Behavioral effects of endogenous or exogenous estradiol and progesterone on cocaine sensitization in female rats

Souza, Marilise Fraga de; Couto-Pereira, Natividade S.; Freese, Luana; Costa, Priscila A.; Caletti, Greice; Bisognin, K. M.; Nin, Maurício Schüler; Gomez, Rosane; Barros, Helena M.T.

doi:10.1590/1414-431x20143627

Cited by 26 publications

(13 citation statements)

References 38 publications

(74 reference statements)

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“…Although this interpretation is somewhat complicated because a rise in estradiol also occurs in the luteal phase, there is preclinical research with ovariectomized rats showing that exogenous progesterone administration can undo the liabilities posed by exogenous estradiol. [58][59][60][61] This line of research suggests that when both hormones are present, it is likely the case that progesterone dominates.…”

Section: Discussionmentioning

confidence: 99%

Increasing Progesterone Levels Are Associated With Smoking Abstinence Among Free-Cycling Women Smokers Who Receive Brief Pharmacotherapy

Saladin

McClure

Baker

et al. 2015

Nicotine & Tobacco Research

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Introduction: Preclinical and human laboratory research suggests that (a) progesterone may decrease drug reward, craving, and smoking behavior, and (b) estradiol may enhance drug reward and smoking behavior. A modest majority of treatment research examining the relationship between menstrual cycle phase and outcomes suggests that the luteal menstrual phase, with its uniquely higher progesterone levels, is associated with better cessation outcomes. However, no studies to date have examined the effects of naturally occurring variation in progesterone and estradiol levels on medication-assisted smoking cessation. The present study sought to fill this notable gap in the treatment literature. Methods: Weekly plasma progesterone and estradiol levels were obtained from nicotine-dependent female smokers enrolled in a 4-week cessation trial. Participants (N = 108) were randomized to receive a 4-week course of either varenicline (VAR) tablets and placebo patches or placebo tablets and nicotine patches. Plasma samples were obtained 1 week before their cessation attempt and weekly during medication administration. Abstinence was assessed weekly. Results: Weekly hormone data replicated commonly observed menstrual cycle patterns of progesterone and estradiol levels. Importantly, increases in progesterone level were associated with a 23% increase in the odds for being abstinent within each week of treatment. This effect was driven primarily by nicotine patch-treated versus VAR-treated females. Conclusions: This study was the first to identify an association between progesterone level (increasing) and abstinence outcomes in free-cycling women smokers who participated in a medicationbased treatment. Furthermore, the potential benefits of progesterone may vary across different pharmacotherapies. Implications of these findings for smoking cessation intervention are discussed.

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Section: Discussionmentioning

confidence: 99%

Increasing Progesterone Levels Are Associated With Smoking Abstinence Among Free-Cycling Women Smokers Who Receive Brief Pharmacotherapy

Saladin

McClure

Baker

et al. 2015

Nicotine & Tobacco Research

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“…In humans, exogenous administration of PRO attenuated cocaine use and relapse to cocaine (Yonkers et al, 2014). In rodents, PRO treatment reduced reinstatement of cocaine-seeking (e.g., Anker et al, 2009; Feltenstein et al, 2009; for a review, see Carroll and Anker, 2010; Anker and Carroll, 2011), prevented the escalation of cocaine self-administration (Larson et al 2007), decreased cocaine-induced stereotyped behaviors (Souza et al, 2014) and reduced impulsivity for cocaine self-administration (Smethells et al, under review).…”

Section: Introductionmentioning

confidence: 99%

Sex differences in reinstatement of cocaine-seeking with combination treatments of progesterone and atomoxetine

