Integration of neural networks activated by amphetamine in females with different estrogen levels: A functional imaging study in awake rats.
Dan Madularu 1 , Jason R. Yee 2 , William M. Kenkel 2 , Kelsey A. Moore 2 , Praveen Kulkarni 2 , Waqqas M. Shams 1 , Craig F. Ferris 2 , and Wayne G. Brake 1
Concordia University, Montreal, QC, Canada,
University, Boston, MA, United States
Previous studies demonstrate that schizophrenia
symptomatology in women is dependent upon estrogen
levels. Estrogen has beneficial properties when
administered in conjunction with antipsychotics, and
estrogen also alters dopamine neurotransmission in rats;
suggesting a possible interaction between the two. The
aim of the current study was to investigate this
possible interaction using functional magnetic resonance
imaging in awake, female rats. Amphetamine-sensitized,
ovariectomized rats receiving no, low, or high levels of
estradiol replacement were used, and changes in
blood-oxygen-level-dependent (BOLD) signal were recorded
over time in response to an acute amphetamine injection.
Increasing levels of estradiol enhanced BOLD activation
in pathways previously known to be implicated in
schizophrenia symptomatology, such as the
mesocorticolimbic, habenular and olfactory pathways as
well as more widespread areas. We propose here the first
comprehensive amphetamine activation map integrating
brain regions where dopaminergic transmission is
influenced by estrogen levels.
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