Integration of neural networks activated by amphetamine in females with different estrogen levels: A functional imaging study in awake rats. (June 2015)

• Record Type: Journal Article
• Authors: Madularu, Dan; Yee, Jason R.; Kenkel, William M.; Moore, Kelsey A.; Kulkarni, Praveen; Shams, Waqqas M.; Ferris, Craig F.; Brake, Wayne G.
• Is Part Of: Psychoneuroendocrinology. Volume 56(2015:Jun.)
• Page Start: 200
• Page End: 212
• Publication Date: 2015-06
• Subjects: Estradiol -- BOLD -- Schizophrenia -- Ovariectomy -- fMRI -- Amphetamine sensitization; Psychoneuroendocrinology -- Periodicals; Endocrinology -- Periodicals; Neurology -- Periodicals; Psychiatry -- Periodicals; Neuropsychoendocrinologie -- Périodiques; 616.8
• DOI: 10.1016/j.psyneuen.2015.02.022
• Languages: English
• ISSNs: 0306-4530

Abstract

Graphical abstract: Highlights: Amphetamine-sensitized, ovariectomized rats receiving estradiol were subjected to fMRI in response to peripheral amphetamine. Hormone level-dependent responses to amphetamine were observed. Effects of different levels of hormone involved structures associated with schizophrenia. Summary: 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, in rats, dopamine neurotransmission, which is a common target of all antipsychotic medications, 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, chronic low, or phasic 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 amphetamine-related BOLD activity is influenced by estrogen levels in sensitized female rats.