Sex differences in mouse heart rate and body temperature and in their regulation by adenosine A1 receptors

Aim: To examine cardiac function, body temperature and locomotor behaviour in the awake adenosine A₁ receptor knock out mouse of both sexes. Methods: Male and female A₁R (+/+) and (−/−) mice, instrumented with telemetric devices, were recorded during basal conditions and after drug administration. Results: Female mice had higher heart rate, body temperature and locomotion, both during daytime and during the night. Awake A₁R (−/−) mice had a slightly elevated heart rate, and this was more clear‐cut in males. Heart rate was also higher in Langendorff‐perfused denervated A₁R (−/−) hearts. Body temperature was higher in A₁R (−/−) males and females; locomotor activity was higher in A₁R (−/−) females, but not in males. The adenosine receptor agonist R‐PIA (0.2 mg kg⁻¹) decreased heart rate and body temperature, but less in A₁R (−/−) animals than in A₁R (+/+) mice (P < 0.001 in both parameters). The unselective adenosine receptor antagonist caffeine had a minor stimulatory effect on heart rate in lower doses, but depressed it at a dose of 75 mg kg⁻¹. Body temperature was increased after a low dose (7.5 mg kg⁻¹) of caffeine in both sexes and genotypes, and markedly reduced after a high dose (75 mg kg⁻¹) of caffeine. An intermediary dose of caffeine 30 mg kg⁻¹ increased or decreased body temperature depending on genotype and sex. Locomotor responses to caffeine were variable depending both on genotype and sex. Conclusion: Thus, the adenosine A₁ receptor is involved in the regulation of heart rate, body temperature and locomotor activity, but the magnitude of the involvement is different in males and females.