Transgenerational memory deficits in cocaine-sired male rat offspring and grand-offspring.

Environmental insults, including exposure to drugs of abuse, can influence offspring physiology and behavior through intergenerational epigenetic modifications. The present data indicated that paternal rat cocaine self-administration had no effect on stress responses, impulse control or cocaine seeking in male offspring. We also replicated previous findings showing that paternal cocaine intake impaired memory function, measured by the object location memory task, only in male offspring. We extended this work by breeding cocaine-exposed males with naïve females 90 days after the last cocaine self-administration session; that is, after one complete cycle of spermatogenesis. Impaired object recognition was observed in cocaine-sired male offspring with delayed mating, suggesting persistent cocaine-induced changes in sperm. We next wanted to discern if this hippocampal-dependent memory deficit would extend to the grand-offspring (i.e. the F2 generation). Our results indicated that male, but not female, cocaine grand-sired offspring displayed object location memory deficits, although the hippocampal mechanisms underlying this effect appear to differ between F1 and F2 generations. Taken together, our findings indicate that paternal cocaine exposure results in transgenerational hippocampal-dependent memory deficits.