REGULATION OF RAT-BRAIN VESICULAR MONOAMINE TRANSPORTER BY CHRONIC TREATMENT WITH OVARIAN HORMONES

Ovarian steroids play an important role in neuroregulation and in the pathophysiology of various neuropsychiatric disorders. Most of the stu dies focused on the impact of gonadal steroids on post-synaptic recept ors and plasma membrane transporters. In the present study, we evaluat ed the effect of chronic treatment with ovarian steroids on the expres sion of rat brain vesicular monoamine transporter (VMAT(2)). Ovariecto mized rats were treated for 21 days with estradiol, progesterone or bo th. VMAT(2) gene expression was assessed on the protein level by high affinity [H-3]dihydrotetrabenazine ([H-3]TBZOH) binding using autoradi ography and on the mRNA level by in situ hybridization. Progesterone a dministration led to a decrease in [H-3]TBZOH binding in the middle st riatum and in the nucleus accumbens and to a parallel decrease in VMAT (2) mRNA level in the substantia nigra pars compacts and dorsal raphe nuclei. Chronic estradiol treatment reduced VMAT(2) mRNA level in the dorsal raphe and [H-3]TBZOH binding in middle part of the striatum and nucleus accumbens but did not affect VMAT(2) mRNA level in the substa ntia nigra pars compacta. Simultaneous administration of both ovarian steroids did not modulate VMAT(2) mRNA in the substantia nigra pars co mpacta as well as [H-3]TBZOH binding in the striatum or the nucleus ac cumbens but reduced VMAT(2) mRNA level in the dorsal raphe. It appears that ovarian steroids may play a crucial role in the regulation of VM AT(2) gene expression in the dopamine and serotonin systems. This modu latory activity may be relevant to synaptic and neuronal plasticity as well as to the molecular and cellular pathophysiology of gender-speci fic neuropsychiatric disorders. (C) 1998 Elsevier Science B.V. All rig hts reserved.