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 studies focused on the impact of gonadal steroids on post-synaptic receptors and plasma membrane transporters. In the present study, we evaluated the effect of chronic treatment with ovarian steroids on the expression of rat brain vesicular monoamine transporter (VMAT 2). Ovariectomized rats were treated for 21 days with estradiol, progesterone or both. VMAT 2 gene expression was assessed on the protein level by high affinity [ 3 H] dihydrotetrabenazine ( [ 3 H] TBZOH) binding using autoradiography and on the mRNA level by in situ hybridization. Progesterone administration led to a decrease in [ 3 H] TBZOH binding in the middle striatum and in the nucleus accumbens and to a parallel decrease in VMAT 2 mRNA level in the substantia nigra pars compacta and dorsal raphè nuclei. Chronic estradiol treatment reduced VMAT 2 mRNA level in the dorsal raphè and [ 3 H] TBZOH binding in middle part of the striatum and nucleus accumbens but did not affect VMAT 2 mRNA level in the substantia nigra pars compacta. Simultaneous administration of both ovarian steroids did not modulate VMAT 2 mRNA in the substantia nigra pars compacta as well as [ 3 H] TBZOH binding in the striatum or the nucleus accumbens but reduced VMAT 2 mRNA level in the dorsal raphè. It appears that ovarian steroids may play a crucial role in the regulation of VMAT 2 gene expression in the dopamine and serotonin systems. This modulatory activity may be relevant to synaptic and neuronal plasticity as well as to the molecular and cellular pathophysiology of gender-specific neuropsychiatric disorders.