The effects of early postnatal stimulation on Morris water-maze acquisition in adult mice: genetic and maternal factors

Abstract

Following stressor exposure BALB/cByJ mice exhibit hypersecretion of corticosterone and marked brain catecholamine alterations. In addition, mice of this strain exhibit impairments of performance in a Morris water-maze, which may be exacerbated by footshock application. In the present investigation it was demonstrated that early-life handling of mouse pups (coupled with brief separation periods from the dam over the course of 21 days postpartum) reduced the learning impairments seen when mice were tested in the Morris water-maze at 120 days of age and also prevented stress-induced disturbances in this task. Likewise, cross-fostering BALB/cByJ mice with a C57BL/6ByJ dam prevented the performance deficits. In contrast, C57BL/6ByJ mice cross-fostered to a BALB/cByJ dam exhibited proficient performance. Thus, maternal factors may be important in determining the Morris water-maze disturbances, provided that this was applied on the BALB/cByJ genetic background. Stressor exposure exacerbated the performance disturbances in BALB/cByJ mice, while diazepam treatment disrupted Morris water-maze performance in both BALB/cByJ and C57BL/6ByJ mice. Paralleling the behavioral changes associated with handling, the stress-induced hypercorticosterone secretion characteristic of the BALB/cByJ mouse was attenuated by the early handling procedure. Stressor exposure also produced strain-dependent variations of NE and 5-HT, but these effects were not appreciably influenced by the handling procedure. These data are consistent with the proposition that performance disturbances of BALB/cByJ mice tested in the Morris water-maze task are associated with excessive hypothalamic-pituitary-adrenal reactivity. Moreover, it appears that the influence of early-life stimulation may interact with genetic factors in determining endocrine and behavioral stress responses.

Mice Deficient for Both Corticotropin-Releasing Factor Receptor 1 (CRFR1) and CRFR2 Have an Impaired Stress Response and Display Sexually Dichotomous Anxiety-Like Behavior

“…These results suggest then that the reason CRFR1-mutant male mice previously reported to display dramatic anxiolytic-like behaviors are now not statistically different from controls is attributable to an effect of their mother's genotype. Previous studies have well defined the nurturing roll of the dam and how this behavior may affect the adult anxiety of the pup, suggesting that a low-nurturing mother leads to a highanxiety pup (Zaharia et al, 1996;Caldji et al, 1998). In addition, studies have also shown that the stress hormone levels of the dam during pregnancy affect the anxiety levels of the pups (Takahashi et al, 1988(Takahashi et al, , 1990(Takahashi et al, , 1992Takahashi and Kalin, 1991;Cratty et al, 1995;Vallee et al, 1997).…”

Rearing Effects on Cerebrospinal Fluid Oxytocin Concentration and Social Buffering in Rhesus Monkeys

“…Indeed, several recent studies in rats have described the long-term neural as well as behavioral consequences of variations in early social experience. Reduced maternal grooming and licking is associated with significant and persistent differences in the adult offspring's emotionality (Caldji et al, 1998), cognition (Zaharia et al, 1996), hypothalamic CRH, and AVP mRNA expression (Liu et al, 1997), as well as binding to GABA A , CRH, a 2 -adrenergic (Caldji et al, 1998), and glucocorticoid receptors in the brain (Sutanto et al, 1996). Two independent groups have reported a decrease in OT receptor binding in the amygdala, following repeated mother-infant separations or decreased maternal licking and grooming (Francis et al, 2000;Noonan et al, 1994).…”

Epigenetic Mechanisms in Learned Fear: Implications for PTSD

“…This work has received attention among PTSD researchers because of the parallel findings in humans, which link hypothalamic-pituitary-adrenal axis dysregulation and childhood maltreatment with predisposition to PTSD (Binder et al, 2008;Shea et al, 2005;Yehuda and LeDoux, 2007). Specifically, Meaney's lab has shown that natural variations in maternal licking and grooming alter DNA methylation and the expression of the glucocorticoid receptor gene, and produce altered patterns of hypothalamic-pituitary-adrenal axis reactivity, anxiety, and cognitive function in adulthood (Francis and Meaney, 1999;Liu et al, 2000;Meaney and Szyf, 2005a;Weaver et al, 2002a;Weaver et al, 2002b;Zaharia et al, 1996). These studies implicate epigenetic mechanisms in providing a critical link between early-life environment and sensitivity to stressors in later life, which is critical for developing a complete model of PTSD that integrates pre-existing risk factors with an exaggerated response to trauma in adulthood.…”