Effects of Early Life Exposure to Sex Hormones on Neurochemical and Behavioral Responses to Psychostimulants in Adulthood: Implications in Drug Addiction (original) (raw)
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Journal of neuroendocrinology, 2018
Steroid sex hormones produce physiological effects in reproductive tissues and also in non-reproductive tissues such as the brain, particularly in cortical, limbic and midbrain areas. Dopamine (DA) neurons involved in processes such as prolactin secretion (tuberoinfundibular system), motor circuit regulation (nigrostriatal system) and driving of motivated behavior (mesocorticolimbic system), are specially regulated by sex hormones. Indeed, sex hormones promote neurochemical and behavioral effects induced by drugs of abuse by tuning midbrain DA neurons in adult animals. However, the long-term effects induced by neonatal exposure to sex hormones on dopaminergic neurotransmission have not been fully studied. The focus of this work was to reveal if a single neonatal exposure with estradiol valerate (EV) results in a programming of dopaminergic neurotransmission in the nucleus accumbens (NAcc) of adult female rats. To answer this question, electrophysiological, neurochemical, cellular, m...
Sex Hormones and Brain Dopamine Functions
Central Nervous System Agents in Medicinal Chemistry, 2015
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 the limbic and midbrain areas.
Frontiers in Pharmacology
Neonatal programming with sex hormones produces long-term functional changes in various tissues, including the brain. Previously, we demonstrated a higher content of dopamine and an increase in potassium-induced dopamine release in the nucleus accumbens of adult rats exposed to estradiol valerate. On the other hand, sex hormones also affect the opioid system increasing the expression of the µ opioid receptor and β-endorphins. Here, we investigated if neonatal programming with sex hormones alters the response to morphine during adulthood in rats and predispose them to neurochemical, rewarding and behavioral activating effects. We examined the effects of neonatal exposure to a single dose of estradiol valerate or testosterone propionate on morphine-induced (5 mg/kg, i.v.) dopamine release in the nucleus accumbens and morphine-induced (3 mg/kg, s.c.) locomotor activity and conditioned place preference when these rats were adults. Our results showed a significant increase in morphineinduced dopamine release in the nucleus accumbens of rats that were exposed neonatally to estradiol compared with control rats. This effect was correlated with higher place preference and locomotor activity induced by morphine in adult rats neonatally exposed to estradiol valerate. However, the effect of morphine on dopamine release and behaviors was similar in rats treated with testosterone compared to control rats. Additionally, the expression of mu (µ) opioid receptor, dopamine receptor type 1 (D 1) and dopamine receptor type 2 (D 2) in the nucleus accumbens of adult rats was not different after treatment with sex hormones. Taken together, our results demonstrated
Hormonal contraceptives alter amphetamine place preference and responsivity in the intact female rat
bioRxiv, 2021
Hormonal contraceptives (HCs) are commonly used among reproductive aged women and alter the physiological state of the user by interfering with endogenous hormone concentrations and their actions on the reproductive tract. As hormones such as estradiol and progesterone modulate the incidence of substance abuse disorders in women, it is important to consider the influence HCs have on the female brain and behavior. This experiment explores how female sex steroid hormonal states associated with the rat estrous cycle, and modulating those states with HCs, influences measures of drug preference and responsivity. First, rats underwent food-light Pavlovian conditioning to measure conditioned orienting, a known predictor of amphetamine (AMP) place preference. Then, rats were conditioned and tested for AMP place preference with either an HC-implant or during estrous cycle stages associated with different ovarian hormone levels (i.e., proestrus (P) or metestrus/diestrus (M/D) while recording ...
