreatedwith chlorpromazine 0.5 mg/kg and CCPA or SCH58261 before naloxone. Results: Administration of the dopamine D1/D2 receptor antagonist or chlorpromazine (0.25, 0.5 and 1 mg/kg) significantly decreased jumping (p<0.05) and diarrhea (p<0.001).Both CCPA and SCH 58261 significantly reduced jumping (p<0.001) and diarrhea (p<0.001). Combination therapy of chlorpromazine and CCPA or SCH58261 also significantly decreased jumping and diarrhea (p<0.001). Conclusion: It is concluded that blockade of both dopamine receptors with chlorpromazine may suppress naloxone-induced jumping and diarrhea in morphinedependent mice. Effect of combination therapy of chlorpromazine and CCPA or SCH58261 on jumping and diarrhea were not additive.