POSTNATAL EXPOSURE TO THE BETA-ADRENOCEPTOR AGONIST CLENBUTEROL HAS REGIONALLY SELECTIVE DIRECT AND LONG-TERM EFFECTS ON RAT-BRAIN BETA-ADRENOCEPTORS AND MONOAMINE METABOLISM

The effects of chronic postnatal beta2-adrenoceptor activation on the maturation of the rat brain noradrenergic system have been studied. For that purpose, rat pups have been treated twice daily during the first 10 days of life with the beta2-agonist clenbuterol-HCl (2.5 mg/kg s.c.), and the effects on the beta-adrenoceptor number and monoamine metabolism have been determined directly after the treatment and in adulthood. On postnatal day 10, 90 min after the last clenbuterol injection 4.5 mug/g of the drug was present in the brain. At the end of the treatment the beta-receptor binding had decreased in the cerebellum (35%), but not in the frontal cortex or mesolimbic system. Clenbuterol significantly increased the steady-state brain levels of noradrenaline (NA) in the striatum 90 min after the last injection, whereas the levels in the frontal cortex, meso-limbic system, medulla pons and cerebellum were unaffected. The NA metabolite 3-methoxy-4-hydroxyphenylglycol (MHPG), had significantly increased in the frontal cortex and striatum. The serotonergic (5-HT) and dopaminergic (DA) system were not altered. In general, no long-lasting effects on beta-adrenoceptor number and affinity or monoamine metabolism were measurable, except for the frontal cortex which showed a sustained increase of MHPG, a decrease of 5-HT and an increase of 5-HIAA/5-HT on PN 60. In conclusion, chronic postnatal activation of beta2-adrenoceptors by clenbuterol treatment selectively causes changes in the setting of the neurochemical parameters investigated in the frontal cortex.