Neural Plasticity, 2016
We sought to determine the long-term changes produced by neonatal sex hormone administration on the functioning of midbrain dopaminergic neurons in adult male rats. Sprague-Dawley rats were injected subcutaneously at postnatal day 1 and were assigned to the following experimental groups: TP (testosterone propionate of 1.0 mg/50 μL); DHT (dihydrotestosterone of 1.0 mg/50 μL); EV (estradiol valerate of 0.1 mg/50 μL); and control (sesame oil of 50 μL). At postnatal day 60, neurochemical studies were performed to determine dopamine content in substantia nigra-ventral tegmental area and dopamine release in nucleus accumbens. Molecular (mRNA expression of tyrosine hydroxylase) and cellular (tyrosine hydroxylase immunoreactivity) studies were also performed. We found increased dopamine content in substantia nigra-ventral tegmental area of TP and EV rats, in addition to increased dopamine release in nucleus accumbens. However, neonatal exposure to DHT, a nonaromatizable androgen, did not af...
Pharmacology Biochemistry and Behavior, 1994
Influence of the estrous cycle and estradiol on the behavioral effects of amphetamine and apomorphine in rats. PHARMACOL BIOCHEM BEHAV 49(4) [819][820][821][822][823][824][825] 1994.-This experiment was designed to investigate the influence of hormonal status of the rat on the effects of two doses of an indirect-acting dopamine agonist (amphetamine 0.25 and 1.0 mg/kg, IP) and a direct-acting dopamine agonist (apomorphine 62.5 and 250 #g/kg, SC) on the acquisition of conditioning avoidance responses (CARs) and the performance of some spontaneous behaviors. Active conditioned avoidance was improved by amphetamine in all the groups except in females at diestrus; apomorphine improved this response only in females at estrus and in ovariectomized rats after estradiol replacement, but the avoidance response was deteriorated in males and females at diestrus and after ovariectomy without estradiol replacement. Both dopaminergic drugs had contrasting effects on motor activity, number of rearings, and number of head shakes according to the hormonal status of the rat. Only the time spent in grooming behavior decreased after the treatment with both dopamine agonists in all of the five groups studied. These results provided behavioral evidence for the hypothesis that dopaminergic activity in the CNS is affected distinctively by modifications in the sexual hormone status (gender, estrous cycle, ovariectomy, and estradiol replacement). Relationships between ovarian hormones and dopaminergic system are discussed.
Pharmacology Biochemistry and Behavior, 1999
BECKER, J. B. AND C. N. RUDICK. Rapid effects of estrogen or progesterone on the amphetamine-induced increase in striatal dopamine are enhanced by estrogen priming: A microdialysis study. PHARMACOL BIOCHEM BEHAV 64 (1) [53][54][55][56][57] 1999.-There are estrous cycle-dependent differences in amphetamine-stimulated behaviors and striatal dopamine (DA) release; intact female rats exhibit a greater behavioral response to amphetamine on estrus than on other days of the cycle. Following ovariectomy amphetamine-induced behavior is attenuated, as is the striatal DA response to amphetamine in vitro. Repeated estrogen treatment in ovariectomized rats reinstates both of these responses to a level comparable to estrous females. In addition, 30 min after a single treatment with a physiological dose of estrogen there is enhanced amphetamineinduced behavior and increased amphetamine-induced striatal DA detected during microdialysis. This experiment was conducted to determine whether the acute effect of estradiol and the effect of repeated exposure to estrogen are functionally related. We report here that prior treatment with estrogen (three daily treatments of 5 g estradiol benzoate) results in a significant enhancement of the effect of acute estrogen (5 g estradiol benzoate) or progesterone (500 g) on amphetamineinduced striatal DA release and stereotyped behaviors. Both the peak response and the duration of the response are greater in estrogen-primed animals treated with estrogen or progesterone 30 min prior to amphetamine, than in all other groups. Either prior treatment with estrogen (last dose 24 h before) or a single acute injection of estrogen result in an enhanced peak response to amphetamine, with no effect on the duration of amphetamine-induced striatal DA release. Treatment with progesterone in animals not primed with estrogen was not different from treatment with oil vehicle. These results demonstrate that there are both acute and long-term effects of estrogen on the striatum that underlie the dynamic changes in stimulated DA release and amphetamine-induced behaviors during the reproductive cycle. © 1999 Elsevier Science Inc.
