Paternal cannabis extract exposure in rats: Preconception timing effects on neurodevelopmental behavior in offspring

Abstract

Maternal toxicant exposure during gestation can have deleterious effects on neurobehavioral development of the offspring. The potential risks engendered by paternal toxicant exposure prior to conception have been largely understudied. Recently, we found that chronic THC exposure prior to conception in male rats causes long-lasting behavioral impairment in their offspring. The current study examined the effects of chronic preconception exposure to cannabis smoke extract in Sprague-Dawley rats at two different phases in sperm development. One group received daily subcutaneous (sc) injections of THC in cannabis extract at 4 mg/kg/day for 28 days until three days prior to mating with untreated females (late exposure group). Another group received the same regimen except they underwent 56 days of drug abstinence prior to mating (early exposure group). These were compared with a control group treated with vehicle. The offspring underwent a battery of tests for behavioral function to assess motor, emotional and cognitive function. On the elevated plus maze test, the offspring of both paternal cannabis smoke extract (CSE) exposure groups had significantly more time on the open arms than control offspring, indicative of greater risk-taking behavior. No significant main effects of CSE exposure were seen on adolescent or adult locomotor activity in the figure-8 apparatus. In the novel object recognition test, there was a significantly greater drop-off in novel object preference across the session in the male, but not female offspring of the late exposure group. There was also a sex-selective effect of paternal CSE treatment in the 16-arm radial maze test of memory function. Female offspring of the late exposure group had significantly more working memory errors than control females in the first half of the 12-session training sequence. No significant effects were seen in the operant visual signal sustained detection test of attention. This study shows that there are long-lasting behavioral consequences of preconception CSE exposure through the paternal lineage in rats.

Keywords: Behavior; Cannabis; Intergenerational; Offspring; Paternal; Rat.