Oestradiol Alters Central 5- HT1 A Receptor Binding Potential Differences Related to Psychosocial Stress but not Differences Related to 5- HTTLPR Genotype in Female Rhesus Monkeys.

Autor: Michopoulos, V., Perez Diaz, M., Embree, M., Reding, K., Votaw, J. R., Mun, J., Voll, R. J., Goodman, M. M., Wilson, M., Sanchez, M., Toufexis, D.
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Zdroj: Journal of Neuroendocrinology; Feb2014, Vol. 26 Issue 2, p80-88, 9p
Abstrakt: Social subordination in female macaques represents a well-described model of chronic psychosocial stress. Additionally, a length polymorphism (5- HTTLPR) in the regulatory region of the serotonin (5- HT) transporter (5- HTT) gene ( SLC6A4) is present in rhesus macaques, which has been linked to adverse outcomes similar to that described in humans with an analogous 5- HTTLPR polymorphism. The present study determined the effects of social status and the 5- HTTLPR genotype on 5- HT1 A receptor binding potential (5- HT1 A BPND) in brain regions implicated in emotional regulation and stress reactivity in ovariectomised female monkeys, and then assessed how these effects were altered by 17β-oestradiol ( E2) treatment. Areas analysed included the prefrontal cortex [anterior cingulate ( ACC); medial prefrontal cortex (m PFC); dorsolateral prefrontal cortex; orbitofrontal prefrontal cortex], amygdala, hippocampus, hypothalamus and raphe nucleui. Positron emission tomography using p-[18 F] MPPF was performed to determine the levels of 5- HT1 A BPND under a non- E2 and a 3-week E2 treatment condition. The short variant (s-variant) 5- HTTLPR genotype produced a significant reduction in 5- HT1A BPND in the m PFC regardless of social status, and subordinate s-variant females showed a reduction in 5- HT1 A BPND within the ACC. Both these effects of 5- HTTLPR were unaffected by E2. Additionally, E2 reduced 5- HT1 A BPND in the dorsal raphe of all females irrespective of psychosocial stress or 5- HTTLPR genotype. Hippocampal 5- HT1 A BPND was attenuated in subordinate females regardless of 5- HTTLPR genotype during the non- E2 condition, an effect that was normalised with E2. Similarly, 5- HT1 A BPND in the hypothalamus was significantly lower in subordinate females regardless of 5- HTTLPR genotype, an effect reversed with E2. Taken together, the data indicate that the effect of E2 on modulation of central 5 HT1 A BPND may only occur in brain regions that show no 5- HTTLPR genotype-linked control of 5- HT1 A binding. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index
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