Abstract
The maternal separation (MS) paradigm is an animal model of early life stress. Animals subjected to MS during the first 2 weeks of life display altered behavioral and neuroendocrinological stress responses as adults. MS also produces altered responsiveness to and self-administration (SA) of various drugs of abuse including cocaine, ethanol, and amphetamine. However, no studies have yet examined the effects of MS on methamphetamine (METH) SA. This study was performed to examine the effects of MS on the acquisition of METH SA, extinction, and reinstatement of METH-seeking behavior in adulthood. Given the known influence of early life stress and drug exposure on epigenetic processes, we also investigated group differences in levels of the epigenetic marker methyl CpG binding protein 2 (MeCP2) in the nucleus accumbens (NAc) core. Long–Evans pups and dams were separated on postnatal days (PND) 2–14 for either 180 (MS180) or 15 min (MS15). Male offspring were allowed to acquire METH SA (0.05 mg/kg/infusion) in 15 2-h daily sessions starting at PND67, followed by extinction training and cue-induced reinstatement of METH-seeking behavior. Rats were then assessed for MeCP2 levels in the NAc core by immunohistochemistry. The MS180 group self-administered significantly more METH and acquired SA earlier than the MS15 group. No group differences in extinction or cue-induced reinstatement were observed. MS15 rats had significantly elevated MeCP2-immunoreactive cells in the NAc core as compared to MS180 rats. Together, these data suggest that MS has lasting influences on METH SA as well as epigenetic processes in the brain reward circuitry.
Highlights
Methamphetamine (METH) is an extremely potent and highly addictive psychostimulant and neurotoxic drug (Xie and Miller, 2009)
METH SELF-ADMINISTRATION A total of n = 4 animals were removed from the MS15 and MS180 groups respectively due to loss of catheter patency
No group differences in the total number of inactive lever presses were observed [F (1,17) = 38.76, p = 0.425]. In both rearing conditions we noted a time-dependent increase in inactive lever pressing across SA sessions, and we attribute this to be a result of non-specific motor activity that resulted from increasing level of METH SA
Summary
Methamphetamine (METH) is an extremely potent and highly addictive psychostimulant and neurotoxic drug (Xie and Miller, 2009). METH abuse has many detrimental consequences for the individual and for society as a whole. METH abuse has been identified as both a strong risk factor for violence and high-risk sexual behaviors. In one study of a population between the ages of 18 and 25, 34.9% self-reported violent behavior while under the influence of METH, such as domestic violence, gang-related violence, and random acts of violence (Sommers et al, 2006). Individuals on METH often engage in unprotected vaginal and anal sex and have sex with multiple partners (Springer et al, 2007). It is apparent that chronic METH use has a multitude of deleterious effects on both the users and society as a whole
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