The neural consequences of repeated cocaine exposure revealed by functional MRI in awake rats.
The use of functional magnetic resonance imaging (fMRI) in animal models of cocaine addiction is an invaluable tool for investigating the neuroadaptations that lead to this psychiatric disorder. We used blood-oxygen-level-dependent (BOLD) MRI in awake rats to identify the neuronal circuits affected by repeated cocaine administration. Rats were given an injection of cocaine (15 mg/kg, i.p.) or its vehicle for 7 days, abstained from injections for 1 week, and challenged with an intracerebroventricular cocaine injection during functional imaging. Acute cocaine produced robust positive BOLD responses across well-known monoamine-enriched brain regions, such as the prefrontal cortex, nucleus accumbens, dorsal striatum, sensory cortex, hippocampus, thalamus, and midbrain areas. However, repeated cocaine administration resulted in lower BOLD responses in the prefrontal cortex, agranular insular cortex, nucleus accumbens, ventral pallidum, and dorsomedial thalamus, among other brain regions. Reductions in BOLD intensity were not associated with variations in cerebrovascular reactivity between drug naive rats and those repeatedly exposed to cocaine. Therefore, the lower metabolic activation in response to cocaine could reflect a reduced neuronal and/or synaptic activity upon repeated administration.
Febo
Marcelo
M
Psychiatry Department, Center for Comparative NeuroImaging, University of Massachusetts Medical School, Worcester, MA 01604, USA. Marcelo.Febo@umassmed.edu
Segarra
Annabell C
AC
Nair
Govind
G
Schmidt
Karl
K
Duong
Timothy Q
TQ
Ferris
Craig F
CF
D000818:Animals; D015306:Biogenic Monoamines / Q000378:metabolism; D001921:Brain / Q000187:drug effects*; D001923:Brain Chemistry / Q000187:drug effects*; D002245:Carbon Dioxide / Q000494:pharmacology; D003042:Cocaine / Q000008:administration & dosage / Q000494:pharmacology*; D006454:Hemoglobins / Q000378:metabolism; D007276:Injections, Intraventricular; D008279:Magnetic Resonance Imaging; D008297:Male; D010100:Oxygen / Q000097:blood; D010101:Oxygen Consumption / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley
D015306:Biogenic Monoamines; D006454:Hemoglobins; D002245:Carbon Dioxide; C100003:deoxyhemoglobin; D003042:Cocaine; D010100:Oxygen