Opposite modulatory effects of ovarian hormones on rat brain dopamine and serotonin transporters.
The present study was designed to investigate the modulatory effect of gonadal steroids on brain dopamine (DA) and serotonin (5-HT) presynaptic transporters in female and male rats. Female and male rats were castrated and treated with either vehicle or gonadal hormones. The pharmacodynamic characteristics of the DA and 5-HT transporters were analyzed by [3H]BTCP and [3H]imipramine binding respectively. Ovariectomy (OVX) resulted in an upregulation of the striatal DA transporter and this alteration was prevented by estradiol (E2) or E2 + progesterone (P) treatment but not by P alone. In contrast to the DA transporter, the hypothalamic 5-HT transporter was down-regulated by OVX in female rats and this decrease was reversed by the administration of E2, P or their combination. The striatal DA transporter and the hypothalamic 5-HT transporter in male rat were not affected by orchidectomy or by administration of testicular hormone. Our findings indicate that ovarian, but not testicular, steroid hormones may play an important role in the regulation of brain DA and 5-HT transporters. It appears that ovarian hormones modulate rat brain 5-HT and DA transporters in opposite directions. These interactions between ovarian steroids and presynaptic transporters may be relevant to DA- and 5-HT-related neuropsychiatric disorders.
Attali
G
G
Department of Physiology and Pharmacology, Sackler Faculty of Medicine, Tel-Aviv University, Israel.
Weizman
A
A
Gil-Ad
I
I
Rehavi
M
M
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism*; D018491:Dopamine Agonists / Q000378:metabolism; D050483:Dopamine Plasma Membrane Transport Proteins; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D007099:Imipramine / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D010052:Ovariectomy; D010622:Phencyclidine / Q000031:analogs & derivatives / Q000378:metabolism; D011374:Progesterone / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D050486:Serotonin Plasma Membrane Transport Proteins
D002352:Carrier Proteins; D018491:Dopamine Agonists; D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D050486:Serotonin Plasma Membrane Transport Proteins; C493232:Slc6a4 protein, rat; C056415:1-(1-(2-benzo(b)thienyl)cyclohexyl)piperidine; D011374:Progesterone; D004958:Estradiol; D010622:Phencyclidine; D007099:Imipramine