Gonadal hormones differentially modulate cocaine-induced conditioned place preference in male and female rats

Russo, Scott J.; Festa, Eugene D.; Fabian, Sosimo J.; Gazi, Farhad M.; Kraish, M; Jenab, Shirzad; Quiñones-Jenab, Vanya

doi:10.1016/s0306-4522(03)00317-8

Cited by 162 publications

(113 citation statements)

References 43 publications

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“…Given that motivated behaviors, such as sexual behavior and drug-taking behavior, are mediated by overlapping neural systems (Everitt et al, 1974(Everitt et al, , 1975Kelley and Berridge, 2002), including DA systems (Mermelstein and Becker, 1995;Pfaus et al, 1990;Phillips et al, 1991;Vezina, 1993), perhaps it is not surprising that progesterone has inhibitory effects on cocaine self-administration behavior. Furthermore, several recent publications have postulated that progesterone attenuates cocaine-induced behavioral activation (Sell et al, 2000;Russo et al, 2003;Festa and Quinones-Jenab, 2004); however, this is the first study to demonstrate that progesterone inhibits cocaine-taking behavior in rats.…”

Section: Relevance To Existing Literaturementioning

confidence: 66%

“…Thus, inhibited cocaine self-administration is not likely due to an aversive subjective state. In female rats, chronic estradiol and progesterone treatment was found to enhance conditioned place preference for cocaine in female rats, relative to controls (Russo et al, 2003), this suggests that estradiol and progesterone do not create an aversive subjective effect in rats. The hormone treatment paradigm used in the study reported here is quite different from that used by Russo et al (2003), so future studies will need to investigate whether acute treatment with estradiol and progesterone affects conditioned place preference for cocaine.…”

Section: Relevance To Existing Literaturementioning

confidence: 79%

“…If acute estradiol plus progesterone treatment, as used in the study reported here, diminishes the reinforcing effects of cocaine in rats, then this could contribute to the findings reported. On the other hand, given the findings of Russo et al (2003), effects of hormone treatment on the subjective hedonic value of cocaine do not necessarily underlie the influence of hormones on acquisition of self-administration of cocaine.…”

Section: Possible Mechanisms Of Progesterone Actionmentioning

confidence: 95%

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Sex Differences and Hormonal Influences on Acquisition of Cocaine Self-Administration in Rats

Jackson

Robinson

Becker

2005

Neuropsychopharmacol

285

272

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Men and women differ in their response to cocaine, and a woman's response varies with the menstrual cycle. For example, women have greater subjective responses to cocaine in the follicular phase of the menstrual cycle when estradiol is predominant, than they do during the luteal phase when both estradiol and progesterone are elevated. Similarly, female rats show significantly more cocaine-induced locomotor behavior and cocaine self-administration during behavioral estrus, shortly after estradiol peaks, than during other stages of the cycle, and estradiol administration to ovariectomized (OVX) females enhances the acquisition of cocaine self-administration. The purpose of this study was to expand upon these findings by studying the effects of progesterone administration to females, and estradiol administration to males, on acquisition of cocaine self-administration. We report here that there are both sex differences in and effects of circulating ovarian hormones on acquisition of cocaine self-administration. We demonstrate that although estradiol administration enhances acquisition of cocaine self-administration in OVX female rats, concurrent administration of progesterone with estradiol inhibits this effect of estradiol. In a separate experiment, we demonstrate that estradiol administration does not enhance acquisition of cocaine self-administration in castrated male rats. We conclude that (1) there is a sex difference in the effects of estradiol on cocaine selfadministration: it facilitates acquisition in female, but not male rats; and that (2) in females concurrent progesterone treatment counteracts the facilitory effect of estradiol on cocaine self-administration.

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Section: Relevance To Existing Literaturementioning

confidence: 66%

Section: Relevance To Existing Literaturementioning

confidence: 79%

Section: Possible Mechanisms Of Progesterone Actionmentioning

confidence: 95%

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Sex Differences and Hormonal Influences on Acquisition of Cocaine Self-Administration in Rats

Jackson

Robinson

Becker

2005

Neuropsychopharmacol

285

272

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“…Early postpartum is characterized by very low concentrations of estrogen and high concentrations of progesterone and prolactin; concentrations gradually shift back to the normal cycling state during late postpartum (Grota and Eik-Nes 1967;Smith and Neill 1977;Taya and Greenwald 1982). Although low estrogen concentrations are associated with reduced cocaine self-administration (Roberts et al 1989;Hecht et al 1999) and high progesterone concentrations with attenuated cocaine CPP (Russo et al 2003a(Russo et al , 2008, cocaine CPP remains nearly identical in early and late postpartum, suggesting that cocaine CPP may be relatively insensitive to subtle hormonal changes occurring across the postpartum period. Collectively, however, we believe that the unique endogenous combinations and concentrations of gonadal and lactogenic hormones present across postpartum may establish a prolonged period that subtly alters and increases the incentive value of cocaine.…”

