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.
Durcan
M J
MJ
Laboratory of Clinical Studies, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD 20892.
Morgan
P F
PF
D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D019830:Adenosine-5'-(N-ethylcarboxamide); D000818:Animals; D002490:Central Nervous System / Q000187:drug effects*; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects*; D011983:Receptors, Purinergic / Q000378:metabolism; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology
D011983:Receptors, Purinergic; D019830:Adenosine-5'-(N-ethylcarboxamide); C027513:N(6)-cyclohexyladenosine; C048599:N(6)-cyclopentyladenosine; C031433:8-(4-sulfophenyl)theophylline; D013806:Theophylline; C026708:2-phenylaminoadenosine; D000241:Adenosine