title: Roles of testosterone and amygdaloid LTP induction in determining sex differences in fear memory magnitude.
abstract: Women are thought to form fear memory more robust than men do and testosterone is suspected to play a role in determining such a sex difference. Mouse cued fear freezing was used to study the sex-related susceptibility and the role of testosterone in fear memory in humans. A 75-dB tone was found to provoke weak freezing, while 0.15-mA and 0.20-mA footshock caused strong freezing responses. No sex differences were noticed in the tone- or footshock-induced (naïve fear) freezing. Following the conditionings, female mice exhibited greater tone (cued fear)-induced freezing than did male mice. Nonetheless, female mice demonstrated indistinctive cued fear freezing across the estrous phases and ovariectomy did not affect such freezing in female mice. Orchidectomy enhanced the cued fear freezing in male mice. Systemic testosterone administrations and an intra-lateral nucleus of amygdala (LA) testosterone infusion diminished the cued fear freezing in orchidectomized male mice, while pretreatment with flutamide (Flu) eradicated these effects. Long-term potentiation (LTP) magnitude in LA has been known to correlate with the strength of the cued fear conditioning. We found that LA LTP magnitude was indeed greater in female than male mice. Orchidectomy enhanced LTP magnitude in males' LA, while ovariectomy decreased LTP magnitude in females' LA. Testosterone decreased LTP magnitude in orchidectomized males' LA and estradiol enhanced LTP magnitude in ovariectomized females' LA. Finally, male mice had lower LA GluR1 expression than female mice and orchidectomy enhanced the GluR1 expression in male mice. These findings, taken together, suggest that testosterone plays a critical role in rendering the sex differences in the cued fear freezing and LA LTP. Testosterone is negatively associated with LA LTP and the cued fear memory in male mice. However, ovarian hormones and LA LTP are loosely associated with the cued fear memory in female mice.
authors: Institute of Basic Medical Sciences, National Cheng Kung University College of Medicine, Tainan 70101, Taiwan, ROC.
authors: Li-Shen
authors: LS
authors: Chen
authors: Institute of Basic Medical Sciences, National Cheng Kung University College of Medicine, Tainan 70101, Taiwan, ROC.
authors: Wen-Yu
authors: WY
authors: Tzeng
authors: Institute of Basic Medical Sciences, National Cheng Kung University College of Medicine, Tainan 70101, Taiwan, ROC.
authors: Jia-Ying
authors: JY
authors: Chuang
authors: Department of Health Psychology, Chang Jung Christian University, Tainan 71101, Taiwan, ROC.
authors: Chianfang G
authors: CG
authors: Cherng
authors: Department of Pharmacology, National Cheng Kung University College of Medicine, Tainan 70101, Taiwan, ROC.
authors: Po-Wu
authors: PW
authors: Gean
authors: Institute of Basic Medical Sciences, National Cheng Kung University College of Medicine, Tainan 70101, Taiwan, ROC; Institute of Behavioral Medicine, National Cheng Kung University College of Medicine, Tainan 70101, Taiwan, ROC. Electronic address: lungyu@mail.ncku.edu.tw.
authors: Lung
authors: L
authors: Yu
mesh_terms: D000679:Amygdala / Q000502:physiology*; D000818:Animals; D003213:Conditioning, Psychological / Q000187:drug effects; D003463:Cues; D005239:Fear / Q000187:drug effects / Q000502:physiology / Q000523:psychology*; D005260:Female; D046352:Freezing Reaction, Cataleptic / Q000187:drug effects; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008568:Memory / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D012727:Sex Characteristics; D013739:Testosterone / Q000494:pharmacology / Q000502:physiology*
chemical_list: D013739:Testosterone
keywords: Estrous cycle; Fear memory; Mice; Mood disorder; Sex difference; Testosterone