Opposite modulatory effects of ovarian hormones on rat brain dopamine and serotonin transporters
ABSTRACT 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.
SourceAvailable from: Ramón Sotomayor-Zárate[Show abstract] [Hide abstract]
ABSTRACT: Sex hormones exert differential effects on a variety of sensitive tissues like the reproductive tract, gonads, liver, bone and adipose tissue, among others. In the brain, sex hormones act as neuroactive steroids regulating the function of neuroendocrine diencephalic structures like the hypothalamus. In addition, steroids can exert physiological effects upon cortical, limbic and midbrain structures, influencing different behaviors such as memory, learning, mood and reward. In the last three decades, the role of sex hormones on monoamine neurotransmitters in extra-hypothalamic areas related to motivated behaviors, learning and locomotion has been the focus of much research. The purpose of this thematic issue is to present the state of art concerning the effects of sex hormones on the neurochemical regulation of dopaminergic midbrain areas involved in neurobiological and pathological processes, such as addiction to drugs of abuse. We also discuss evidence of how neonatal exposure to sex hormones or endocrine disrupting chemicals can produce long-term changes on the neurochemical regulation of dopaminergic neurons in limbic and midbrain areas.Central Nervous System Agents in Medicinal Chemistry(Formerly Current Medicinal Chemistry - Central Nervous System Agents) 12/2014; 14(2). DOI:10.2174/1871524914666141226105137
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ABSTRACT: Women and female rodents are more responsive to the subjective effects of psychostimulant drugs of abuse compared to males. A growing body of literature supports a role for estradiol as a mechanism underlying these sex differences. However, little is known about the influence of acute elevations in levels of estradiol on drug conditioned behaviors. The aim of the present study was to evaluate the influence of an acute increase in systemic estradiol levels on the expression of cocaine conditioned place preference (CPP). Using a six day conditioning procedure, ovariectomized (OVX) female rats were conditioned with one of four doses of cocaine (2.5, 5, 10, or 15 mg/kg) to associate one of two large chambers of a CPP apparatus with cocaine or saline. Thirty minutes prior to the start of the CPP preference test, rats were pretreated with either 5 μg estradiol benzoate (EB) or peanut oil (PO). PO-treated rats expressed a significant preference for only the mid-range conditioning doses of cocaine (5 and 10 mg/kg). However, acute EB treatment resulted in a rightward shift in the cocaine dose-response curve; rats demonstrated a significant preference at only the moderate and high conditioning doses of cocaine (10 and 15 mg/kg). These findings demonstrate that acute elevations in estradiol may dampen the expression of conditioned responses to cocaine's secondary rewards at lower conditioning doses of the drug and facilitate CPP at higher doses while estradiol deficiency decreases the threshold dose of cocaine necessary to induce CPP.Brain research bulletin 04/2014; 103. DOI:10.1016/j.brainresbull.2014.02.002 · 2.97 Impact Factor
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ABSTRACT: Progesterone is a steroid which regulates neural function, thereby modulating neurotransmission, cell survival, and behavior. Previous studies by our group have shown that chronic administration of low doses of progesterone in diestrus II female rats has an antidepressant-like effect in the forced swimming test (FST). Depression is associated with the several neurotransmitters systems, including GABA and serotonin, and with neurodegeneration and cell death in some brain circuits. The aim of this study was to verify the effect of progesterone on the protein expression of the GABA(A) receptor α4 subunit, serotonin transporter (SERT), Akt, extracellular signal-regulated kinase (Erk), and caspase-3 in the hypothalamus of diestrus II female rats exposed to the FST. Female rats were treated with a daily injection of progesterone (0.4 mg/kg) or vehicle, during two complete oestrous cycles. On the day of the experiment, the animals were euthanized 30 min after the FST, the hypothalamus was dissected and protein expression of GABA(A) receptor α4 subunit, SERT, Akt, Erk, and caspase-3 was evaluated. Progesterone increased the expression of GABA(A) receptor α4 subunit but did not change the expression of SERT. Progesterone decreased the expression of procaspase-3 in the hypothalamus without changing the activation of Akt and Erk in this structure. In summary, our results suggest that progesterone acts to increase the expression of the GABA(A) receptor α4 subunit and decrease the expression of procaspase-3 in the hypothalamus of female rats. Such effects may be involved in the antidepressant-like effect of progesterone in female rats exposed to the FST.Endocrine 12/2013; 46(3). DOI:10.1007/s12020-013-0126-5 · 3.53 Impact Factor