Estradiol lowers intracranial self-stimulation thresholds and enhances cocaine facilitation of intracranial self-stimulation in rats

Galankin, T.; Shekunova, E.V.; Zvartau, Edwin

doi:10.1016/j.yhbeh.2010.08.006

Cited by 20 publications

(14 citation statements)

References 65 publications

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“…Males and females do not differ with regard to baseline sensitivity to the reinforcing effects of electrical stimulation of the MFB, and sensitivity in females is also stable across stages of the estrous cycle (Stratmann and Craft, 1997;Russell et al, 2013). However, exogenously administered estradiol facilitates ICSS in ovariectomized female rats (Galankin et al, 2010) and exogenous testosterone facilitates ICSS in castrated male rats (Olds, 1958a). These findings suggest that baseline sex differences in ICSS do not exist, but artificial manipulation of sex hormones is sufficient to alter ICSS.…”

Section: A Statesmentioning

confidence: 80%

“…Regarding the role of sex in the effects of drugs of abuse on ICSS, the monoamine releaser amphetamine and the uptake inhibitor cocaine facilitated ICSS to a similar degree in male and female rats responding under a discrete-trial current-intensity threshold procedure (Stratmann and Craft, 1997), but administration of exogenous estradiol enhanced cocaine-induced ICSS facilitation in ovariectomized female rats (Galankin et al, 2010). Sex also does not appear to play a major role in cocaine self-administration in rats (Caine et al, 2004), although estradiol administration to ovariectomized rats increased cocaine self-administration under a progressive ratio procedure (Ramoa et al, 2013).…”

Section: A Statesmentioning

confidence: 99%

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Intracranial Self-Stimulation to Evaluate Abuse Potential of Drugs

2014

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Section: A Statesmentioning

confidence: 80%

Section: A Statesmentioning

confidence: 99%

Intracranial Self-Stimulation to Evaluate Abuse Potential of Drugs

2014

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“…Progesterone attenuates cocaine reward in humans and rats [6,20] and estrogen also plays an important role in cocaine reward. In ovariectomized rats, estradiol itself can induce CPP [21], increase the sensitivity of the brain to reward as measured by intracranial self-stimulation [22], and enhance cocaine CPP [23,24]. The ability of estradiol to enhance cocaine reward may be due to the expression of estrogen receptor alpha (ERα) in the nucleus accumbens, since administration of antisense oligonucleotides targeting ERα into the nucleus accumbens can reduce estradiol-induced CPP [25].…”

Section: Discussionmentioning

confidence: 99%

Sex differences in cocaine conditioned place preference in C57BL/6J mice

Hilderbrand

Lasek

2014

NeuroReport

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Men and women respond differently to the subjective effects of cocaine and cocaine-associated cues, which has implications for the development and maintenance of cocaine addiction. Preclinical studies performed in rats, modeling various aspects of cocaine addiction, have largely validated these results, indicating that female rats may be more sensitive to the rewarding properties of cocaine. The molecular mechanisms leading to sex differences in cocaine reward have largely not been determined, although sex hormones are thought to play a role. The mouse is commonly used as a model organism to study the molecular and genetic factors that influence a variety of psychiatric disorders. In particular, the inbred C57BL/6 mouse strain is often used for behavioral studies related to substance abuse. To begin to understand the hormonal, molecular and genetic mechanisms that might affect cocaine reward, we directly compared male and female C57BL/6J mice in cocaine conditioned place preference (CPP), a test that examines the rewarding and cue-associated properties of drugs of abuse. We conditioned mice at three doses of cocaine and examined preference and extinction of preference. We found that the acquisition of cocaine CPP did not differ between male and female mice. However, extinction of cocaine CPP was delayed in male mice compared to females at the lowest dose of cocaine. We conclude that sex differences in cocaine CPP can be observed in C57BL/6J mice at very low doses of cocaine.

