Perinatal caffeine treatment: behavioral and biochemical effects in rats before weaning.
Administration of drinking water containing 0, 0.02%, 0.04% and 0.08% of caffeine to female rats throughout gestation and lactation affects several behavioral parameters in the offspring. Righting reflexes, swimming ability development, motor coordination and muscle tone were affected. The activity of these animals, as measured with an open-field test at weaning (i.e., at the end of the treatment), was reduced. The effects observed were dose-dependent. However, for righting reflexes the dose-dependency was direct (the highest dose producing maximal effects), whereas in all the other tests, the dose-dependency was inverse, the lowest dose producing maximal effects and the highest dose producing no effects. This might reflect the presence of subclasses of receptors having different affinities for adenosine, mediating opposite effects and antagonized by caffeine. On the other hand, perinatal caffeine effects are certainly not mediated by blockade of phosphodiesterases, since cAMP levels at the end of the treatment were dose-dependently reduced. This study shows therefore that administration of caffeine to rat dams is able to influence the neurobehavioral development of the offspring. Moreover, all the doses utilized and corresponding to 27, 58 and 108 mg/kg, were able to produce all or some of the mentioned effects, indicating that further testing with doses lower than 27 mg/kg is required to find a dose which does not affect the offspring.