Nature Vs Nurture: Cocaine Exposed Spermatogonia Impact Behavior and Executive Functions of Naïve Offspring

Cocaine in the form of Coca Leaf has been in use for many centuries, particularly in the Andean culture of South America to counter the environmental effects of high altitude and other physiological disorders. In recent decades, much of Western society has now been plagued with abuse of refined cocaine however, where it has become a major public health problem currently impacting over 20 million adults and adolescent youth. In chronic use, cocaine contributes to dopaminergic euphoria and aberrant behaviour, and may contribute to epigenetic damage to gene expression in unsuspecting offspring. To determine the effects of chronic cocaine use by males on the offspring of naïve females, groups of 60-day old lean LA/Ntul//-cp rats were reared from weaning on standard Purina chow and house water, and administered 0 (Controls), 30 (Low Dose), or 60 (High Dose) mg/kg body weight of cocaine HCL daily for 90±2 days to fully encompass the duration of spermatogenesis. Opiate treated males were then mated with 82±3 day-old normally reared naive virgin females of the same strain that had never previously been exposed to the opioid or to a mating partner. Behavioral activity of each dosage level was assessed by subjecting the offspring postweaning at 21 days of age with a Stoelting activity wheel and a Calvin Hall open access exploratory field test. Offspring of pups were found to exhibit dose-related decreases in Stoelting wheel activity, with the greatest decrease at the highest dose administered (p=<0.01). Opiate treatment resulted in a latency in onset of exploratory activity at both dosage levels, and decreased exploratory activity in both inner squares and outer squares at the low dose group; In contrast, the High Dose group demonstrated an increase in outer square exploration and in the total numbers of squares explored compared to the Low Dose groups or Controls. These results suggest that male cocaine exposure during spermatogenesis may result in longstanding dose related behavioral changes in the offspring of naive females and may predispose them to potential opioid-linked behavioral changes upon weaning, adolescence and later stages of life.