Increasedα2-adrenoceptor mediated regulation of adult rat brain noradrenaline overflow after chronic neonatal exposure to propranolol; a microdialysis study

Abstract Direct and persistent effects of chronic neonatal administration of the β-adrenoceptor antagonist propranolol on brain noradrenergic activity were investigated by measuring tissue concentrations of noradrenaline and its metabolites and in vivo overflow of noradrenaline during adulthood. Rat pups were chronically treated with propranolol from postnatal day 1 to day 10. Determination of monoamine metabolism after the last injection showed an increase in noradrenaline metabolism in frontal cortex, limbic system and hippocampus of propranolol-exposed rats, but 47 days after this last injection it was apparent that these effects were not long-lasting. Moreover, basal noradrenaline overflow in vivo in the hippocampus of 40–55 day-old propranolol-exposed rats did not differ from that in controls. However, the regulation of noradrenaline release seemed to have been altered, since a pharmacological challenge with theα 2 -adrenoceptor antagonist idazoxan induced an enhanced increase in the in vivo noradrenaline overflow in propranolol-exposed rats compared to controls. It is suggested that the neonatal β-blockade induced a supersensitivity of the presynapticα 2 -adrenoceptor. The precise mechanism underlying this effect has to be elucidated.