Behavioral characteristics of centrally administered adenosine analogs.

Mice were implanted with chronic indwelling cannulae in the lateral cerebral ventricle. A series of adenosine analogs and related compounds were injected into the lateral ventricle (ICVT) and their effects on spontaneous locomotor activity recorded. All analogs produced dose-related decreases in locomotor activity. 5'-N6-ethyl-carboxamidoadenosine (NECA) was the most potent compound tested, with a number of N6-substituted analogs also being effective depressants of activity. Caffeine, administered either intracerebroventricularly or intraperitoneally, antagonized the depressant effects of the adenosine analogs. 3-Isobutyl-1-methylxanthine, administered ICVT, depressed locomotor activity. However, after caffeine, IBMX elicited behavioral stimulation. Agents which inhibit the transport of adenosine (dipyridamole, dilazep, papaverine) depressed locomotor activity, as did erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA, an inhibitor of adenosine deaminase. The effects of dilazep, papaverine and EHNA, but not of dipyridamole, were antagonized by caffeine. These results further substantiate the notion that endogenous adenosine is involved in the regulation of central nervous system excitability.