Divergent Brain Adaptations in Addicted-Like and Non-Addicted-Like Rats after Prolonged Cocaine Self-Administration: A Multimodal Neuroimaging Study.

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Cannella N1, Cosa-Linan A1, Röscher M3, Takahashi TT1, Weber-Fahr W2, Wängler B3, Noori HR1, Spanagel R1.

1Institute of Psychopharmacology and 2Research Group Translational Imaging, Central Institute of Mental Health, Medical Faculty Mannheim / Heidelberg University, Germany;
3Department of Clinical Radiology and Nuclear Medicine, Medical Faculty Mannheim/Heidelberg University, Mannheim, Germany

Cocaine dependence develops in a subset of drug users vulnerable to addiction, while the majority of drug users maintain control over cocaine. Here, we studied the differences in the brain functional organization, structure, and activity between rats that maintained control over drug use (0crit) and those that developed addiction-like behaviour (3crit), according to the 0/3crit model of addiction.
We analysed the effective connectivity by the spectral inversion of a dynamic causal model including connections between three well-known nodes involved in the development of addictive behaviour (amygdala, prelimbic cortex and nucleus accumbens). In 3crit rats we found an altered connectivity within this network respect to 0crit that showed similar connectivity to cocaine-naïve rats. Interestingly, administration of a cocaine challenge did not modify the structure of the causal network in 0crit and cocaine-naïve rats, while it modified the structure of the causal network in 3crit.
Grey matter volume (GMV) was analysed by Voxel Based Morphometry. A regression analysis of the relationship between GMV and three sub-dimensions of addiction-like behaviour such as high motivation for cocaine taking, compulsivity, and persistent cocaine seeking, revealed an opposed relation between GMV and each of the three addiction sub-dimensions in 0crit and 3crit in the absence of significant group effects.
Manganese-enhanced MRI and FDG-PET were used to analyse the neural and metabolic activity of the brain. Both methods revealed a reduced activity in 3crit respect to 0crit. Interestingly, the modalities showed that the differences between 0crit and 3crit were located in the right or left hemisphere depending on the area, suggesting a lateralization of the brain.
Our multimodal neuroimaging data are in support for divergent brain adaptations between addicted-like and non-addicted-like rats and are informative to interpret differences in brain adaptations occurring in dependent and non-dependent cocaine users.