Swalve

Smethells

Zlebnik

et al. 2016

Pharmacology Biochemistry and Behavior

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Two repurposed medications have been proposed to treat cocaine abuse. Progesterone, a gonadal hormone, and atomoxetine, a medication commonly used to treat attention deficit/hyperactivity disorder, have both been separately shown to reduce cocaine self-administration and reinstatement (i.e. relapse). The goal of the present study was to examine sex differences in the individual effects of PRO and ATO as well as the combination PRO+ATO treatment on cocaine (COC), caffeine (CAF), and/or cue-primed reinstatement of cocaine-seeking. Adult male and female Wistar rats lever-pressed under a FR 1 schedule for cocaine infusions (0.4 mg/kg/inf). After 14 sessions of stable responding in daily 2-h sessions, rats underwent a 21-day extinction period when no drug or drug-related stimuli were present. Rats were then separated into four groups that received PRO (0.5 mg/kg) alone (PRO+SAL), ATO (1.5 mg/kg) alone (VEH+ATO), control (VEH+SAL) or combination (PRO+ATO) treatments prior to the reinstatement condition. Reinstatement of cocaine-seeking to cues and/or drug injections of cocaine or caffeine was tested after extinction. During maintenance, females self-administered more cocaine than males, but no sex differences were seen during extinction. Females showed greater cocaine-seeking than males after a CAF priming injection. Individual treatment with ATO did not decrease reinstatement under any priming condition; however, the combination treatment decreased cocaine-seeking under the COC+CUES priming condition in males, and both PRO alone and the combination treatment decreased cocaine-seeking in the CAF+CUES condition in females. Overall, PRO alone was only effective in reducing reinstatement in females, while the combination treatment was consistently effective in reducing reinstatement in both sexes.

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“…Circulating estradiol and progesterone levels are low in ovariectomized females, and the uterine weight will decrease to <15% of normal (Fig. 1B) [20, 41, 42]. DESeq2, Limma, and Cuffdiff were used to identify transcripts expressed at substantially different levels in ovariectomized/placebo vs cycling female mice.…”

Section: Resultsmentioning

confidence: 99%

Sex-Specific Gene Expression in the Mouse Nucleus Accumbens Before and After Cocaine Exposure

LaRese

Rheaume

Abraham

et al. 2019

Journal of the Endocrine Society

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The nucleus accumbens plays a major role in the response of mammals to cocaine. In animal models and human studies, the addictive effects of cocaine and relapse probability have been shown to be greater in females. Sex-specific differential expression of key transcripts at baseline and after prolonged withdrawal could underlie these differences. To distinguish between these possibilities, gene expression was analyzed in four groups of mice (cycling females, ovariectomized females treated with estradiol or placebo, and males) 28 days after they had received seven daily injections of saline or cocaine. As expected, sensitization to the locomotor effects of cocaine was most pronounced in the ovariectomized mice receiving estradiol, was greater in cycling females than in males, and failed to occur in ovariectomized/placebo mice. After the 28-day withdrawal period, RNA prepared from the nucleus accumbens of the individual cocaine- or saline-injected mice was subjected to RNA sequencing analysis. Baseline expression of 3% of the nucleus accumbens transcripts differed in the cycling female mice compared with the male mice. Expression of a similar number of transcripts was altered by ovariectomy or was responsive to estradiol treatment. Nucleus accumbens transcripts differentially expressed in cycling female mice withdrawn from cocaine exhibited substantial overlap with those differentially expressed in cocaine-withdrawn male mice. A small set of transcripts were similarly affected by cocaine in the placebo- or estradiol-treated ovariectomized mice. Sex and hormonal status have profound effects on RNA expression in the nucleus accumbens of naive mice. Prolonged withdrawal from cocaine alters the expression of a much smaller number of common and sex hormone-specific transcripts.

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Behavioral effects of endogenous or exogenous estradiol and progesterone on cocaine sensitization in female rats

Cited by 26 publications

References 38 publications

Increasing Progesterone Levels Are Associated With Smoking Abstinence Among Free-Cycling Women Smokers Who Receive Brief Pharmacotherapy

Increasing Progesterone Levels Are Associated With Smoking Abstinence Among Free-Cycling Women Smokers Who Receive Brief Pharmacotherapy

Sex differences in reinstatement of cocaine-seeking with combination treatments of progesterone and atomoxetine

Sex-Specific Gene Expression in the Mouse Nucleus Accumbens Before and After Cocaine Exposure

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