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A detailed behavioral analysis of the acute motor effects of caffeine in the rat: involvement of adenosine A1 and A2A receptors

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Abstract

Rationale

There is no consensus on the contribution of adenosine A1 and A2A receptor blockade to motor-activating effects of caffeine.

Objective

Our aim was to use a detailed and continuous observational method to compare the motor effects induced by caffeine with those induced by selective A1 and A2A receptor antagonists.

Methods

The behavioral repertoire induced by systemic administration of caffeine (3, 10, and 30 mg/kg), A1 receptor antagonist 8-cyclopentyl-1,3-dimethylxanthine (CPT; 1.2, 4.8 and 7.2 mg/kg), and A2A receptor antagonist 3-(3-hydroxypropyl)-8-(m-methoxystyryl)-7-methyl-1-propargylxanthine phosphate disodium salt (MSX-3; 1, 3, and 10 mg/kg) was analyzed. The effects of pretreatment with the selective A1 receptor agonist N 6-cyclopentyladenosine (CPA; 0.1 mg/g) and the selective A2A receptor agonist 2-p-(2-carboxyethyl)phenethylamino-5′-N-ethylcarboxyamidoadenosine (CGS 21680; 0.2 mg/kg) on the pattern of motor activation induced by caffeine, CPT, or MSX-3 were also examined.

Results

The pattern of behavioral activation induced by caffeine was better mimicked by CPT than by MSX-3. Coadministration of CPT and MSX-3 gave different results depending on the dose and the type of behavioral response. CPA was more effective at decreasing the activating effects of caffeine and CPT than those of CGS 21680. On the other hand, CGS 21680 was more effective at decreasing the activating effects of MSX-3 than those of caffeine or CPT. Factor analysis revealed a complex three-dimensional behavioral profile for caffeine that was similar to the profile for CPT and was different from the profile for MSX-3.

Conclusions

The results indicate a predominant role for A1 receptors in the motor-activating effects of acutely administered caffeine.

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Acknowledgements

We would like to thank Mrs. Olga Tsoumami for technical assistance. National Institute on Drug Abuse Intramural Research Program funds supported this research.

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Correspondence to Sergi Ferré.

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Antoniou, K., Papadopoulou-Daifoti, Z., Hyphantis, T. et al. A detailed behavioral analysis of the acute motor effects of caffeine in the rat: involvement of adenosine A1 and A2A receptors. Psychopharmacology 183, 154–162 (2005). https://doi.org/10.1007/s00213-005-0173-6

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  • DOI: https://doi.org/10.1007/s00213-005-0173-6

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