Anxiolytic activity of adenosine receptor activation in mice

Article date: October 1995

By: Nisha Jain, Nicola Kemp, Olasumbo Adeyemo, Patricia Buchanan, Trevor W. Stone, in Volume 116, Issue 3, pages 2127-2133

Purine analogues have been examined for anxiolytic‐ and anxiogenic‐like activity in mice, by use of the elevated plus‐maze.

The selective A1 receptor agonist, N6‐cyclopentyladenosine (CPA) had marked anxiolytic‐like activity at 10 and 50 μ kg−1, with no effect on locomotor performance at these doses.

The A1 selective adenosine receptor antagonist, 1,3‐dipropyl‐8‐cyclopentylxanthine (CPX) had no significant effect on anxiety‐related measures or locomotor behaviour, but blocked the anxiolytic‐like activity of CPA. The hydrophilk xanthine, 8‐(p‐sulphophenyl) theophylline did not prevent anxiolysis by CPA.

Caffeine had anxiogenic‐like activity at 30 mg kg−1 which was prevented by CPA at 50 μg kg−1.

The A2 receptor agonist, N6‐[2‐(3,5‐dimethoxyphenyl)‐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 A2 receptor antagonist, 1,3‐dimethyl‐l‐propargylxanthine (DMPX) had no effect on anxiety‐related measures or locomotion and did not modify the anxiolytic‐like activity of CPA.

Administration of DPMA in combination with anxiolytic doses of CPA prevented the anxiolytic‐like activity of the latter.

The results suggest that the selective activation of central A1 adenosine receptors induces anxiolytic‐like behaviour, while the activation of A2 sites causes locomotor depression and reduces the effects of A1 receptor activation. The absence of any effect of CPX alone suggests that the receptors involved in modulating behaviour in the elevated plus‐maze in mice are not activated tonically by endogenous adenosine.

Purine analogues have been examined for anxiolytic‐ and anxiogenic‐like activity in mice, by use of the elevated plus‐maze.

The selective A1 receptor agonist, N6‐cyclopentyladenosine (CPA) had marked anxiolytic‐like activity at 10 and 50 μ kg−1, with no effect on locomotor performance at these doses.

The A1 selective adenosine receptor antagonist, 1,3‐dipropyl‐8‐cyclopentylxanthine (CPX) had no significant effect on anxiety‐related measures or locomotor behaviour, but blocked the anxiolytic‐like activity of CPA. The hydrophilk xanthine, 8‐(p‐sulphophenyl) theophylline did not prevent anxiolysis by CPA.

Caffeine had anxiogenic‐like activity at 30 mg kg−1 which was prevented by CPA at 50 μg kg−1.

The A2 receptor agonist, N6‐[2‐(3,5‐dimethoxyphenyl)‐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 A2 receptor antagonist, 1,3‐dimethyl‐l‐propargylxanthine (DMPX) had no effect on anxiety‐related measures or locomotion and did not modify the anxiolytic‐like activity of CPA.

Administration of DPMA in combination with anxiolytic doses of CPA prevented the anxiolytic‐like activity of the latter.

The results suggest that the selective activation of central A1 adenosine receptors induces anxiolytic‐like behaviour, while the activation of A2 sites causes locomotor depression and reduces the effects of A1 receptor activation. The absence of any effect of CPX alone suggests that the receptors involved in modulating behaviour in the elevated plus‐maze in mice are not activated tonically by endogenous adenosine.

DOI: 10.1111/j.1476-5381.1995.tb16421.x

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