Ison JR, Allen PD. Pre- but not post-menopausal female CBA/CaJ mice show less prepulse inhibition than male mice of the same age. Behav Brain Res 185: 76-81

Department of Brain & Cognitive Sciences, University of Rochester, Rochester, NY 14627, USA.
Behavioural Brain Research (Impact Factor: 3.03). 01/2008; 185(2):76-81. DOI: 10.1016/j.bbr.2007.07.014
Source: PubMed


Prepulse inhibition (PPI) of the acoustic startle reflex (ASR) has been reported to be weaker in females than males for both humans and rats. Although there are exceptions, on balance these data suggest that PPI is sensitive to sex-specific neurosteroids; in contrast, most studies with mice have not replicated this effect. We compared PPI for noise decrement prepulses (quiet gaps) in female CBA/CaJ mice at 3-8 months (pre-menopausal: n = 55) and 17-25 months of age (post-menopausal, n = 33) with similarly aged groups of males (n = 48, 35). Both PPI and ASR levels were significantly reduced in pre-menopausal females compared to young males, but did not differ between post-menopausal females and old males. The observed PPI decrement in young female mice compared to young males agrees with one previous report in young C57BL/6J mice as well as the majority of studies with human subjects and some strains of rats. The absence of a sex difference in PPI for old mice is consistent with the hypothesis that PPI is affected by reproductive hormones present at high levels only in pre-menopausal females. We note that this effect size for PPI is small, perhaps consistent with reports that the PPI decrement in females is restricted to certain times within the menstrual cycle in women and the estrous cycle in rats. The negative findings previously reported in the mouse can be attributed to the small effect size and to procedural differences, including stimulus conditions, and the different strains and ages of mice.

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Available from: Paul D Allen, Dec 17, 2013
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    • "Thus decreased GluN2B subunit phosphorylation and possibly its activity in the hippocampus of young mice may be an attempt to prevent excitotoxicity, whereas increased GluN2B subunit phosphorylation in older mice may exacerbate excitotoxic events. Indeed, we demonstrate increased phosphorylated GluN2B subunits in the hippocampus of 15 month-old 3xTg-AD females, largely suggesting increased activity of GluN2B-containing NMDARs in postmenopausal animals, as female mice are considered to initiate menopause at 12–14 months of age (Ison and Allen, 2007). Gender differences in AD patients have been reported and the incidence of the disease appears to be higher in post-menopausal women than in age-matched men (Fratiglioni et al., 1997; Bonomo et al., 2009). "
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    • "Within each test, for a given mouse, startle amplitudes were averaged across all trials of the same stimulus conditions. PPI was defined as fractional reduction of startle, i.e., 1 minus the ratio of startle amplitude with vs. without prepulse (see, e.g., Ison and Allen 2007). Thus a value of 0 means no effect of the prepulse, a value of 1 means complete inhibition of startle, and a negative value indicates prepulse facilitation of the startle response. "
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    • "Furthermore, PPI varies in women according to the stage of the menstrual cycle, suggesting that variations in sex hormones can influence PPI (Swerdlow et al., 1997; Jovanovic et al., 2004). Sex differences in PPI have also been reported in Wistar rats and in mice (males > females; Lehmann et al., 1999; Ralph et al., 2001; Ison and Allen, 2007), and PPI varies across the estrus cycle in rats (Koch, 1998). Administration of estrogens and androgens can facilitate PPI (van den Buuse and Eikelis, 2001; Gogos and Van den Buuse, 2003), although little is known about the role of specific hormone receptors, including the AR, that may mediate these changes. "
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