The emergence of gonadal hormone influences on dopaminergic function during puberty
Hormones and Behavior, 2010
Adolescence is the developmental epoch during which children become adults-intellectually, physically, hormonally and socially. Brain development in critical areas is ongoing. Adolescents are risk-taking and novelty-seeking and they weigh positive experiences more heavily and negative experiences less than adults. This inherent behavioral bias can lead to risky behaviors like drug taking. Most drug addictions start during adolescence and early drug-taking is associated with an increased rate of drug abuse and dependence.
Hormones and Behavior, 2007
Estrogen enhances dopamine-mediated behaviors, which make women and female rats more sensitive to the effects of the psychostimulant drugs, cocaine and amphetamine. How cocaine and amphetamine elicit more robust behavioral responses in females remains unclear, but studies have shown that the Regulator of G-protein Signaling 9-2 (RGS9-2) protein is an important modulator of the behavioral responses to these drugs. Previously, we reported that 17-beta estradiol reduced RGS9-2 mRNA expression in the shell of the nucleus accumbens, but not the core. The present studies were designed to further evaluate the involvement of RGS9-2 in estradiol enhancement of amphetamine-induced place preference behavior and to examine which estrogen receptor subtype mediates the effect of estradiol. Female Sprague-Dawley rats were ovariectomized and treated for 14 days with an inert vehicle or 17-beta estradiol (by Silastic implant or injection [80 μg/kg]). 17-β-Estradiol-treated female rats had enhanced amphetamine-induced conditioned place preference behavior compared to vehicle-treated, ovariectomized female rats. In situ hybridization histochemistry and Western blotting identified an inverse relationship between RGS9-2 protein expression in the nucleus accumbens shell and the hormonal enhancement of amphetamine-induced place preference behavior. A similar relationship was not found between place preference behavior and RGS9-2 expression in the accumbens core. Moreover, treatment of ovariectomized female rats with the selective estrogen receptor-beta agonist, diarylpropionitrile (1 mg/kg), for 2 weeks also facilitated amphetamine-induced place preference behavior and selectively reduced nucleus accumbens shell RGS9-2 protein expression. These data provide insight into a potential mechanism by which estrogen and/or sex modulate mesoaccumbal dopamine receptor signaling and possibly, addictive behaviors. Published by Elsevier Inc.
Prenatal Amphetamine Exposure Effects on Dopaminergic Receptors and Transporter in Postnatal Rats
Neurochemical Research, 2011
We investigated the influence of prenatal amphetamine exposure (PAE) on dopamine (DA) receptors, and dopamine transporter (DAT) in various striatal and limbic subregions and locomotor activity induced by novel environmental conditions and amphetamine at two postnatal ages, 35 days old (prepubertal) and 60 days old (postpubertal). Experiments were carried out on pregnant female Sprague-Dawley rats, which were daily injected with either d-amphetamine sulfate (1 mg/kg) or saline solution (0.9%) for 11 days, from gestation day 11-21. In PAE rats compared to control we found the following: at pre-pubertal age, an enhancement of DA D1 in the dorsolateral area of the caudate-putamen (CPu), CPu-ventral and shell of the nucleus accumbens (NAcc) with a decrement of the DA D3 receptors in NAcc, olfactory tubercle (OT), and the islands of Calleja (IoC); whereas at postpubertal age, an increase in the levels of DAT in the NAcc and fundus of the CPu, and OT along with a decrease in the expression of DA D2 receptors only in the NAcc shell were found in PAE rats compared to control. In addition, amphetamine induces a marked decrease in locomotor activity at postpubertal age in rats with PAE. These results suggest a differential effect of amphetamines on the DAT mechanism of the nervous system during embryonic development of animals with implications in behavior and drug addictions at adulthood age.