title: Sign-trackers have elevated myo-inositol in the nucleus accumbens and ventral hippocampus following Pavlovian conditioned approach.
abstract: 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 (1H-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), a1H-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.
authors.affiliation: Neuroscience Graduate Program, University of Michigan, Ann Arbor, Michigan, USA.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Fitzpatrick
authors.affiliation: Department of Psychiatry and Behavioral Neurosciences, Wayne State University School of Medicine, Detroit, Michigan, USA.
authors.forename: Shane A
authors.initials: SA
authors.lastname: Perrine
authors.affiliation: Department of Anesthesiology, Wayne State University School of Medicine, Detroit, Michigan, USA.
authors.forename: Farhad
authors.initials: F
authors.lastname: Ghoddoussi
authors.affiliation: Department of Psychiatry and Behavioral Neurosciences, Wayne State University School of Medicine, Detroit, Michigan, USA.|Department of Anesthesiology, Wayne State University School of Medicine, Detroit, Michigan, USA.
authors.forename: Matthew P
authors.initials: MP
authors.lastname: Galloway
authors.affiliation: Neuroscience Graduate Program, University of Michigan, Ann Arbor, Michigan, USA.|Department of Psychiatry, University of Michigan, Ann Arbor, Michigan, USA.
authors.forename: Jonathan D
authors.identifier: http://orcid.org/0000-0002-3530-4544
authors.initials: JD
authors.lastname: Morrow
keywords: Pavlovian conditioned approach; myo-inositol; nucleus accumbens; proton-magnetic resonance spectroscopy; sign-tracking; ventral hippocampus