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: Addiction; Amphetamine; Ethanol; GABA; Self administration; Substance use disorder.