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Neuroscience letters
09 14, 2018;683 125-130.

Methamphetamine alters DNMT and HDAC activity in the posterior dorsal medial amygdala in an ovarian steroid-dependent manner.

Sarah A Rudzinskas, Jessica A Mong
Author Information
  1. Sarah A Rudzinskas: Program in Neuroscience, University of Maryland, Baltimore, School of Medicine, Baltimore, MD, 21201, United States; Department of Pharmacology, University of Maryland, Baltimore, School of Medicine, Baltimore, MD, 21201, United States. Electronic address: srudzinskas@umaryland.edu.
  2. Jessica A Mong: Program in Neuroscience, University of Maryland, Baltimore, School of Medicine, Baltimore, MD, 21201, United States; Department of Pharmacology, University of Maryland, Baltimore, School of Medicine, Baltimore, MD, 21201, United States.
PMID: 29944893 DOI: 10.1016/j.neulet.2018.06.042

Abstract

Methamphetamine (Meth) is a psychomotor stimulant associated with increased sexual drive and risky sexual behaviors in both men and women. Females are comparatively understudied, despite the fact that are just as likely as men to use methamphetamine. Importantly, Meth-associated sexual behaviors put female-users at a greater risk for unplanned pregnancies, and increase the risk of psychiatric co-morbidities such as depression. Our work in a rodent model has demonstrated that in the presence of the ovarian steroids, estradiol (EB) and progesterone (P), methamphetamine facilitates the activation of neurons of in the Medial Amygdala (MePD) and Ventromedial Nucleus of the Hypothalamus (VMN), nuclei that are integral to female sexual behavior. As methamphetamine has been previously associated with epigenetic changes in males, we hypothesized that methamphetamine may facilitate sexual motivation in females by modulating the amount of epigenetic enzymatic activity in the VMN and MePD. To test this hypothesis, histone deacetylase (HDAC) and DNA methyltransferase (DNMT) activity was quantitated in both the VMN and MePD in the presence and absence of methamphetamine in femalerats who were ovariectomized (OVX), or OVXed and hormone replaced with EB + P. DMNT1 and DNMT3B protein levels were also assessed. Our results show that methamphetamine alters DNMT and HDAC activity in the MePD in an ovarian steroid-dependent fashion. Both methamphetamine alone and EB + P alone significantly reduce DNMT enzymatic activity in an OVX female, but do not further decrease activity when both are given in combination. In contrast, no changes in HDAC or DNMT activity were seen in the VMN regardless of treatment, but the amount of DNMT3b after methamphetamine was significantly altered depending on the presence or absence of ovarian steroids. Taken together, these results support the hypothesis that methamphetamine induces change on an epigenetic level in female rats in both a hormone and nucleus dependent manner, and suggests epigenetic changes may play a role in methamphetamine's mechanism to facilitate the sexual motivation.

Keywords

DNMTs Epigenetics Female sexual motivation HDACs Medial amygdala Methamphetamine Methylation Sex behavior

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Grants

  1. R01 DA030517/NIDA NIH HHS

MeSH Term

Animals
Central Nervous System Stimulants
Corticomedial Nuclear Complex
DNA (Cytosine-5-)-Methyltransferase 1
DNA (Cytosine-5-)-Methyltransferases
Estradiol
Female
Histone Deacetylases
Methamphetamine
Ovary
Progesterone
Rats
Rats, Sprague-Dawley
Sexual Behavior, Animal
DNA Methyltransferase 3B

Chemicals

Central Nervous System Stimulants
estradiol 3-benzoate
Methamphetamine
Progesterone
Estradiol
DNA (Cytosine-5-)-Methyltransferase 1
DNA (Cytosine-5-)-Methyltransferases
Dnmt1 protein, rat
Histone Deacetylases
Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't
Article has an altmetric score of 1

Word Cloud

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