ADENOSINE A(1) RECEPTORS MODULATE ANXIETY IN CD1 MICE

The effect of the selective adenosine Al receptor agonist 2-chloro-N-6 -cyclopentyladenosine (CCPA) was investigated in CD1 mice by the eleva ted plus-maze and the light/dark test, two models for measuring anxiet y in rodents. CCPA, administered IP, had an anxiolytic effect at 0.3 n mol/kg in the elevated plus-maze and at 1 nmol/kg in the light/dark te st. Brain levels of 22 nM were found after administration of 100 nmol/ kg CCPA, as measured by ex vivo binding experiments. These values are consistent with the occupancy of adenosine A(1) but not A(2) receptors by CCPA, and suggest that the anxiolytic-like action of CCPA may be m ediated by centrally located adenosine A(1) receptors. Both CPT, a sel ective adenosine A(1) receptor antagonist, and IBMX, a non-selective a denosine antagonist, had an anxiogenic effect in the two tests. It is thus possible that purinergic neurons may be involved in the tonic mod ulation of affective state in mice.