Attenuation by a sigma1 (σ1) receptor agonist of the learning and memory deficits induced by a prenatal restraint stress in juvenile rats

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Abstract
Stress during pregnancy results in complex neurochemical and behavioral alterations throughout the offspring lifetime. We here examined the impact of prenatal stress (PS) on memory functions in male and female offspring and report the efficacy of a selective sigma1 (σ1) receptor agonist, igmesine, in alleviating the observed deficits. Dams received an unpredictable 90‐min duration restraint stress from gestational day E17 to E20. Learning was examined in offspring between day P24 and P36 using spontaneous alternation in the Y‐maze, delayed alternation in the T‐maze, water‐maze learning and passive avoidance. Both male and female PS rats showed impairments of spontaneous and delayed alternation performances. Acquisition of a fixed platform position in the water‐maze was unchanged in PS rats, but the probe test revealed a diminution of time spent in the training quadrant. Acquisition of a daily changing platform position demonstrated impaired working memory for male and female PS rats. Finally, passive avoidance deficits were observed. Pretreatment with the selective σ1 agonist igmesine (1–10 mg kg−1 i.p.) reversed the PS‐induced learning deficits in offspring rats for each test. The σ1 antagonist BD1063 failed to affect performances alone but blocked the igmesine effect, confirming the involvement of the σ1 receptor. PS thus induces delayed memory deficits, affecting spatial and nonspatial, short‐ and long‐term memories in juvenile male and female offspring rats. Activation of the σ1 neuromodulatory receptor allows a significant recovery of the memory functions in PS rats. British Journal of Pharmacology (2004) 142, 689–700. doi:10.1038/sj.bjp.0705835

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