Progesterone attenuates cocaine-induced conditioned place preference in female rats

Russo, Scott J.; Sun, Wei; Minerly, Ana Christina E.; Weierstall, Karen; Nazarian, Arbi; Festa, Eugene D.; Niyomchai, Tipyamol; Akhavan, Alaleh; Luine, Victoria N.; Jenab, Shirzad; Quiñones-Jenab, Vanya

doi:10.1016/j.brainres.2007.10.057

Cited by 40 publications

(32 citation statements)

References 43 publications

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“…While one study found a significant attenuation of positive subjective effects and cardiovascular responses in men (Sofuoglu et al 2004), another found little to no effect on cocaine's subjective effects (Evans and Foltin 2006) and cocaine use (Sofuoglu et al 2007) and only dose-dependent decreases in cardiovascular responses to cocaine (Evans and Foltin 2006) in males. These equivocal findings are in accordance with rodent studies demonstrating P treatment as both effective (Romieu et al 2003) and ineffective (Russo et al 2010) in decreasing cocaine conditioned place preference in males. Overall, few investigations have examined the role of P to reduce cocaine-motivated behavior in males, and the results of this experiment suggest that treatment with P under the present conditions reduces cocaine seeking in male rats.…”

Section: Discussionsupporting

confidence: 87%

Effects of combined exercise and progesterone treatments on cocaine seeking in male and female rats

2014

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BACKGROUND Individually, both treatment with progesterone and concurrent access to an exercise wheel reduce cocaine self-administration under long-access conditions and suppress cocaine-primed reinstatement in female rats. In the present study, wheel running and progesterone (alone and combined) were assessed for their effects on reinstatement of cocaine-seeking primed by yohimbine, cocaine, and cocaine-paired cues. METHODS Male and female rats were implanted with an intravenous catheter and allowed to self-administer cocaine (0.4 mg/kg/inf, iv) during 6-h sessions for 10 days. Subsequently, the groups of male and female rats were each divided into 2 groups that were given concurrent access to either a locked or unlocked running wheel under extinction conditions for 14 days. Next, all 4 groups were tested in a within-subjects design for reinstatement of cocaine-seeking precipitated by separate administration of cocaine-paired stimuli, yohimbine, or cocaine; or the combination of yohimbine + cocaine-paired stimuli or cocaine + cocaine-paired stimuli. These priming conditions were tested in the presence of concurrent wheel access (W), pretreatment with progesterone (P), or both (W+P). RESULTS In agreement with previous results, females responded more for cocaine than males during maintenance. Additionally, concurrent wheel running attenuated extinction responding and cocaine-primed reinstatement in females but not males. Across all priming conditions, W+P reduced reinstatement compared to control conditions, and for cocaine-primed reinstatement in male rats, the combined W+P treatment was more effective than W or P alone. CONCLUSION Under certain conditions, combined behavioral (exercise) and pharmacological (progesterone) interventions were more successful at reducing cocaine-seeking behavior than either intervention alone.

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Section: Discussionsupporting

confidence: 87%

Effects of combined exercise and progesterone treatments on cocaine seeking in male and female rats

2014

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“…Early abstinence from cocaine is associated with robust GABAergic and corticotropin-releasing factor (CRF) adaptations within selective regions of the prefrontal cortex that are concomitant with cognitive and inhibitory control dysregulation (George et al, 2012; Peters et al, 2008). Allopregnanolone increases GABAergic currents and thereby modulates GABA-activated inhibition of neural firing in dopaminergic regions of the prefrontal cortex (Becker, 1999; Becker and Hu, 2008; Russo et al, 2008). Such increases in GABA-activated neural inhibition may represent a possible mechanism to explain current findings of overall improved Stroop performance in cocaine dependent individuals treated with progesterone.…”

Section: Discussionmentioning

confidence: 99%

Effects of progesterone stimulated allopregnanolone on craving and stress response in cocaine dependent men and women

Milivojevic

Fox

Sofuoglu³

et al. 2016

Psychoneuroendocrinology

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Objectives Fluctuations in progesterone levels during the menstrual cycle have been shown to affect physiological and subjective effects of cocaine. Furthermore, our laboratory has demonstrated that following drug-cue exposure, cocaine dependent women with high levels of circulating progesterone display lower diastolic and systolic blood pressure responses and report lower levels of anxiety and drug craving compared to cocaine dependent women with low levels of progesterone. In the current study we examined the role of the progesterone derived neuroactive steroid allopregnanolone (ALLO) on stress arousal, inhibitory control and drug craving in cocaine dependent subjects. Methods Plasma levels of ALLO were measured using GC/MS in 46 treatment-seeking cocaine dependent men and women on day 5 of a 7-day treatment regimen of micronized progesterone (15M / 8F) (400mg/day) or placebo (14M / 9F) administered in a double blind, randomized manner. As a control, levels of the testosterone derived neurosteroid androstanediol (ADIOL) were also measured. All subjects participated in laboratory sessions on days 5–7 of progesterone/placebo administration in which they were exposed to a series of 5-min personalized guided imagery of either a stressful situation, cocaine use or of a neutral setting and dependent variables including subjective craving, mood, Stroop task as a measure of inhibitory control performance and plasma cortisol were assessed. Participants were grouped by high or low ALLO level and levels of dependent variables compared between ALLO groups. Results Progesterone relative to placebo significantly increased ALLO levels with no sex differences. There were no effects of micronized progesterone on the testosterone derived ADIOL. Individuals in the high versus the low ALLO group showed decreased levels of cortisol at baseline, and a higher cortisol response to stress; higher positive mood scores at baseline and improved Stroop performance in the drug-cue and stress conditions, and reduced cocaine craving across all imagery conditions. Conclusions As expected, cocaine dependent individuals administered progesterone showed significantly higher ALLO plasma levels. High levels of ALLO appeared to normalize basal and stress response levels of cortisol, decrease cocaine craving and also contribute to improvements in positive emotion and Stroop performance in response to stress and drug-cue exposures. These findings suggest that the neuroactive steroid ALLO plays a significant role in mediating the positive effects of progesterone on stress arousal, cognitive performance and drug craving in cocaine dependence.

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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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Progesterone attenuates cocaine-induced conditioned place preference in female rats

Cited by 40 publications

References 43 publications

Effects of combined exercise and progesterone treatments on cocaine seeking in male and female rats

Effects of combined exercise and progesterone treatments on cocaine seeking in male and female rats

Effects of progesterone stimulated allopregnanolone on craving and stress response in cocaine dependent men and women

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

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