Concurrent Exposure to Methamphetamine and Sexual Behavior Enhances Subsequent Drug Reward and Causes Compulsive Sexual Behavior in Male Rats

Frohmader, Karla S.; Lehman, Michael N.; Laviolette, Steven R.; Coolen, Lique M.

doi:10.1523/jneurosci.4013-11.2011

Cited by 27 publications

(24 citation statements)

References 84 publications

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“…However, reports in humans are largely anecdotal and this hypothesis remains to be tested directly and systematically using preclinical models. We previously demonstrated in male rats that Meth administration, when followed immediately by mating behavior (here termed concurrent Meth and sex) resulted in maladaptive sex-seeking behavior or hypersexuality [19][20][21]. The current study directly tests the hypothesis that Meth taken concurrently with sexual behavior will increase the vulnerability to develop drug addiction in male rats.…”

Section: Introductionmentioning

confidence: 81%

Drug-taking in a socio-sexual context enhances vulnerability for addiction in male rats

Kuiper

Beloate

Dupuy

et al. 2018

Neuropsychopharmacol

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Vulnerability to develop addiction is influenced by numerous factors, including social behavior. Specifically, in human users, drug taking in a socio-sexual context appears to enhance further drug-seeking behavior. Users report heightened sexual pleasure as a motivation for further drug use and display risk behaviors even when tested in drug-free state. Here, using a preclinical model of limited voluntary drug use in rats, the hypothesis was tested that methamphetamine (Meth)-taking concurrently with socio-sexual experience increases vulnerability to addiction. Male Sprague Dawley rats were socially housed and underwent limited-access Meth self-administration (maximum 1 mg/kg/session). Meth-taking was either concurrent or non-concurrent with sexual behavior: concurrent animals were mated with a receptive female immediately after each session, while non-concurrent animals gained equivalent sexual experience the week prior. Next, drug-seeking behaviors were measured during cue reactivity, extinction, and reinstatement sessions using different extinction and reinstatement protocols in 4 separate studies. Both groups equally acquired Meth self-administration and did not differ in total Meth intake. However, drug-seeking behavior was significantly higher in concurrent animals during cue reactivity tasks, extinction sessions, and cue-or Meth-induced reinstatement tests. In addition, sexual behavior in the absence of Meth triggered reinstatement of drug-seeking in concurrent animals. These results indicate that Meth-taking in a socio-sexual context significantly enhances vulnerability for drug addiction in male rats. This preclinical paradigm of drug self-administration concurrent with socio-sexual behavior provides a useful model for studying the underlying neurobiology of socially driven vulnerability to drug addiction.Neuropsychopharmacology (2019) 44:503-513; https://doi.

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Section: Introductionmentioning

confidence: 81%

Drug-taking in a socio-sexual context enhances vulnerability for addiction in male rats

Kuiper

Beloate

Dupuy

et al. 2018

Neuropsychopharmacol

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show abstract

“…While the current study focuses on female sexual behaviors, recent studies in male rats show that repeated METH treatment leads to compulsive sexual behavior (Frohmader et al, 2010) and an increase in sexual reward, as measured by conditioned placed preference (Frohmader et al, 2011). Taken together with the current set of studies, our data demonstrate that the rodent model can be used to further examine the molecular and neurobiological mechanisms of METH’s effects on sexual behaviors.…”

Section: Discussionmentioning

confidence: 99%

Methamphetamine-enhanced female sexual motivation is dependent on dopamine and progesterone signaling in the medial amygdala

Holder

Veichweg

Mong

2015

Hormones and Behavior

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Methamphetamine (METH) is a psychomotor stimulant strongly associated with increases in sexual drive and impulsive sexual behaviors that often lead to unsafe sexual practices. In women METH users, such practices have been associated with increases in unplanned pregnancies and sexually transmitted diseases. Despite this significant heath concern, the neural mechanisms underlying this drug-sex association are not known. We previously established a rodent model of METH-facilitated female sexual behavior in which estradiol and progesterone interact with METH to increase motivational components of female behavior and neuronal activation in the posterodorsal medial amygdala (MePD) (Holder et al., 2010; Holder and Mong, 2010). The current study more directly examines the mechanisms underlying the drug-sex interaction. Here, we hypothesize that METH-induced increases in MePD dopamine signaling bridge the METH-hormone interaction. In support of this hypothesis, we found that excitotoxic lesions targeted to the MePD attenuated the METH-induced increases in proceptive behavior. Furthermore, infusion of a D1 agonist into the MePD increased proceptive behavior, while infusion of a D1 antagonist blocked the ability of METH to increase proceptive behaviors. Additionally, we found that METH-treatment increased progesterone receptor (PR)- immunoreactivity in the MePD, suggesting an interaction between dopamine and progesterone signaling. Indeed, infusions of the PR antagonist, RU486, prevented METH-induced increases in sexual behavior. Thus, taken together, the current findings suggest dopamine in the MePD modulates enhanced sexual motivation via an amplification of progesterone signaling and contributes to a better understanding of the neurobiology of drug-enhanced sexual behaviors.

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“…Specifically, cocaine exposure leads to AMPA receptor current changes on NAc medium spiny neurons that are dependent on NMDA receptor activation (Ungless et al, 2001), and Amph behavioral sensitization is prevented by co-administration (systemic) of MK 801 (Wolf and Jeziorski, 1993). Sex behavior also results in locomotor sensitization by Amph (Pitchers et al, 2010a(Pitchers et al, , 2012 and methamphetamine (Frohmader et al, 2011), but it is Quantitative data of cFos expression in NAc core (E) and shell (F) from males that received intra-NAc saline (light gray bars, n ¼ 5), 0.5 ml MK 801 (dark gray bars, n ¼ 6) or 1 ml MK 801 (black bars, n ¼ 5) prior to mating or no mating (white bars, n ¼ 12; 4 from each drug group). Data are presented as mean ± SEM.…”

Section: Discussionmentioning

confidence: 99%

“…CPP for Amph was conducted as previously described (Pitchers et al, 2010a(Pitchers et al, , 2013Frohmader et al, 2011). The apparatus consists of two main chambers separated by a smaller middle chamber, each distinguishable by visual and tactile cues (Med Associates, St. Albans, VT).…”

Section: D-amphetamine Conditioned Place Preferencementioning

confidence: 99%

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Nucleus accumbens NMDA receptor activation regulates amphetamine cross-sensitization and deltaFosB expression following sexual experience in male rats

et al. 2016

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Concurrent Exposure to Methamphetamine and Sexual Behavior Enhances Subsequent Drug Reward and Causes Compulsive Sexual Behavior in Male Rats

Cited by 27 publications

References 84 publications

Drug-taking in a socio-sexual context enhances vulnerability for addiction in male rats

Drug-taking in a socio-sexual context enhances vulnerability for addiction in male rats

Methamphetamine-enhanced female sexual motivation is dependent on dopamine and progesterone signaling in the medial amygdala

Nucleus accumbens NMDA receptor activation regulates amphetamine cross-sensitization and deltaFosB expression following sexual experience in male rats

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