title: Neuroimaging evidence of altered fronto-cortical and striatal function after prolonged cocaine self-administration in the rat.
abstract: Cocaine addiction is often modeled in experimental paradigms where rodents learn to self-administer (SA) the drug. However, the extent to which these models replicate the functional alterations observed in clinical neuroimaging studies of cocaine addiction remains unknown. We used magnetic resonance imaging (MRI) to assess basal and evoked brain function in rats subjected to a prolonged, extended-access cocaine SA scheme. Specifically, we measured basal cerebral blood volume (bCBV), an established correlate of basal metabolism, and assessed the reactivity of the dopaminergic system by mapping the pharmacological MRI (phMRI) response evoked by the dopamine-releaser amphetamine. Cocaine-exposed subjects exhibited reduced bCBV in fronto-cortical areas, nucleus accumbens, ventral hippocampus, and thalamus. The cocaine group also showed an attenuated functional response to amphetamine in ventrostriatal areas, an effect that was significantly correlated with total cocaine intake. An inverse relationship between bCBV in the reticular thalamus and the frontal response elicited by amphetamine was found in control subjects but not in the cocaine group, suggesting that the inhibitory interplay within this attentional circuit may be compromised by the drug. Importantly, histopathological analysis did not reveal significant alterations of the microvascular bed in the brain of cocaine-exposed subjects, suggesting that the imaging findings cannot be merely ascribed to cocaine-induced vascular damage. These results document that chronic, extended-access cocaine SA in the rat produces focal fronto-cortical and striatal alterations that serve as plausible neurobiological substrate for the behavioral expression of compulsive drug intake in laboratory animals.
authors.affiliation: Center for Nanotechnology Innovation, Istituto Italiano di Tecnologia @NEST, Pisa, Italy. alessandro.gozzi@iit.it
authors.forename: Alessandro
authors.initials: A
authors.lastname: Gozzi
authors.forename: Michela
authors.initials: M
authors.lastname: Tessari
authors.forename: Lisa
authors.initials: L
authors.lastname: Dacome
authors.forename: Federica
authors.initials: F
authors.lastname: Agosta
authors.forename: Stefano
authors.initials: S
authors.lastname: Lepore
authors.forename: Anna
authors.initials: A
authors.lastname: Lanzoni
authors.forename: Patrizia
authors.initials: P
authors.lastname: Cristofori
authors.forename: Emilio M
authors.initials: EM
authors.lastname: Pich
authors.forename: Mauro
authors.initials: M
authors.lastname: Corsi
authors.forename: Angelo
authors.initials: A
authors.lastname: Bifone
mesh_terms: D000818:Animals; D003042:Cocaine / Q000008:administration & dosage*; D019970:Cocaine-Related Disorders / Q000503:physiopathology*; D003342:Corpus Striatum / Q000187:drug effects / Q000502:physiology*; D005625:Frontal Lobe / Q000187:drug effects / Q000502:physiology*; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D009434:Neural Pathways / Q000187:drug effects / Q000502:physiology; D059906:Neuroimaging / Q000379:methods; D051381:Rats; D012646:Self Administration; D013997:Time Factors
chemical_list: D003042:Cocaine