Gender, Estrous Cycle, Ovariectomy, and Ovarian Hormones Influence the Effects of Diazepam on Avoidance Conditioning in Rats

Dı́az-Véliz, Gabriela; Butrón, Sebastian; Benavides, M.Soledad; Dussaubat, Nelson; Mora, Sergio

doi:10.1016/s0091-3057(00)00283-5

Cited by 53 publications

(34 citation statements)

References 17 publications

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“…Our findings provide compelling evidence for a neurofunctional effect of the menstrual cycle on the human reward system, and they bring important new sources of information to bear on previous findings in rodents demonstrating interactions between dopamine and female gonadal steroid hormones (12,13). It is interesting to note that, from an evolutionary perspective, the increased availability, receptivity, and desire that may occur during the ovulatory period has been thought to facilitate procreation.…”

Section: Discussionsupporting

confidence: 64%

“…The facts that female rats show the highest rates of cocaine self-administration shortly after estradiol peaks and that estradiol administration to ovariectomized females enhances the acquisition of cocaine self-administration (10, 11) also offer evidence for estrogenic modulation of the rodent reward system. Conversely, systemic administration of dopamine agonists and antagonists modulates conditioned and spontaneous behavior according to sex, estrous cycle, ovariectomy, and estrogen administration (12,13). These effects could be due, at least in part, to dopamine activation of a number of steroid receptors, including progesterone receptors, by a ligand-independent mechanism (14)(15)(16).…”

mentioning

confidence: 99%

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Menstrual cycle phase modulates reward-related neural function in women

Dreher

Schmidt

Kohn

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

488

365

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There is considerable evidence from animal studies that the mesolimbic and mesocortical dopamine systems are sensitive to circulating gonadal steroid hormones. Less is known about the influence of estrogen and progesterone on the human reward system. To investigate this directly, we used functional MRI and an event-related monetary reward paradigm to study women with a repeated-measures, counterbalanced design across the menstrual cycle. Here we show that during the midfollicular phase (days 4 -8 after onset of menses) women anticipating uncertain rewards activated the orbitofrontal cortex and amygdala more than during the luteal phase (6 -10 days after luteinizing hormone surge). At the time of reward delivery, women in the follicular phase activated the midbrain, striatum, and left fronto-polar cortex more than during the luteal phase. These data demonstrate augmented reactivity of the reward system in women during the midfollicular phase when estrogen is unopposed by progesterone. Moreover, investigation of between-sex differences revealed that men activated ventral putamen more than women during anticipation of uncertain rewards, whereas women more strongly activated the anterior medial prefrontal cortex at the time of reward delivery. Correlation between brain activity and gonadal steroid levels also revealed that the amygdalo-hippocampal complex was positively correlated with estradiol level, regardless of menstrual cycle phase. Together, our findings provide evidence of neurofunctional modulation of the reward system by gonadal steroid hormones in humans and establish a neurobiological foundation for understanding their impact on vulnerability to drug abuse, neuropsychiatric diseases with differential expression across males and females, and hormonally mediated mood disorders. B ehavioral, biochemical, and physiological data in animals demonstrate that the gonadal steroid hormones estrogen and progesterone affect behavior and modulate neuronal activity (1-4). These hormones not only influence ovulation and reproductive behavior but also affect cognitive functions, affective state, vulnerability to drugs of abuse, and pain sensitivity. Although ovarian steroids have widespread neurophysiological effects, including on the dopaminergic system, and although estrogen and progesterone receptors are densely present along midbrain dopaminergic neurons and other components of the reward system (such as the amygdala and striatum), little is known about the influences of estrogen and progesterone on the dopamine-dependent reward system in women.Substantial preclinical data, including behavioral and neurochemical differences between sexes, across the estrous cycle, and in postovariectomy hormone replacement (5, 6), attest to neuroregulatory effects of both estrogen and progesterone on the dopaminergic system (7, 8), not only on the tuberoinfundibular dopaminergic system involved in control of the anterior pituitary and important for ovulation and reproductive behavior, but also on the mesolimbic and mesocortical dopa...

