Previous studies have demonstrated a role for
adenosine in mediating
opiate effects.
Adenosine receptors and their functions have been shown to be regulated by chronic
opiate treatment. This study examines the role of
adenosine receptors in the expression of
opiate withdrawal behaviors. The effects of single doses of parenterally administered
adenosine receptor subtype-selective agonists and antagonists on
opiate withdrawal signs in
morphine-dependent mice were measured. Mice received subcutaneous
morphine pellet treatment for 72 h and then underwent
naloxone-precipitated withdrawal after pretreatment with adenosinergic agents.
Adenosine agonists attenuated different
opiate withdrawal signs. The A1 agonist R-N6(phenylisopropyl)adenosine (0, 0.01, 0.02 mg/kg, IP) significantly reduced wet dog shakes and withdrawal
diarrhea, while the A2a-selective agonist 2-p-(2-carboxethyl)phenylethylamino-5'-N-ethylcarboxamido
adenosine or
CGS 21680 (0, 0.01, 0.05 mg/kg, IP) significantly inhibited teeth chattering and forepaw treads.
Adenosine receptor antagonists enhanced different
opiate withdrawal signs. The
adenosine A1 antagonist
1,3-dipropyl-8-cyclopentylxanthine (0, 1, 10 mg/kg, IP) significantly increased
weight loss and the A2 antagonist,
3,7-dimethyl-1-propargylxanthine (0, 1 and 10 mg/kg, IP) enhanced wet dog shakes and withdrawal
diarrhea. Treatment effects of adenosinergic agents were not due to nonspecific motor effects, as demonstrated by activity monitoring studies. These results support a role for
adenosine receptors in the expression of
opiate withdrawal and suggest the potential utility of
adenosine agonists in its treatment.