Imaging the Conditioned Behavioral Effects of Methamphetamine in Rodents

Cue-elicited craving is modeled in rats using the conditioned place preference (CPP) paradigm, however it is not known whether this CPP produces a pattern of brain activations homologous to those reported in humans. To test the hypothesis that similar neural circuits underlie cue-elicited craving in rodents and humans, we used behavioral neuroimaging with 2-[¹⁸F]fluoro-2-deoxy-d-glucose (FDG) and positron emission tomography (PET) in freely moving rats during the expression of place preference to methamphetamine (METH). Statistical parametric mapping (SPM) correlated preference with regional changes in brain activation. We observed increased relative FDG uptake compared to baseline in the cerebellum, thalamus, frontal, sensory and motor cortices. There were significant decreases in the insular cortex and throughout the hippocampus. Covariate analysis revealed circuitry in the dorsal and ventral striatum, cingulate gyrus and amygdala where relative FDG uptake correlated with individual differences in preference. These findings demonstrate a strong overlap in those areas activated by the expression of place preference in rodents and distinct patterns of brain activation observed with expectancy and cue-induced craving in humans. We conclude that neuroimaging in animals enriches, and is enriched by, the field of Pavlovian conditioning as well as other fields of behavioral science.