NECA-induced hypomotility in mice: evidence for a predominantly central site of action

The behavioral effects of four adenosine analogues (NECA, CHA, CPA and CV-1808) were investigated in mice using a holeboard test, which measures both directed exploration (head-dipping) and a locomotor activity. NECA, CHA and CPA showed significant dose-related reductions in all the holeboard measures (NECA much greater than CHA = CPA), whilst CV-1808 showed no significant effect on any of the measures over the dose range tested. In a subsequent experiment NECA-induced hypomotility was attenuated by the adenosine receptor antagonists, theophylline (which is both centrally and peripherally active) and, though to a lesser extent, by the adenosine receptor antagonist 8-(p-sulfophenyl)theophylline (8-pSPT), which poorly penetrates the blood-brain barrier. The results suggest that NECA-induced hypomotility may be predominantly mediated centrally since the centrally active antagonist was the most effective in reversing the effect, however, peripheral mechanisms may also play a role since equimolar concentrations of 8-pSPT elicit some reversal of NECA-induced hypomotility.