Agonists and antagonists of adenosine receptors and morphine withdrawal syndrome in rats.

The compounds activating adenosine system alleviated morphine withdrawal syndrome (the number of escape attempts and body shakes) in rats. Body shakes were decreased mostly by N-ethylcarboxamidoadenosine, cyclohexyladenosine, dipyridamole and 2-chloroadenosine, while R-phenylisopropyladenosine very strongly decreased the number of escape attempts. Adenosine receptor antagonists (caffeine and theophylline) increased the number of escape attempts in morphine-dependent rats. Caffeine (10 mg/kg), administered preventively, antagonized the inhibitory effects of adenosine analogs. These results suggest the existence of relation between opioid receptors and the adenosine system.