Effects of neonatal exposure to caffeine on adenosine A1 receptor ontogeny using autoradiography

The ontogeny of adenosine A1 receptor density was assessed via autoradiographical analysis of [3H]cyclohexyladenosine ([3H]CHA) binding in brains of 14-31-day-old rats as a function of exposure to caffeine over postnatal days 2-6. This exposure period was analogous to the period during which human infants are administered caffeine as treatment for apnea of prematurity. [3H]CHA binding was greatest in CA1 and CA3 hippocampus in both caffeine-exposed and control rats across all ages. Within the anterior, ventral, lateral and medial regions of the thalamus of unmanipulated rats, [3H]CHA binding did not change with age. In caffeine-exposed rats, however, [3H]CHA binding increased significantly within these thalamic subregions as the rats aged. In addition, with age in both treatment groups, the molecular and granular layers of the cerebellum and the CA1 and dentate gyrus of the hippocampus displayed increasing [3H]CHA density. Furthermore, regardless of age, [3H]CHA binding was decreased in the molecular layer of neonatally caffeine-exposed animals as compared to controls. Thus, limited exposure to caffeine within the first postnatal week altered the subsequent expression of adenosine A1 receptors in most subregions of the thalamus and in the molecular layer of the cerebellum.