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

Br J Pharmacol. 1992 Jan;105(1):37-44. doi: 10.1111/j.1476-5381.1992.tb14207.x.

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 alpha 1/beta-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 micrograms 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 alpha 1-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 alpha 1- and beta-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 beta-receptor number or NA metabolism, but appears to be critical for the rate of 5-HT metabolism in later life.

MeSH terms

  • Animals
  • Animals, Newborn / metabolism*
  • Biogenic Amines / metabolism*
  • Body Weight / drug effects
  • Brain / drug effects*
  • Brain / growth & development
  • Brain / metabolism
  • Labetalol / pharmacology*
  • Organ Size / drug effects
  • Propranolol / pharmacology
  • Rats
  • Rats, Inbred Strains
  • Receptors, Adrenergic / drug effects*
  • Receptors, Adrenergic / metabolism

Substances

  • Biogenic Amines
  • Receptors, Adrenergic
  • Propranolol
  • Labetalol