Chronic opiate exposure in the male rat adversely affects fertility

Cicero, Theodore J.; Davis, L.A; LaRegina, Marie C.; Meyer, Edward R.; Schlegel, M

doi:10.1016/s0091-3057(01)00751-1

Cited by 38 publications

(30 citation statements)

References 18 publications

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“…A distinction between drug and natural reward occurred in females, as oxytocin only decreased meth taking, but not sucrose taking, during the PR. Interestingly, females in general demonstrated greater motivated meth taking, which is in line with previous self-administration studies with meth (Roth and Carroll, 2004), cocaine (Roberts et al, 1989), heroin (Cicero et al, 2002), and alcohol (Peters et al, 2013). While we found the ability of oxytocin to reduce motivation to obtain meth was specific to females, a previous study showed that oxytocin (1 mg/kg) decreased responding on a similar PR task in male rats (Carson et al, 2010a).…”

Section: Discussionsupporting

confidence: 89%

Sex differences in methamphetamine seeking in rats: Impact of oxytocin

Cox

Young

See

et al. 2013

Psychoneuroendocrinology

141

158

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Previous evidence in an animal model of drug self-administration and drug seeking showed that acute oxytocin decreased methamphetamine (meth) seeking in male rats, suggesting potential clinical efficacy for the treatment of psychostimulant addiction. However, based on the well-established role of oxytocin in reproduction and pair bond formation, it is important to know how this effect extrapolates to females. Here, we tested whether oxytocin (1 mg/kg, IP) would decrease meth seeking in female rats across various stages of the estrous cycle (Experiment 1). Freely cycling Long Evans female rats self-administered meth (IV) in 2-h daily sessions, followed by daily extinction sessions. Following extinction, rats received oxytocin (0, 0.3, or 1 mg/kg, IP) 30 min before a meth priming injection (1 mg/kg, IP) to assess reinstatement of meth seeking. Next, we examined the effects of oxytocin on motivated meth- and sucrose-taking and seeking in male and female rats. In separate experiments, males and females self-administered meth (Experiment 2) or sucrose (Experiment 3) until responding was stabilized along a fixed ratio (FR) 5 schedule of reinforcement. Subsequently, rats received either oxytocin or vehicle prior to self-administration along a progressive ratio (PR) schedule of reinforcement. Rats were subsequently tested for cue-, meth-, and stress-induced reinstatement after pretreatment with oxytocin or vehicle. While oxytocin reduced meth seeking in females, we found that estrous cycle stage (as determined from vaginal cytology) did not influence meth-primed reinstatement or the ability of oxytocin to decrease reinstatement of meth seeking. Oxytocin reduced PR responding for meth only in females. Females responded more than males during cue-induced reinstatement of meth and sucrose seeking, and oxytocin reduced this responding only in meth females. In both sexes, oxytocin attenuated meth seeking in response to a meth prime and yohimbine (a pharmacological stressor). The results suggest that oxytocin may have efficacy as a treatment of meth addiction in both sexes; however, females may show greater response to oxytocin treatment for the prevention of relapse.

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Section: Discussionsupporting

confidence: 89%

Sex differences in methamphetamine seeking in rats: Impact of oxytocin

Cox

Young

See

et al. 2013

Psychoneuroendocrinology

141

158

View full text Add to dashboard Cite

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“…Significant reduction of spermatozoid motility is observed following incubation with morphine (but not in the presence of naloxone, a μ-1 antagonist), suggesting a possible role of μ-1 agonists in regulation of sperm functioning. 13 These findings are consistent with earlier animal studies, which showed that chronic opioid administration adversely affected male rat fertility and produced a number of deficits in their offspring, 14 and it also dramatically reduced the size and secretory activity of the rat's secondary sex organs. 15 As methylation of DNA during genesis and development of parental gametes has a key role on this process, analyses of gametic DNA methylation or sex-specific patterns of transmission can supply evidence for heritable epigenetic features.…”

Section: Introductionsupporting

confidence: 89%

Elevated levels of DNA methylation at the OPRM1 promoter in blood and sperm from male opioid addicts

Chorbov¹,

Todorov²,

Lynskey³

et al. 2018

J of Opioid Management

113

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Objective The OPRM1 gene was studied for DNA methylation in opioid dependence and possible paternal contribution to epigenetic inheritance of altered methylation profiles. Participants and methods DNA was extracted from blood and sperm from 13 male opioid addicts and 21 male control subjects. DNA methylation was determined by pyrosequencing in 24 CpG sites at the OPRM1 promoter region. Results The authors found significantly increased overall methylation in blood DNA from addicted subjects (Kruskal-Wallis [K-W] p = 0.013) Seven CpG sites showed significantly hypermethylated blood DNA from cases when compared with blood DNA controls (p < 0.05 at CpGs 5, 9, 10, 11, 18, 23, and 24). In sperm-derived DNA from addicts, the methylation was significantly increased at CpG 2 (p = 0.012), and overall methylation did not reach significant difference ( K-W p = 0.523). Conclusions Increased DNA methylation in the OPRM1 gene is associated with opioid dependence. Hypermethylated CpG sites located in OPRM1 promoter may potentially block the binding of Sp1 and other transcription activators, thus leading to OPRM1 silencing. The increased DNA methylation in sperm may suggest a way of epigenetic heritability of opioid abuse or dependence phenotypes.

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“…Decreased blastocyst cell number is reflective of reduced viability (26,29,34), thus we transferred morphologically similar blastocysts from both groups, with paternal obesity significantly decreasing embryo implantation and the development of viable fetuses by day 18 of pregnancy. A relationship between paternal obesity and early pregnancy loss has not previously been reported; however, other paternal exposures, including opiate use and tamoxifen administration, have also impaired early pregnancy survival (35)(36)(37).…”

Section: Discussionmentioning

confidence: 91%