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Psychoneuroendocrinology. 2014 Sep;47:88-97. doi: 10.1016/j.psyneuen.2014.05.005. Epub 2014 May 14.

Alterations in dopamine system function across the estrous cycle of the MAM rodent model of schizophrenia.

Author information

1
Department of Pharmacology & Center for Biomedical Neuroscience, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
2
Department of Pharmacology & Center for Biomedical Neuroscience, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA; Departments of Physiology and Pathophysiology, Medical School of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
3
Department of Pharmacology & Center for Biomedical Neuroscience, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA. Electronic address: LodgeD@uthscsa.edu.

Abstract

Clinical studies have reported differences in the incidence and severity of schizophrenia symptoms between male and female schizophrenia patients. Unfortunately, the cause of these differences is not currently known due, in part, to the fact that preclinical studies largely focus on male subjects. Dopamine neuron activity has been previously demonstrated to change across the estrous cycle, and may therefore be of relevance, as aberrant dopamine signaling is thought to underlie the positive symptoms of schizophrenia. Here we examine dopamine neuron activity across the estrous cycle in the MAM rodent model of schizophrenia. We demonstrate that the elevation in dopamine neuron activity, consistently observed in male MAM-treated rats, is most prominent during estrus and attenuated in met-estrus. Furthermore, this appears to be mediated, in part, by progesterone in the ventral hippocampus, as increases in dopamine neuron population activity (observed in estrus) were normalized by the intra-hippocampal administration of the progesterone receptor antagonist, mifepristone (but not the estrogen receptor antagonists, fulvestrant). Taken together, these data suggest that changes in dopamine system function occur across the estrous cycle in MAM-treated rats and may contribute to the differences in symptomatology between male and female schizophrenia patients.

KEYWORDS:

Dopamine; Estrous cycle; Hippocampus; Progesterone; Schizophrenia

PMID:
25001958
PMCID:
PMC4106681
DOI:
10.1016/j.psyneuen.2014.05.005
[Indexed for MEDLINE]
Free PMC Article
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