Changes in adrenoceptors and monoamine metabolism in neonatal and adult rat brain after postnatal exposure to the antihypertensive labetalol

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Abstract
1 The purpose of the present study was to investigate the acute (single injection), direct (chronic treatment) and the long-lasting effects after exposure to the α1/β-adrenoceptor antagonist labetalol during rat brain development on adrenoceptors and monoamine metabolism. 2 In 10-day-old rat pups, subcutaneously administered labetalol (10 mg kg−1) passed the blood-brain barrier, reaching a level of 2.1 μg g−1 tissue in the brain 90 min after injection. 3 Chronic labetalol treatment (10 mg kg−1, s.c., twice daily) during the first 10 days of life significantly increased α1-adrenoceptor binding in the hypothalamus (+39%), but not in the occipital cortex. 4 This chronic postnatal labetalol treatment did not result in long-lasting changes in α1 and β-receptors measured on day 60. 5 A single labetalol injection (10 mg kg−1, s.c.) on postnatal day 10 significantly increased noradrenaline (NA) metabolism in all brain regions tested (+25 to 105%), but had no effects on 5-hydroxytryptamine (5-HT) or dopamine metabolism. 6 Chronic labetalol treatment between postnatal (PN) days 1 and 10 also increased NA metabolism on PN 10 (3-methoxy-4-hydroxyphenylglycol (MHPG)/NA, +20 to 100%), suggesting that tolerance to the acute effect of labetalol did not occur. A slight increase in 5-HT metabolism (20%) was induced by the chronic labetalol treatment in the hippocampus and meso-limbic system. 7 In general, long-lasting effects on NA metabolism could not be detected on day 60, more than one month after the treatment. However, 5-HT metabolism was significantly increased in all four brain regions measured (+20 to 70%). 8 We conclude that chronic labetalol exposure during early postnatal rat brain development does not cause long-lasting changes in β-receptor number or NA metabolism, but appears to be critical for the rate of 5-HT metabolism in later life.