The Effects of Maternal Separation on Adult Methamphetamine Self-Administration, Extinction, Reinstatement, and MeCP2 Immunoreactivity in the Nucleus Accumbens
Open Access
- 1 January 2013
- journal article
- research article
- Published by Frontiers Media SA in Frontiers in Psychiatry
- Vol. 4, 55
- https://doi.org/10.3389/fpsyt.2013.00055
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.This publication has 52 references indexed in Scilit:
- DNA methylation as a risk factor in the effects of early life stressBrain, Behavior, and Immunity, 2011
- Chronic alcohol neuroadaptation and stress contribute to susceptibility for alcohol craving and relapsePharmacology & Therapeutics, 2011
- Neonatal maternal separation exacerbates the reward-enhancing effect of acute amphetamine administration and the anhedonic effect of repeated social defeat in adult ratsNeuroscience, 2010
- MeCP2 in the nucleus accumbens contributes to neural and behavioral responses to psychostimulantsNature Neuroscience, 2010
- Anti-craving effects of environmental enrichmentInternational Journal of Neuropsychopharmacology, 2009
- Methamphetamine toxicity and messengers of deathBrain Research Reviews, 2009
- Lasting Epigenetic Influence of Early-Life Adversity on the BDNF GeneBiological Psychiatry, 2009
- Frequency of maternal licking and grooming correlates negatively with vulnerability to cocaine and alcohol use in ratsPharmacology Biochemistry and Behavior, 2008
- Epigenetic mechanisms in drug addictionTrends in Molecular Medicine, 2008
- Maternal separation alters drug intake patterns in adulthood in ratsBiochemical Pharmacology, 2007