Section: Discussionmentioning

confidence: 99%

“…While cocaine CPP is influenced by sex (Russo et al 2003b;Carroll et al 2004;Jackson et al 2006), estrus cycle stage (Roberts et al 1989;Hecht et al 1999), and exogenous administration of ovarian hormones (Russo et al 2003a(Russo et al , 2008, little research exists on cocaine CPP across the postpartum period, a complex phase characterized by subtle fluctuations in endogenous ovarian hormones and neuroactive peptides and influenced uniquely by biologically relevant stimuli (i.e., pups). The present study constitutes the first systematic examination of cocaine's incentive value across this unique period in the natural lifecycle of the female rat.…”

Section: Introductionmentioning

confidence: 99%

Incentive salience of cocaine across the postpartum period of the female rat

et al. 2008

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Rationale-Objectives-Our prior conditioned place preference (CPP) work demonstrates that late (day16) postpartum female rats consistently prefer cocaine-over pup-associated chambers, whereas far fewer early postpartum (day8) females prefer the cocaine-associated chamber. The present study examines early and late postpartum females' preference for a cocaine-associated chamber when contrasted with a chamber associated with saline (rather than pups).Materials and methods-Postpartum females were tested for conditioned preference for chambers associated with cocaine (10 mg/kg subcutaneous (SC) or 0.5, 5, 10, or 20 mg/kg intraperitoneal (IP) injections) versus saline; preferences of virgin female and male rats for select cocaine stimuli (10mg/kg SC or IP) were also tested. Locomotion was recorded during CPP conditioning and testing.Results-Early and late postpartum females expressed strikingly similar preference for the cocaineassociated chamber across all administration routes and doses. IP cocaine produced an orderly, inverted U-shaped dose-preference curve, with preference peaking at the 5 mg/kg dose (83% of females). While many postpartum females preferred 10mg/kg cocaine administered either SC or IP, both virgin females and males expressed strong aversion to SC cocaine and, while virgin females strongly preferred IP cocaine, males remained relatively indifferent. Across 10mg/kg IP cocaineconditioning sessions, locomotor sensitization occurred exclusively in cocaine-but not salinepreferring postpartum females. Locomotor rate was lower in preferred versus nonpreferred chambers at CPP test.Conclusions-Early and late postpartum females may be equally and uniquely susceptible to sampling and/or abuse of modestly salient doses of cocaine (10mg/kg SC; 5mg/kg IP) compared to virgin females and/or males.

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Quantitative analysis of pre‐ and postsynaptic sex differences in the nucleus accumbens

Forlano¹,

Woolley²

2010

J of Comparative Neurology

109

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The nucleus accumbens (NAc) plays a central role in motivation and reward. While there is ample evidence for sex differences in addiction-related behaviors, little is known about the neuroanatomical substrates that underlie these sexual dimorphisms. We investigated sex differences in synaptic connectivity of the NAc by evaluating pre- and postsynaptic measures in gonadally intact male and proestrous female rats. We used DiI labeling and confocal microscopy to measure dendritic spine density, spine head size, dendritic length and branching of medium spiny neurons (MSNs) in the NAc, and quantitative immunofluorescence to measure glutamatergic innervation using pre- (vesicular glutamate transporter 1 and 2) and postsynaptic (post synaptic density 95) markers, as well as dopaminergic innervation of the NAc. We also utilized electron microscopy to complement the above measures. Clear but subtle sex differences were identified, namely in distal dendritic spine density and the proportion of large spines on MSNs, both of which are greater in females. Sex differences in spine density and spine head size are evident in both the core and shell subregions, but are stronger in the core. This study is the first demonstration of neuroanatomical sex differences in the NAc and provides evidence that structural differences in synaptic connectivity and glutamatergic input may contribute to behavioral sex differences in reward and addiction.

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Gonadal hormones differentially modulate cocaine-induced conditioned place preference in male and female rats

Cited by 162 publications

References 43 publications

Sex Differences and Hormonal Influences on Acquisition of Cocaine Self-Administration in Rats

Sex Differences and Hormonal Influences on Acquisition of Cocaine Self-Administration in Rats

Incentive salience of cocaine across the postpartum period of the female rat

Quantitative analysis of pre‐ and postsynaptic sex differences in the nucleus accumbens

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