Adenosine A1 receptors modulate anxiety in CD1 mice

Abstract

The effect of the selective adenosine A₁ receptor agonist 2-chloro-N ⁶-cyclopentyladenosine (CCPA) was investigated in CD1 mice by the elevated plus-maze and the light/dark test, two models for measuring anxiety in rodents. CCPA, administered IP, had an anxiolytic effect at 0.3 nmol/kg in the elevated plus-maze and at 1 nmol/kg in the light/dark test. 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 A₁ but not A₂ receptors by CCPA, and suggest that the anxiolytic-like action of CCPA may be mediated by centrally located adenosine A₁ receptors. Both CPT, a selective adenosine A₁ receptor antagonist, and IBMX, a non-selective adenosine antagonist, had an anxiogenic effect in the two tests. It is thus possible that purinergic neurons may be involved in the tonic modulation of affective state in mice.