THE INVOLVEMENT OF ADENOSINE RECEPTORS IN THE EFFECT OF DIZOCILPINE ON MICE IN THE ELEVATED PLUS-MAZE

It has been claimed that blockade of receptors for N-methyl-D-aspartat e (NMDA) can enhance adenosine receptor function on single neurones. P revious work has also indicated that the NMDA channel blocker dizocilp ine, and the A(1) selective agonist N6-cyclopentyladenosine (CPA) both had anxiolytic profiles in the elevated plus-maze. The anxiolytic eff ect of dizocilpine was accompanied by an increase in locomotor activit y. In the present study, the elevated plus-maze has been used to deter mine whether dizocilpine's effects on behaviour are mediated through a ctivation of adenosine receptors. When co-administered with dizocilpin e (0.05 mg/kg), CPA (0.05 mg/kg) reduced the anxiolytic and locomotor effects of dizocilpine. The A(1) selective antagonist 1,3-dipropyl-8-c yclopentylxanthine (CPX, 0.05 mg/kg) had no effect when administered a lone. When co-administered with dizocilpine, CPX reversed the anxiolyt ic and increased locomotor effects induced by dizocilpine. The A(2) re ceptor selective agonist -dimethoxyphenyl)-2(2-methylphenyl)-ethyladen osine (DPMA) (1 mg/kg) reversed both the anxiolytic effect and the inc reased locomotion induced by dizocilpine, while the A(2) selective ant agonist 3,7-dimethyl-1-propargylxanthine (DMPX) (1 mg/kg) did not. It is concluded that at least part of the anxiolytic and locomotor stimul ant properties of dizocilpine may be explained by the release of endog enous adenosine acting at A1, but not A2 receptors. (C) 1997 Elsevier Science B.V.