Imaging the Conditioned Behavioral Effects of Methamphetamine in Rodents

Abstract

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 cueelicited craving in rodents and humans, we used behavioral neuroimaging with 2-[ 18 F]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.

Assessment of IP injection of [18F]fallypride for behavioral neuroimaging in rats

“…Interestingly, the behavioral-compatible paradigm of IP [ 18 F]FDG injection with a conscious uptake period prior to ketamine/xylazine anesthesia results in significantly higher glucose utilization compared to when [ 18 F]FDG is administered to an anesthetized animal (Schiffer et al, 2007). This is suggestive that the awake uptake period is key for collecting functional data with [ 18 F]FDG PET, and recent data suggests that this method is sensitive enough to capture changes in metabolism during behavior (Carrion et al, 2009;Mirrione et al, 2006). Ketamine/xylazine anesthesia was also used in two PET studies that documented pharmacologically and behaviorally induced increases in dopamine in awake animals after IP injection of the D 2 antagonist, [ 11 C]raclopride (Patel et al, 2008;Schiffer et al, 2009).…”

“…Recently, the scope and relevance of small animal PET imaging were expanded by the first reports of behavioral neuroimaging with [ 18 F]FDG and [ 11 C]raclopride (Carrion et al, 2009;Patel et al, 2008;Schiffer et al, 2007Schiffer et al, , 2009). Although the [ 11 C]raclopride data documenting changes in striatal dopamine during behavior are exciting, the long half-life of [ 18 F] tracers would permit more flexibility in choice of behavioral paradigms.…”

“…In order to administer radiotracer to awake animals in a non-invasive manner (i.e., without an implanted venous catheter or tail vein injection), intraperitoneal (IP) injections of tracer would be required. Indeed, PET scanning after IP injection of [ 18 F]FDG in awake animals has proven useful for assessment of relative glucose metabolism (Carrion et al, 2009;Schiffer et al, 2007). The primary objective of this study was to determine whether IP injections of FAL would produce equivalent data to that from PET scans performed with an intravenous (IV) tail vein injection.…”

Imaging Sex Differences in Regional Brain Metabolism during Acute Opioid Withdrawal

“…Images were overlaid onto an anatomical cryostat template with increases set as hot (red-yellow), and metabolic decreases set as winter (blue-green). The color scale used represents all T distributions achieving statistical significance [27–29]. All corresponding brain areas are significant at a value of p ≤ 0.001 (corrected) with a cluster-extent threshold of k=0 voxels.…”

Brain Glucose Metabolism and Dopamine Transporters Change in Addiction and Environmental Cue-Induced Memory

“…Therefore, association between cues and the rewarding effects of drugs is one of the main reasons for drug relapse. A feelings of craving and conditioned physiological response always occur when abstinent drug abusers have cues of the rewarding effects of the used drugs [2]. Craving can't be measured directly by animal models, although we knew drug abuse strengthened by conditional associations with environmental cues.…”