Beneficial effect of chronic nimodipine treatment on behavioral dysfunctions of aged rats exposed to perinatal ethanol treatment

Abstract

The long-term effects of prenatal and early postnatal ethanol exposure were assessed in adult (5-month), aged (24-month), and senescent (30-month) rats on non-aggressive intermale social behavior, and on black-white discrimination and spatial learning behaviors. Furthermore, the effects of chronic application of the Ca(2+) channel blocker nimodipine, which reportedly improves behavioral function in aging, were studied on the ethanol-induced behavioral deficits during aging. The results showed that the perinatal alcohol treatment suppressed social behavior by reducing the frequency and duration of social interactions at all ages. Black-white discrimination behavior and appetitively motivated learning in a hole-board were also markedly disturbed. Several measures of social and spatial learning behaviors of ethanol-exposed rats revealed progressive functional decline with aging. Chronic oral treatment with nimodipine improved the social activity and normalized the cognitive behavioral capabilities of aged and senescent rats exposed to ethanol. We concluded that: (1) the behavioral disabilities caused by perinatal ethanol toxicity are persistent in the rat lifespan and become more pronounced with aging; and (2) administration of nimodipine in the aging period improves, with a long-lasting efficacy, the ethanol-induced behavioral dysfunctions in aged rats.

A working model for the assessment of disruptions in social behavior among aged rats: The role of sex differences, social recognition, and sensorimotor processes

“…Overall, the findings reported here are consistent with the literature in which social behavior has been studied in aged rats (Andersen et al, 1999; Hunt et al, 2011; Markel et al, 1995; Salchner et al, 2004; Shoji and Mizoguchi, 2011; Soffié and Bronchart, 1988), thereby replicating a substantial decline in overall social behavior during senescence (Exps. 1 and 2) and extending those findings to female Fischer 344 rats (Exp.…”

“…Studies have demonstrated that aged rodents exhibit alterations in a number of behavioral domains, including impaired cognitive function (Barrientos et al, 2012; Foster, 2012; Gallagher and Rapp, 1997; Nomura and Okuma, 1999; Rosenzweig and Barnes, 2003), increased anxietylike (Boguszewski and Zagrodzka, 2002; Darwish et al, 2001; Frussa-Filho et al, 1991; Hunt et al, 2011; Imhof et al, 1993; Miyagawa et al, 1998) and depressive-like behaviors (Kiss et al, 2012; Moretti et al, 2011), decreased locomotor activity (Gage et al, 1984; Godbout et al, 2008; Hunt et al, 2011), and importantly, impaired social interaction (Andersen et al, 1999; Hunt et al, 2011; Markel et al, 1995; Mencio-Wszalek et al, 1992; Salchner et al, 2004; Shoji and Mizoguchi, 2011; Soffié and Bronchart, 1988). Aged male rats (14–30-months-old) have been reported to exhibit reduced play behavior (Soffié and Bronchart, 1988), fewer social interactions (Markel et al, 1995; Salchner et al, 2004), less social investigation (Andersen et al, 1999), and to engage in less contact with conspecifics (Hunt et al, 2011) relative to adolescent or young adult rats (1.5–6-months-old).…”

“…Aged male rats (14–30-months-old) have been reported to exhibit reduced play behavior (Soffié and Bronchart, 1988), fewer social interactions (Markel et al, 1995; Salchner et al, 2004), less social investigation (Andersen et al, 1999), and to engage in less contact with conspecifics (Hunt et al, 2011) relative to adolescent or young adult rats (1.5–6-months-old). Importantly, these aging-related social deficits are ubiquitous across many rat strains, including the Wistar (Andersen et al, 1999; Hunt et al, 2011; Markel et al, 1995; Soffié and Bronchart, 1988), Sprague-Dawley (Salchner et al, 2004), and Fischer 344/Brown Norway cross strains rats (Shoji and Mizoguchi, 2011), yet to our knowledge, only one study has examined potential sex differences in social behavior in aged animals. Hunt et al (2011) found that aged male and female Wistar rats (22–30 months) exhibited similar reductions in interaction with a novel age- and sex- matched social partner.…”

Dopamine and Aging: Intersecting Facets

“…-binding proteins calbindin-D 28K and calreticulin in cerebral cortex [120]. Nimodipine improved motor performance on balance, hanging and climbing tests and age-related alterations in limb coordination were delayed [128]. Nimodipine also enhances cerebral blood flow and T-and L-type Ca 2?…”

“…channel blockers (e.g., the L-type Ca 2? channel antagonist, nimodipine) enhance associative and spatial learning in old animals [120,[127][128][129].…”