Selective breeding for magnitude of methamphetamine-induced sensitization alters methamphetamine consumption

Abstract

Rationale Genetically determined differences in susceptibility to drug-induced sensitization could be related to risk for drug consumption. Objectives Studies were performed to determine whether selective breeding could be used to create lines of mice with different magnitudes of locomotor sensitization to methamphetamine (MA). MA sensitization (MASENS) lines were also examined for genetically correlated responses to MA. Methods Beginning with the F2 cross of C57BL/6J and DBA/2J strains, mice were tested for locomotor sensitization to repeated injections of 1 mg/kg MA and bred based on magnitude of sensitization. Five selected offspring generations were tested. All generations were also tested for MA consumption, and some were tested for dose-dependent locomotor-stimulant responses to MA, consumption of saccharin, quinine, and potassium chloride as a measure of taste sensitivity, and MA clearance after acute and repeated MA. Results Selective breeding resulted in creation of two lines [MA high sensitization (MAHSENS) and MA low sensitization (MALSENS)] that differed in magnitude of MA-induced sensitization. Initially, greater MA consumption in MAHSENS mice reversed over the course of selection so that MALSENS mice consumed more MA. MAHSENS mice exhibited greater sensitivity to the acute stimulant effects of MA, but there were no significant differences between the lines in MA clearance from blood. Conclusions Genetic factors influence magnitude of MA-induced locomotor sensitization and some of the genes involved in magnitude of this response also influence MA sensitivity and consumption. Genetic factors leading to greater MA-induced sensitization may serve a protective role against high levels of MA consumption.

Methamphetamine Addiction Vulnerability: The Glutamate, the Bad, and the Ugly

“…Although MA-preference/taking can relate to sensitivity to the drug’s psychomotor-activating effects (16,30,31), within the large sample of B6 mice tested, group differences in spontaneous or MA-induced locomotor activity were not detected (Suppl. Table S1).…”

Methamphetamine causes anorexia in <i>Drosophila melanogaster</i>, exhausting metabolic reserves and contributing to mortality

“…Naïve flies strongly preferred to eat unadulterated diet over that containing MA (Fig. 9A), which is reported to have a bitter taste (Scibelli et al, 2011), revealing that flies can detect MA and find it aversive. When given the choice between SOA, a bitter non-toxic tastant, and MA, flies showed no preference for either compound and generally ate much less than when unadulterated diet was available (Figs.…”

Nine Generations of Selection for High and Low Nicotine Intake in Outbred Sprague–Dawley Rats

“…Selective breeding has been used for generating rodent models with various sensitivities to methamphetamine, opiates, or alcohol or related bio-behavioral traits (Carlson et al 1996; Scibelli et al 2011; Li et al 1993). However, phenotypic selection for differences in nicotine-related physiological changes and behaviors has rarely been done.…”