Aim: 

The effects of the caffeine stimulation on adenosine A₁ and A_2A receptors (A₁-R and A_2A-R) and neuronal activation within the brainstem and hypothalamus during neurodevelopment would help to develop the hypothesis that there is an inhibitory role of A₁-R on respiration; whereas the role of A_2A-R becomes more important with age, implying a developmental change in the ratio of A₁/A_2A-R expression of the central cardio-respiratory areas.

Methods: 

Two groups of pups were fed by gavage on postnatal days P2-P6: water plus glucose and caffeine in therapeutical doses, which were sacrificed from P2 to P8. (Approved by the Animal Ethics Committee, 86/609/EEC).The presence of A₁ and A_2A-R and c-Fos protein was identified by means of immunohistochemical techniques.

Results: 

At P6 there was an increase in the density of A₁-R labelling in the caffeinated group in the parabrachial complex and the ventrolateral medulla; whereas the A_2A-R labelling in the parabrachial complex was moderate. An increase in the A₁ and A_2A-R labelling was found in the anterior hypothalamic area and ventromedial hypothalamic nucleus; whereas the A_2A-R labelling in the lateral hypothalamic area, the arcuate and periventricular nuclei was smaller. An increase in c-Fos⁺ distribution was found in the caffeinated group at the end of the treatment within the same areas; observing the highest increase in the arcuate nucleus.

Conclusion: 

The present results could improve the understanding of the clinical caffeine effects by the activation of gene expression in specific brain areas correlated with adenosine A₁ and A_2A-R expression at perinatal development.

Supported by PAI-BIO-183.