TY - JOUR
T1 - The neural consequences of repeated cocaine exposure revealed by functional MRI in awake rats
AU - Febo, Marcelo
AU - Segarra, Annabell C.
AU - Nair, Govind
AU - Schmidt, Karl
AU - Duong, Timothy Q.
AU - Ferris, Craig F.
N1 - Funding Information:
This work was partially funded by a National Institute of Health NIDA Grant (R01 DA13517) to Craig F Ferris and an NINDS Grant (Specialized Neuroscience Research Program U54 NS39405) to Annabell C Segarra. An NIDA Minority Supplement Award provided support for Marcelo Febo. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIDA and NINDS.
PY - 2005/5
Y1 - 2005/5
N2 - 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 (15mg/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 naïve 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.
AB - 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 (15mg/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 naïve 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.
KW - Awake rat
KW - BOLD imaging
KW - Cocaine
KW - Drugs of abuse
KW - Functional MRI
KW - Reward circuitry
KW - Sensitization
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U2 - 10.1038/sj.npp.1300653
DO - 10.1038/sj.npp.1300653
M3 - Article
C2 - 15637636
AN - SCOPUS:17644376834
SN - 0893-133X
VL - 30
SP - 936
EP - 943
JO - Neuropsychopharmacology
JF - Neuropsychopharmacology
IS - 5
ER -