Effects of adenosine receptor agents on the expression of morphine withdrawal in mice

Effects of different doses of adenosine receptor agonists and antagonists on naloxone-induced jumping and diarrhea in morphine-dependent mice were studied. The adenosine A 1 receptor agonists, N 6 -cyclohexyladenosine (CHA: 0.1, 0.25 and 0.5 mg kg −1 ) and R -isomer of N 6 -phenylisopropyladenosine (R-PIA: 0.1, 0.3 and 1 mg kg −1 ), decreased jumping and diarrhea induced by naloxone in morphine-dependent mice. The adenosine A 1 receptor antagonist, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX: 0.3–9 mg kg −1 ), increased jumping but decreased diarrhea. The adenosine A 2 receptor agonist, 5′-( N -cyclopropyl)-carboxamidoadenosine (CPCA), decreased jumping and diarrhea. However, the adenosine A 2 receptor antagonist, 3,7-dimethyl-1-propargylxanthine (DMPX: 0.5 and 1 mg kg −1 ), did not elicit any response in this respect. DPCPX (0.3 and 3 mg kg −1 ), decreased the inhibition of jumping and diarrhea induced by CHA (0.5 mg kg −1 ), while DMPX (0.5 and 1 mg kg −1 ), decreased the inhibition of diarrhea induced by CPCA (0.1 mg kg −1 ). It is concluded that jumping induced by naloxone in morphine-dependent mice may be modified by the adenosine A 1 receptor mechanism(s) and diarrhea induced by the opioid receptor antagonist could be mediated by the adenosine A 1 and A 2 receptors.