Beneficial effects of the sigma 1 receptor agonists igmesine and dehydroepiandrosterone against learning impairments in rats prenatally exposed to cocaine

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In utero cocaine (IUC) exposure results in offspring rats in complex neurochemical and behavioral alterations, particularly affecting learning and memory processes. We examined here the impact of IUC exposure on memory functions in male and female offspring rats and report that selective sigma 1 (σ 1) receptor agonists are effective in reversing the deficits. Dams received a daily cocaine, 20 mg/kg ip, injection between gestational days E17 to E20. Learning was examined in offspring between day P30 and P41 using delayed alternation in the T-maze, water-maze learning and passive avoidance. Both male and female rats prenatally exposed to cocaine showed delayed alternation deficits and impairments of acquisition of a fixed platform position in the water maze, as shown by higher acquisition latencies and diminutions of time spent in the training quadrant during the probe test. The acquisition of a daily changing platform position also demonstrated impaired working memory. Finally, passive avoidance deficits were observed. Pretreatment with the synthetic σ 1 agonist igmesine (0.1–1 mg/kg ip) or the neuroactive steroid dehydroepiandrosterone (DHEA 10–40 mg/kg ip) reversed the prenatal cocaine-induced learning deficits in offspring rats for each test. The σ 1 antagonist BD1063 (1 mg/kg ip) failed to affect performances alone but blocked the igmesine and DHEA effects, confirming the involvement of the σ 1 receptor. IUC exposure thus results in marked memory deficits, affecting spatial and nonspatial short- and long-term memories in juvenile male and female offspring rats. The activation of the σ 1 neuromodulatory receptor allows a complete behavioral recovery of the memory functions in prenatally cocaine-exposed rats.