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Section: Discussionsupporting

confidence: 64%

mentioning

confidence: 99%

Menstrual cycle phase modulates reward-related neural function in women

Dreher

Schmidt

Kohn

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

488

365

View full text Add to dashboard Cite

show abstract

“…Effects of hormones on conditioning were originally proposed by one of the pioneering researchers in Behavioral Endocrinology, Frank Beach, when he was mentored by Karl Lashley, an eminent investigator in learning and memory (Beach, 1937). During behavioral estrus (proestrus), when rats are most receptive to mating, acquisition of conditioned avoidance responses is reduced compared to on diestrous (Diaz-Veliz et al, 2000), which may enable aversive aspects of mating to be tolerated. Environmental stimuli associated with mating, when E 2 and progestin levels are elevated, readily become conditioned stimuli (Domjan, 2005).…”

Section: Progestins Estrogen and Conditioningmentioning

confidence: 99%

Progestins influence motivation, reward, conditioning, stress, and/or response to drugs of abuse

Frye

2007

Pharmacology Biochemistry and Behavior

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Progesterone (pregn-4-ene-3,20-dione; P) and its metabolite 5α-pregnan-3α-ol-20-one (3α,5α-THP) are secreted by ovaries, adrenals, and glial cells. 3α,5α-THP in the midbrain ventral tegmental area mediates sexual receptivity of rodents through its actions at GABA A , NMDA, and/ or D 1 receptors. The extent to which 3α,5α-THP may influence anti-anxiety/anti-stress effects, conditioning and/or reward through these substrates and/or by altering hypothalamic pituitary adrenal axis function is discussed. Biosynthesis of 3α,5α-THP occurs in responses to mating and may underlie some of the rewarding aspects of sexual behavior. Recent findings from our laboratory which demonstrate that progestins can enhance approach to novel stimuli, conditioning, and reinforcement are reviewed. How progestins' effects on these processes may underlie response to drugs of abuse is considered and new findings which demonstrate interactions between progestins and cocaine are presented.

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“…Exploration, anti-anxiety, and pro-social behaviors of female rodents are increased during behavioral estrus, when E 2 and 3α,5α-THP levels are high, relative to other phases of the estrous cycle [13][14][15][16][17]. Increasing levels of 3α,5α-THP in brain enhances exploratory, anti-anxiety, and social behaviors.…”

Section: Introductionmentioning

confidence: 98%

Infusions of 3α,5α-THP to the VTA enhance exploratory, anti-anxiety, social, and sexual behavior and increase levels of 3α,5α-THP in midbrain, hippocampus, diencephalon, and cortex of female rats

Frye

Rhodes

2008

Behavioural Brain Research

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Abstract17β-Estradiol (E 2 ) and progesterone (P 4 ) influence the onset and duration of sexual behavior and are also associated with changes in behaviors that may contribute to mating, such as exploration, anxiety, and social behaviors (socio-sexual behaviors). In the midbrain ventral tegmental area (VTA), the P 4 metabolite, 5α-pregnan-3α-ol-20-one (3α,5α-THP), modulates lordosis of E 2 -primed rodents; 3α,5α-THP can also influence anxiety and social behaviors. To examine if 3α,5α-THP in the VTA mediates socio-sexual behaviors, we infused 3α,5α-THP to the VTA of diestrous and proestrous rats. As expected, proestrous, compared to diestrous, rats showed more exploratory (open field), anxiolytic (elevated plus maze), pro-social (partner preference, social interaction), and sexual (paced mating) behavior and had increased E 2 , P 4 , dihydroprogesterone (DHP), and 3α,5α-THP in serum, midbrain, hippocampus, diencephalon, and cortex. Infusions of 3α,5α-THP to the VTA, but not control sites, such as the substantia nigra (SN) or central grey (CG), of diestrous rats produced behavioral and endocrine effects akin to that of proestrous rats and increased DHP and 3α,5α-THP levels in midbrain, hippocampus, and diencephalon. Levels of DHP and 3α,5α-THP, but neither E 2 nor P 4 concentrations, in midbrain, hippocampus, diencephalon, and/or cortex were positively correlated with socio-sexual behaviors. Thus, 3α,5α-THP infusions to the VTA, but not SN or CG, can enhance socio-sexual behaviors and increase levels in midbrain, hippocampus, and diencephalon.

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Gender, Estrous Cycle, Ovariectomy, and Ovarian Hormones Influence the Effects of Diazepam on Avoidance Conditioning in Rats

Cited by 53 publications

References 17 publications

Menstrual cycle phase modulates reward-related neural function in women

Menstrual cycle phase modulates reward-related neural function in women

Progestins influence motivation, reward, conditioning, stress, and/or response to drugs of abuse

Infusions of 3α,5α-THP to the VTA enhance exploratory, anti-anxiety, social, and sexual behavior and increase levels of 3α,5α-THP in midbrain, hippocampus, diencephalon, and cortex of female rats

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