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“…Female rats exhibit enhanced responding to psychostimulants in multiple paradigms in a manner both dependent and independent of ovarian sex hormones (Hu et al 2004;Jackson et al 2006). In ovariectomized rats, E 2 enhances the sensitization of cocaine-induced locomotor behavior and CPP (Segarra et al 2010), self-administration of cocaine on both fixed and progressive ratio schedules of reinforcement (Lynch and Taylor 2005;Zhao and Becker 2010), and preference for cocaine over food reinforcement in a discrete trials procedure (Kerstetter and Kippin 2011), and lowers thresholds for electrical brain stimulation of the ventral tegmental area (Galankin et al 2010). Thus, E 2 -enhanced expression of CPP could be interpreted as further evidence in females of "enhanced abuse liability to cocaine," yet this interpretation is at odds with the finding that E 2 also enhanced extinction of drug seeking.…”

Section: Discussionmentioning

confidence: 99%

17β-Estradiol is necessary for extinction of cocaine seeking in female rats

et al. 2013

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Human and preclinical models of addiction demonstrate that gonadal hormones modulate acquisition of drug seeking. Little is known, however, about the effects of these hormones on extinction of drug-seeking behavior. Here, we investigated how 17b-estradiol (E 2 ) affects expression and extinction of cocaine seeking in female rats. Using a conditioned place preference (CPP) paradigm, ovariectomized rats were maintained throughout conditioning with 2 d of E 2 treatment followed by 2 d of vehicle treatment, or were injected with E 2 daily. Hormone injections were paired or explicitly unpaired with place conditioning sessions. Expression of a cocaine CPP was of equal magnitude regardless of conditioning protocol, suggesting that E 2 levels during conditioning did not affect subsequent CPP expression. During extinction, daily E 2 administration initially enhanced expression of the cocaine CPP, but resulted in significantly faster extinction compared to controls. Whereas E 2 -treated rats were extinguished within 8 d, vehicle-treated rats maintained CPP expression for more than a month, indicative of perseveration. To determine whether E 2 could rescue extinction in these rats, half were given daily E 2 treatment and half were given vehicle. E 2 -treated rats showed rapid extinction, whereas vehicle-treated rats continued to perseverate. These data demonstrate for the first time that E 2 is necessary for extinction of cocaine seeking in female rats, and that it promotes rapid extinction when administered daily. Clinically, these findings suggest that monitoring and maintaining optimal E 2 levels during exposure therapy would facilitate therapeutic interventions for female cocaine addicts.Gonadal hormones render women more susceptible than men to developing compulsive patterns of psychostimulant use. Natural fluctuations in levels of the primary ovarian hormones, estrogens and progesterone, account for this increased abuse liability. Higher levels of estrogens, and lower levels of progesterone, are associated with greater sensitivity to the euphorigenic properties of cocaine in women (Evans 2007). This increased sensitivity may contribute to why women, compared with men, start using cocaine regularly at a younger age (Chen and Kandel 2002), transition from use to abuse more quickly (McCance-Katz et al. 1999), experience greater craving in response to drug-associated cues (Robbins et al. 1999) and stress (Potenza et al. 2012;Waldrop et al. 2012), and exhibit more severe drug-seeking behavior upon relapse (Gallop et al. 2007). In contrast, more women than men remain abstinent after treatment (Weiss et al. 1997). Thus, women are both more susceptible to cocaine abuse and, paradoxically, more responsive to treatment.A substantial literature supports that estrogens mediate the enhancement of drug seeking observed in females (Febo et al. 2002;Larson et al. 2007;Segarra et al. 2010; Kerstetter and Kippin 2011), but little is known regarding the role of estrogens during treatment. Preclinically, treatment is modeled through ext...

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Estradiol lowers intracranial self-stimulation thresholds and enhances cocaine facilitation of intracranial self-stimulation in rats

Cited by 20 publications

References 65 publications

Intracranial Self-Stimulation to Evaluate Abuse Potential of Drugs

Intracranial Self-Stimulation to Evaluate Abuse Potential of Drugs

Sex differences in cocaine conditioned place preference in C57BL/6J mice

17β-Estradiol is necessary for extinction of cocaine seeking in female rats

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