Non-genetic factors that influence methamphetamine intake in a genetic model of differential methamphetamine consumption
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ORIGINAL INVESTIGATION
Non-genetic factors that influence methamphetamine intake in a genetic model of differential methamphetamine consumption A. M. Stafford 1 & C. Reed 1 & T. J. Phillips 1,2 Received: 26 March 2020 / Accepted: 17 July 2020 # This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply 2020
Abstract Rationale Genetic and non-genetic factors influence substance use disorders. Our previous work in genetic mouse models focused on genetic factors that influence methamphetamine (MA) intake. The current research examined several non-genetic factors for their potential influence on this trait. Objectives We examined the impact on MA intake of several non-genetic factors, including MA access schedule, prior forced MA exposure, concomitant ethanol (EtOH) access, and gamma-aminobutyric acid type B (GABAB) receptor activation. Selectively bred MA high drinking (MAHDR) and low drinking (MALDR) mice participated in this research. Results MAHDR, but not MALDR, mice increased MA intake when given intermittent access, compared with continuous access, with a water choice under both schedules. MA intake was not altered by previous exposure to forced MA consumption. Male MAHDR mice given simultaneous access to MA, EtOH, and an EtOH+MA mixture exhibited a strong preference for MA over EtOH and EtOH+MA; MA intake was not affected by EtOH in female MAHDR mice. When independent MAHDR groups were given access to MA, EtOH, or EtOH+MA vs. water in each case, MA intake was reduced in the water vs. EtOH+MA group, compared with the water vs. MA group. The GABAB receptor agonist R(+)-baclofen (BAC) not only reduced MA intake but also reduced water intake and locomotor activity in MAHDR mice. There was a residual effect of BAC, such that MA intake was increased after termination of BAC treatment. Conclusions These findings demonstrate that voluntary MA intake in MAHDR mice is influenced by non-genetic factors related to MA access schedule and co-morbid EtOH exposure. Keywords Amphetamine . Ethanol . Self administration . GABA . Substance use disorder . Addiction
Introduction Genetic and non-genetic factors and their interactions influence substance use disorders (SUDs). Data from adult twin studies have demonstrated that SUDs are heritable (Goldman et al. 2005; Kendler et al. 1999, 2000; Tsuang et al. 1996; van den Bree et al. 1998), and that large numbers of genes contribute to psychiatric disorders like SUDs (Dick et al. 2010; Manolio et al. 2009). Non-genetic factors that contribute can be intrinsic (age, sex, co-morbid SUD, or other mental illness), * T. J. Phillips [email protected] 1
Department of Behavioral Neuroscience and Methamphetamine Abuse Research Center, Oregon Health & Science University, Portland, OR, USA
2
Veterans Affairs Portland Health Care System, Portland, OR, USA
extrinsic (drug availability, peer and parental influences), or related to characteristics of the drug (pharmacokinetics, route of administration) (Ahmed et al. 2020; Ducci and Gol
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