Effect of Paternal Preconception Opiate Exposure on Exploratory Behavior and Thigmotaxis in Naive Offspring in Weanling Rats

Abstract

Opiate use in Industrialized communities has reached near epidemic proportions and impacts the lives and activities of many who succumb to its use and abuse. In its native form, leaves of the coca tree have been in use for many centuries, particularly in the mountainous areas of South America and Andean culture where it was used to accommodate to the altitude and other issues. Because purified cocaine extracts common to Western culture have been reported to bind to surface domains of spermatozoa, it could readily become incorporated into ova upon their sperm penetration and fertilization. Alternatively, chronic paternal cocaine use could theoretically impose as yet unknown DNA damage to haploid DNA strands prior to fertilization. Cocaine is associated with proven damage to DNA, where it has been linked to disrupted DNA strands that when replicated in the developing blastocyst may undergo further replication during subsequent cell divisions and impact learning and behaviour effects soon after birth and weaning in the affected rat pups. Virgin male rats were administered 60 mg cocaine/kg BW, s.c. for >90 days to encompass the duration of de novo spermatozoa maturation (est. 54 days) and mated with never exposed, naive virgin females of a similar age. Offspring were observed for spontaneous activity and exploratory activity in a Stoelting Wheel (SWA) and a Calvin Hall Open Maze (CHOM) at 21 days of age. SWA was decreased by 33% and CHOM indicated a 40% decreased latency for initial exploration associated with greater outer and total square exploration. These observations are indicative of decreased onset but heightened exploratory activity in the outer square exploration activity squares. In conclusion, pre-fertilization cocaine exposure of spermatozoa may contribute to impaired learning and dopaminergic mediated thigmotaxic behavioral attributes of unclear origin in offspring of naive females.