Sign-trackers have elevated myo-inositol in the nucleus accumbens and ventral hippocampus following Pavlovian conditioned approach.

Pavlovian conditioned approach (PCA) is a behavioral procedure that can be used to assess individual differences in the addiction vulnerability of drug-naïve rats and identify addiction vulnerability factors. Using proton magnetic resonance spectroscopy (1 H-MRS) ex vivo, we simultaneously analyzed concentrations of multiple neurochemicals throughout the mesocorticolimbic system 2 weeks after PCA training in order to identify potential vulnerability factors to addiction in drug-naïve rats for future investigations. Levels of myo-inositol (Ins), a 1 H-MRS-detectable marker of glial activity/proliferation, were increased in the nucleus accumbens (NAc) and ventral hippocampus, but not dorsal hippocampus or medial prefrontal cortex, of sign-trackers compared to goal-trackers or intermediate responders. In addition, Ins levels positively correlated with PCA behavior in the NAc and ventral hippocampus. Because the sign-tracker phenotype is associated with increased drug-seeking behavior, these results observed in drug-naïve rats suggest that alterations in glial activity/proliferation within these regions may represent an addiction vulnerability factor. Sign-tracking rats preferentially approach reward cues during Pavlovian conditioning, while goal-trackers instead approach the location of impending reward. Sign-trackers are also more prone to cue-induced drug-seeking behavior. We used magnetic resonance spectroscopy to show that myo-inositol levels are higher in the ventral hippocampus and nucleus accumbens of sign-trackers relative to goal-trackers. Thus, elevated myo-inositol may be a vulnerability factor for addiction.