ANXIOLYTIC ACTIVITY OF ADENOSINE RECEPTOR ACTIVATION IN MICE

1 Purine analogues have been examined for anxiolytic- and anxiogenic-l ike activity in mice, by use of the elevated plus-maze. 2 The selectiv e A(1) receptor agonist, N-6-cyclopentyladenosine (CPA) had marked anx iolytic-like activity at 10 and 50 mu g kg(-1), with no effect on loco motor performance at these doses. 3 The A(1) selective adenosine recep tor antagonist, 1,3-dipropyl-8-cyclopentylxanthine (CPX) had no signif icant effect on anxiety-related measures or locomotor behaviour, but b locked the anxiolytic-like activity of CPA. The hydrophilic xanthine, 8-(p-sulphophenyl) theophylline did not prevent anxiolysis by CPA.4 Ca ffeine had anxiogenic-like activity at 30 mg kg(-1) which was prevente d by CPA at 50 mu g kg(-1). 5 The A(2) receptor agonist, imethoxypheny l)-2-(2-methylphenyl)-ethyl]adenosine (DPMA) had no effect on anxiety behaviour but depressed locomotor activity at the highest dose tested of 1 mg kg(-1). The A(2) receptor antagonist, 1,3-dimethyl-1-propargyl xanthine (DMPX) had no effect on anxiety-related measures or locomotio n and did not modify the anxiolytic-like activity of CPA. 6 Administra tion of DPMA in combination with anxiolytic doses of CPA prevented the anxiolptic-like activity of the latter. 7 The results suggest that th e selective activation of central A, adenosine receptors induces anxio lytic-like behaviour, while the activation of A(2) sites causes locomo tor depression and reduces the effects of A(1) receptor activation. Th e absence of any effect of CPX alone suggests that the receptors invol ved in modulating behaviour in the elevated plus-maze in mice are not activated tonically by endogenous adenosine.