PKA-mediated responses in females' estrous cycle affect cocaine-induced responses in dopamine-mediated intracellular cascades

Weiner, Jan; Sun, Wei; Zhou, Luyi; Kreiter, C.M.; Jenab, Shirzad; Quiñones-Jenab, Vanya

doi:10.1016/j.neuroscience.2009.03.071

Cited by 11 publications

(6 citation statements)

References 67 publications

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“…However, some cocaine-induced phospho-protein levels have been shown to vary based on estrous cycle stage. For example, previous research shows that NAc pCREB increased 15 minutes after cocaine exposure in estrus females, but no basal differences in NAc or CPu pCREB or ΔFosB were seen based on cycle stage (Weiner et al 2009). Therefore, our results are likely not due to estrous cycle effects, but more likely due to sex differences in neural organization utilizing sex specific intracellular responses.…”

Section: Discussionmentioning

confidence: 92%

Sexually dimorphic intracellular responses after cocaine-induced conditioned place preference expression

et al. 2013

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Sex differences in cocaine’s mechanisms of action and behavioral effects have been widely reported. However, little is known about how sex influences intracellular signaling cascades involved with drug-environment associations. We investigated whether ERK/CREB intracellular responses in the mesocorticolimbic circuitry underlying cocaine environmental associations are sexually dimorphic. We used a standard 4 day conditioned place preference (CPP) paradigm using 20mg/kg cocaine—a dose that induced CPP in male and female Fischer rats. In the nucleus accumbens (NAc) following CPP expression, cocaine treated animals showed increased phosphorylated ERK (pERK), phosphorylated CREB (pCREB) and ΔFosB protein levels. In the hippocampus (HIP) and caudate putamen (CPu), pERK and FosB/ΔFosB levels were also increased, respectively. Cocaine females had a larger change in HIP pERK and CPu ΔFosB levels than cocaine males; partly due to lower protein levels in saline female rats when compared to saline males. Prefrontal cortex (PfC) pCREB levels increased in cocaine males, but not females, whereas PfC pERK levels were increased in cocaine females, but not males. CPP scores were positively correlated to NAc pERK, HIP pERK and CPu FosB protein levels, suggesting that similar to males, the ERK/CREB intracellular pathway in mesocorticolimbic regions undergoes cocaine induced neuroplasticity in female rats. However, there seem to be intrinsic (basal) sexual dimorphisms in this pathway that may contribute to responses expressed after cocaine-CPP. Taken together, our results suggest that cellular responses associated with the expression of learned drug-environment associations may play an important role in sex differences in cocaine addiction and relapse.

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Section: Discussionmentioning

confidence: 92%

Sexually dimorphic intracellular responses after cocaine-induced conditioned place preference expression

et al. 2013

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“…Studies have also shown E2 regulation of cAMP and PKA pathways. For example, the estrous cycle seems to affect the activity of a variety of intracellular signaling cascades in the NAc of female rats regardless of cocaine-treatment (Weiner et al, 2009). Ovariectomized females have been used in attempts to identify a role of E2 on these intracellular signaling cascades.…”

Section: Sex Differences In Signaling Mechanisms Of Cocaine Addictionmentioning

confidence: 99%

Sex Differences and the Role of Estradiol in Mesolimbic Reward Circuits and Vulnerability to Cocaine and Opiate Addiction

Kokane

Perrotti

2020

Front. Behav. Neurosci.

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Although both men and women become addicted to drugs of abuse, women transition to addiction faster, experience greater difficulties remaining abstinent, and relapse more often than men. In both humans and rodents, hormonal cycles are associated with females' faster progression to addiction. Higher concentrations and fluctuating levels of ovarian hormones in females modulate the mesolimbic reward system and influence reward-directed behavior. For example, in female rodents, estradiol (E2) influences dopamine activity within the mesolimbic reward system such that drugdirected behaviors that are normally rewarding and reinforcing become enhanced when circulating levels of E2 are high. Therefore, neuroendocrine interactions, in part, explain sex differences in behaviors motivated by drug reward. Here, we review sex differences in the physiology and function of the mesolimbic reward system in order to explore the notion that sex differences in response to drugs of abuse, specifically cocaine and opiates, are the result of molecular neuroadaptations that differentially develop depending upon the hormonal state of the animal. We also reconsider the notion that ovarian hormones, specifically estrogen/estradiol, sensitize target neurons thereby increasing responsivity when under the influence of either cocaine or opiates or in response to exposure to drug-associated cues. These adaptations may ultimately serve to guide the motivational behaviors that underlie the factors that cause women to be more vulnerable to cocaine and opiate addiction than men.

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“…Immediate early gene expression was similar in all the female groups irrespective of hormone treatment, suggesting equivalent activation of MSN by cocaine. The activity of various intracellular signaling cascades in the striatum fluctuates over the estrous cycle [359]. Thus, drug exposure may translate into different patterns of DYN and immediate early gene expression depending upon the hormonal milieu.…”

Section: Introductionmentioning

confidence: 99%

Sex differences in the neural mechanisms mediating addiction: a new synthesis and hypothesis

2012

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In this review we propose that there are sex differences in how men and women enter onto the path that can lead to addiction. Males are more likely than females to engage in risky behaviors that include experimenting with drugs of abuse, and in susceptible individuals, they are drawn into the spiral that can eventually lead to addiction. Women and girls are more likely to begin taking drugs as self-medication to reduce stress or alleviate depression. For this reason women enter into the downward spiral further along the path to addiction, and so transition to addiction more rapidly. We propose that this sex difference is due, at least in part, to sex differences in the organization of the neural systems responsible for motivation and addiction. Additionally, we suggest that sex differences in these systems and their functioning are accentuated with addiction. In the current review we discuss historical, cultural, social and biological bases for sex differences in addiction with an emphasis on sex differences in the neurotransmitter systems that are implicated.

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PKA-mediated responses in females' estrous cycle affect cocaine-induced responses in dopamine-mediated intracellular cascades

Cited by 11 publications

References 67 publications

Sexually dimorphic intracellular responses after cocaine-induced conditioned place preference expression

Sexually dimorphic intracellular responses after cocaine-induced conditioned place preference expression

Sex Differences and the Role of Estradiol in Mesolimbic Reward Circuits and Vulnerability to Cocaine and Opiate Addiction

Sex differences in the neural mechanisms mediating addiction: a new synthesis and hypothesis

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