5-HT_1A sex based differences in B_max, in vivo K_D, and BP_ND in the nonhuman primate

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• 作者：Dustin W. Wooten^a ; ^b ; ^{dwooten@wisc.edu} ; Ansel T. Hillmer^a ; ^b ; Jeffrey M. Moirano^a ; ^b ; Dana L. Tudorascu^c ; Elizabeth O. Ahlers^b ; Maxim S. Slesarev^b ; Todd E. Barnhart^a ; Jogeshwar Mukherjee^e ; Mary L. Schneider^b ; ^d ; Bradley T. Christian^a ; ^b ; ^f
• 关键词：5-HT ; Serotonin ; 5-HT1A ; Bmax ; KD ; Sex differences
• 刊名：NeuroImage
• 出版年：2013
• 出版时间：15 August, 2013
• 年：2013
• 卷：77
• 期：Complete
• 页码：125-132
• 全文大小：592 K

文摘

Serotonin (5-HT) dysfunction has been implicated in neuropsychiatric illnesses and may play a pivotal role in the differential prevalence of depression between the sexes. Previous PET studies have revealed sex-based differences in 5-HT_1A binding potential (BP_ND). The binding potential is a function of the radioligand-receptor affinity (1/K_Dapp), and receptor density (B_max). In this work, we use a multiple-injection (MI) PET protocol and the 5-HT_1A receptor antagonist, [¹⁸F]mefway, to compare sex-based differences of in vivo affinity, B_max, and BP_ND in rhesus monkeys.

Methods

PET [¹⁸F]mefway studies were performed on 17 (6 m, 11f) rhesus monkeys using a 3-injection protocol that included partial saturation injections of mefway. Compartmental modeling was performed using a model to account for non-tracer doses of mefway for the estimation of K_Dapp and B_max. BP_ND estimates were also acquired from the first injection (high specific activity [¹⁸F]mefway, 90-minute duration) for comparison using the cerebellum (CB) as a reference region. Regions of interest were selected in 5-HT_1A binding regions of the hippocampus (Hp), dorsal anterior cingulate cortex (dACC), amygdala (Am), and raphe nuclei (RN).

Results

Female subjects displayed significantly (*p < 0.05) lower K_Dapp in the Hp (? 32 % ), Am (? 38 % ), and RN (? 37 % ). Only the Hp displayed significant differences in B_max with females having a B_max of ? 29 % compared to males. Male subjects demonstrated significantly lower BP_ND measurements in the Am (14 % ) and RN (29 % ).

Conclusion

These results suggest that the higher BP_ND values found in females are the result of lower [¹⁸F]mefway K_Dapp. Although a more experimentally complex measurement, separate assay of K_Dapp and B_max provides a more sensitive measure than BP_ND to identify the underlying differences between females and males in 5-HT_1A function.