A detailed behavioral analysis of the acute motor effects of caffeine in the rat: involvement of adenosine

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-dimethyl- xanthine (CPT; 1.2, 4.8 and 7.2 mg/kg), and A2A receptor antagonist 3-(3-hydroxypropyl)-8-(m-methoxystyryl)-7-meth- yl-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 -cyclopentyla- denosine (CPA; 0.1 mg/g) and the selective A2A receptor agonist 2-p-(2-carboxyethyl)phenethylamino-5'-N-ethylcar- boxyamidoadenosine (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 be- havioral activation induced by caffeine was better mim- icked 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 A1receptors in the motor-activating effects of acutely administered caffeine.