Stress changes amphetamine response, D2 receptor expression and epigenetic regulation in low-anxiety rats

Karolina Kołosowska; Aleksandra Gawryluk; Aleksandra Wisłowska-Stanek; Monika Liguz-Lęcznar; Katarzyna Hetmańczyk; Agnieszka Ługowska; Alicja Sobolewska; Anna Skórzewska; Marek Gryz; Małgorzata Lehner

doi:10.1016/j.pnpbp.2019.04.009

Stress changes amphetamine response, D2 receptor expression and epigenetic regulation in low-anxiety rats

Prog Neuropsychopharmacol Biol Psychiatry. 2019 Jul 13:93:256-268. doi: 10.1016/j.pnpbp.2019.04.009. Epub 2019 Apr 22.

Affiliations

¹ Department of Neurochemistry, Institute of Psychiatry and Neurology, 9 Sobieskiego Street, 02-957 Warsaw, Poland. Electronic address: kkolosow@tlen.pl.
² Department of Molecular and Cellular Neurobiology, Nencki Institute of Experimental Biology, Polish Academy of Sciences, 3 Pasteur Street, 02-093 Warsaw, Poland.
³ Department of Experimental and Clinical Pharmacology, Medical University of Warsaw, Centre For Preclinical Research and Technology (CePT), 1B Banacha Street, 02-097 Warsaw, Poland.
⁴ Department of Genetics, Institute of Psychiatry and Neurology, 9 Sobieskiego Street, 02-957 Warsaw, Poland.
⁵ Department of Neurochemistry, Institute of Psychiatry and Neurology, 9 Sobieskiego Street, 02-957 Warsaw, Poland.

PMID: 31022425
DOI: 10.1016/j.pnpbp.2019.04.009

Abstract

The aim of this study was to assess the influence of chronic restraint stress on amphetamine (AMPH)-related appetitive 50-kHz ultrasonic vocalisations (USVs) in rats differing in freezing duration in a contextual fear test (CFT), i.e. HR (high-anxiety responsive) and LR (low-anxiety responsive) rats. The LR and the HR rats, previously exposed to an AMPH binge experience, differed in sensitivity to AMPH's rewarding effects, measured as appetitive vocalisations. Moreover, chronic restraint stress attenuated AMPH-related appetitive vocalisations in the LR rats but had no influence on the HR rats' behaviour. To specify, the restraint LR rats vocalised appetitively less in the AMPH-associated context and after an AMPH challenge than the control LR rats. This phenomenon was associated with a decrease in the mRNA level for D2 dopamine receptor in the amygdala and its protein expression in the basal amygdala (BA) and opposite changes in the nucleus accumbens (NAc) - an increase in the mRNA level for D2 dopamine receptor and its protein expression in the NAc shell, compared to control conditions. Moreover, we observed that chronic restraint stress influenced epigenetic regulation in the LR and the HR rats differently. The contrasting changes were observed in the dentate gyrus (DG) of the hippocampus - the LR rats presented a decrease, but the HR rats showed an increase in H3K9 trimethylation. The restraint LR rats also showed higher miR-494 and miR-34c levels in the NAc than the control LR group. Our study provides behavioural and biochemical data concerning the role of differences in fear-conditioned response in stress vulnerability and AMPH-associated appetitive behaviour. The LR rats were less sensitive to the rewarding effects of AMPH when previously exposed to chronic stress that was accompanied by changes in D2 dopamine receptor expression and epigenetic regulation in mesolimbic areas.

Keywords: Amphetamine binge; Chronic restraint stress; Epigenetics; Individual differences; Mesolimbic dopaminergic system; miRNAs.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amphetamine / pharmacology*
Animals
Anxiety / metabolism
Anxiety / physiopathology
Dentate Gyrus / metabolism
Disease Models, Animal
Epigenesis, Genetic* / drug effects
Epigenesis, Genetic* / physiology
Fear / drug effects
Hippocampus / metabolism
Male
Rats
Rats, Wistar
Real-Time Polymerase Chain Reaction
Receptors, Dopamine D2 / metabolism*
Stress, Psychological / metabolism*
Stress, Psychological / physiopathology

Substances

Receptors, Dopamine D2
Amphetamine