Background: Individual variation exists with respect to the development and severity of drug addiction and this individual variability reflects a combination of environmental and genetic factors. However, the biochemical correlates of addiction vulnerability/resiliency are severely understudied, particularly to the highly addictive psychomotor stimulant methamphetamine (MA). Even in presumably genetically homogeneous populations of C57BL/6J (B6) mice, marked variability exists with respect to the capacity of repeated MA (4X2 mg/kg) to elicit place-conditioning, an index of MA’s motivational/affective valence. While approximately 50% of B6 mice exhibit a conditioned-preference (CPP) for a MA-paired environment, approximately 12% show conditioned aversion (CPA), and the remaining mice exhibit ambivalence or no conditioned response (Neutral).

Methods: We tested the predictive validity of studying inbred B6 mice under simple place-conditioning procedures as a high-throughput strategy for the study of MA addiction vulnerability/resiliency, by correlating phenotype with MA-induced locomotor activity, by assaying CPP-, Neutral- and CPA-B6 mice in a place-conditioning version of the extinction/reinstatement paradigm, as well as an oral MA self-administration paradigm (10-40 mg/L). We also tested the construct validity of this model by examining for phenotypic differences in the expression of glutamate-related proteins within the nucleus accumbens core.

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