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 A1 receptor agonists, N6-cyclohexyladenosine (CHA: 0.1, 0.25 and 0.5 mg kg(-1)) and R-isomer of N6-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 A1 receptor antagonist, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX: 0.3-9 mg kg(-1)), increased jumping but decreased diarrhea. The adenosine A2 receptor agonist, 5'-(N-cyclopropyl)-carboxamidoadenosine (CPCA), decreased jumping and diarrhea. However, the adenosine A2 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 receptor mechanism(s) and diarrhea induced by the opioid receptor antagonist could be mediated by the adenosine A1 and A2 receptors.

Potentiation of licking in rats by stimulation of both D-1 and D-2 dopamine receptors.

Apomorphine-induced licking in rats was assessed by recording the total number of licks by direct observation. Apomorphine induced licking dose dependently. The maximum response was obtained by 0.5 mg/kg of the drug and 30 min after drug administration. Pre-treatment with dopamine antagonists, sulpiride and SCH 23390 decreased the apomorphine effect. Pre-treatment of animals with reserpine+α-methyl-p-tyrosine (AMPT) increased apomorphine-induced licking. In normal rats the D-2 agonist quinpirole and the D-1 agonist SKF 38393 also induced significant licking. The effect of quinpirole or SKF 38393 was decreased by reserpine+AMPT pre-treatment. Combined treatment with SKF 38393 and quinpirole induced more intense licking in both reserpinized and non-reserpinized animals. It is therefore concluded that the apomorphine-induced licking is mediated through both D-1 and D-2 receptors, and that pre-treatment with reserpine hypersensitizes these receptors to the drug effect. However, for either SKF 38393- or quinpirole-induced licking, the presence of endogenous dopamine seems essential.