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The Journal of Neuroscience, February 2, 2005, 25(5):1132-1136; doi:10.1523/JNEUROSCI.3801-04.2005

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BRIEF COMMUNICATION
Estrogen Influences Cocaine-Induced Blood Oxygen Level-Dependent Signal Changes in Female Rats

Marcelo Febo,1 Craig F. Ferris,1 and Annabell C. Segarra2

1Center for Comparative NeuroImaging, Department of Psychiatry, University of Massachusetts Medical School, Worcester, Massachusetts 01655, and 2Department of Physiology and Biophysics, University of Puerto Rico Medical School, San Juan, Puerto Rico 00936

We investigated the effect of estrogen on cocaine-induced brain activity using blood oxygen level-dependent (BOLD) magnetic resonance imaging. Ovariectomized (Ovx) rats without estrogen and Ovx rats with estrogen (Ovx+E) were given a single saline or cocaine injection (15 mg/kg, i.p.) for 5 d. After 7 d of withdrawal from injections, rats were challenged with cocaine during functional imaging. Acute cocaine administration produced positive BOLD activation in the prefrontal cortex, nucleus accumbens, striatum, ventral tegmental area, and hippocampus, among other brain regions. Positive BOLD signal changes were lower in Ovx+E than in Ovx rats. With repeated cocaine administration, Ovx+E rats showed enhanced BOLD signal changes in the nucleus accumbens, ventral tegmental area, and hippocampus compared with acutely treated animals. Our results indicate that estrogen influences the effects of acute and repeated cocaine administration on BOLD signal changes. The data suggest that in females with estrogen, cocaine-induced neuronal activity is enhanced after repeated cocaine administration. It is possible that the actions of estrogen within the aforementioned brain regions potentiate the behavioral response to cocaine observed in female rats.

Key words: cocaine sensitization; female rats; estrogen; functional magnetic resonance imaging; BOLD signal; sex differences; VTA; cerebral blood flow; nucleus accumbens; hippocampus; hypercapnia; radiofrequency electronics

Received June 16, 2004; revised December 20, 2004; accepted December 20, 2004.






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