Estrogen and Progesterone Modulation of Cocaine-Seeking Behavior in Female Rats

Anker, Justin J.; Larson, Erin B.; Gliddon, Luke A.; Carroll, Marilyn E.

doi:10.1037/e678312007-001

Cited by 2 publications

(2 citation statements)

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“…In that study, progesterone treatment attenuated the positive subjective effects from cocaine only in female cocaine users. These human studies are in agreement with preclinical studies, which showed that progesterone treatment may block the rewarding effects of cocaine (Anker, Larson, & Carroll, 2006; Feltenstein & See, 2007; Jackson, Robinson, & Becker, 2006; Mello, Knudson, & Mendelson, 2007; Romieu, Martin-Fardon, Bowen, & Maurice, 2003). Progesterone and its active metabolites, allopregnanolone and pregnanolone, have wide-ranging effects on neurotransmitter receptors, including positive modulatory effects on GABA A and negative modulatory effects on N -methyl- d -aspartate receptors (Cyr et al, 2001; Smith, 1991).…”

supporting

confidence: 89%

Progesterone effects on cocaine use in male cocaine users maintained on methadone: A randomized, double-blind, pilot study.

Sofuoglu

Poling

González

et al. 2007

Experimental and Clinical Psychopharmacology

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Previously, the authors reported that progesterone treatment attenuated reports of cocaine-induced high in male and female cocaine users. In this pilot clinical trial, the authors tested the safety and efficacy of oral progesterone as a treatment for cocaine dependence in methadone-stabilized male cocaine users. This was a 10-week, randomized, double-blind, placebo-controlled trial. Forty-five male methadone-stabilized cocaine users were randomized to receive placebo (n=15) or progesterone (n=30) for 9 weeks. The progesterone dose was gradually increased from 100 mg to 300 mg twice daily by Week 4 and maintained through Week 10. Treatment retention for the clinical trial was 80%, without significant group differences (log rank=2.4, p=.12). Hierarchical linear modeling estimates of obtaining a cocaine positive urine result across 10 weeks showed a very slight reduction in cocaine use for the progesterone group (Z=-2.89, p<.004). The placebo group showed a slight increase in cocaine use from Week 1 to Week 10 (Z=2.72, p<.007). These slopes significantly differed from each other (Z=-3.83, p<.0001). Overall, the placebo group showed significantly lower probability of having a cocaine positive urine result at treatment's end (Weeks 9 and 10) compared with the progesterone group (0.60 vs. 0.73; U=4837, p<.04). These preliminary findings do not support the efficacy of progesterone in male cocaine users. The efficacy of progesterone in female cocaine users remains to be determined in future studies.

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supporting

confidence: 89%

Progesterone effects on cocaine use in male cocaine users maintained on methadone: A randomized, double-blind, pilot study.

Sofuoglu

Poling

González

et al. 2007

Experimental and Clinical Psychopharmacology

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“…Recent preclinical studies have shown that P decreases the rewarding effects of cocaine and influences cocaine self-administration. In ovariectomized rats that were primed with E, P reduced the acquisition of cocaine self-administration (Jackson, Robinson, & Becker, 2006), whereas in intact rats, P reduced cocaine-induced reinstatement (Anker, Larson, & Carroll, 2006). Similarly, in female rhesus monkeys, P treatment dose dependently reduced cocaine self-administration behavior (Mello, Mendelson, Knudson, & Kelly, 2005).…”

Section: Discussionmentioning

confidence: 99%

Sex steroid hormones, stress response, and drug craving in cocaine-dependent women: Implications for relapse susceptibility.

Sinha¹,

Fox²,

Hong³

et al. 2007

Experimental and Clinical Psychopharmacology

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Cocaine dependence is associated with an enhanced sensitivity to stress and drug craving. Increases in stress-induced craving and hypothalamic-pituitary-adrenal reactivity are also predictive of cocaine relapse outcomes. More important, sex differences in these responses have also been reported. To further understand the basis of the sex differences, the authors examined the influence of sex steroid hormones on subjective and physiological stress responses and drug craving in cocaine-dependent women. Women who had low progesterone levels (n=5) were compared with those with high progesterone levels (n=5) and with those with moderate levels of estradiol and progesterone (n=9) in their responses during exposure to stress, cocaine cues, and neutral imagery conditions. The high progesterone group showed significantly lower stress-induced and drug cue-induced cocaine craving ( p<.05) and reduced drug cue-induced anxiety levels ( p<.08) and lower drug cue-induced systolic and diastolic blood pressure levels compared with the low progesterone group. These data suggest that there are significant effects of sex steroid hormones on stress and drug cue-induced cocaine craving, anxiety, and cardiovascular responses. In particular, high progesterone during the midluteal phase of the cycle was associated with decreased stress-induced and drug cue-induced craving and decreased cue-induced anxiety and blood pressure responses. These findings are consistent with previous preclinical and clinical studies of progesterone's effects on the behavioral responses to cocaine and warrant further research to examine the effects of progesterone on stress-induced cocaine craving, stress arousal, and cocaine relapse susceptibility in women.

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Estrogen and Progesterone Modulation of Cocaine-Seeking Behavior in Female Rats

Cited by 2 publications

References 0 publications

Progesterone effects on cocaine use in male cocaine users maintained on methadone: A randomized, double-blind, pilot study.

Progesterone effects on cocaine use in male cocaine users maintained on methadone: A randomized, double-blind, pilot study.

Sex steroid hormones, stress response, and drug craving in cocaine-dependent women: Implications for relapse susceptibility.

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