The effects of prenatal nicotine and THC E-cigarette exposure on motor development in rats

Abstract

In the United States, nicotine and cannabis are the most common licit and illicit drugs used among pregnant women. Importantly, nicotine and cannabis are now being combined for consumption via e-cigarettes, an increasingly popular route of administration. Both nicotine and tetrahydrocannabinol (THC), the primary psychoactive component of cannabis, cross the placenta barrier. However, the consequences of prenatal cannabis use are not well understood, and less is known about potential combination effects when consumed with nicotine, especially via e-cigarettes. The present study used a rodent model to examine how prenatal e-cigarette exposure to nicotine, THC, and the combination impacts motor development among offspring.Pregnant Sprague-Dawley rats were exposed to nicotine (36 mg/mL), THC (100 mg/mL), the combination, or vehicle via e-cigarette inhalation from gestational days (GD) 5-20. One sex pair per litter was tested on an early sensorimotor development task (postnatal days [PD] 12-20) and a parallel bar motor coordination task . Combined prenatal exposure to nicotine and THC delayed sensorimotor development, even though neither drug produced impairments on their own. In contrast, prenatal exposure to either nicotine or THC impaired motor coordination, whereas combined exposure exacerbated these effects, particularly among females. These data illustrate that prenatal exposure to either nicotine or THC may alter motor development, and that the combination may produce more severe effects. These findings have important implications for pregnant women as we better understand the teratogenic effects of these drugs consumed via e-cigarettes.

A Model of Combined Exposure to Nicotine and Tetrahydrocannabinol via Electronic Cigarettes in Pregnant Rats

“…While possible, this would not explain the consistency of body temperature changes caused by each drug, or the reduction of plasma level differences over time, with or without co-exposure. Moreover, we have found that the administrative parameters used in this study induce unique, additive, and interactive effects in the behavior of the offspring ( Hussain et al, 2021 ; Rodriguez et al, 2021 ); it would be difficult to explain how the combination could produce more severe behavioral alterations in the offspring if less drug was absorbed. It is also possible that the combination of nicotine and THC may speed up drug distribution from the blood into other body tissues.…”

“…Importantly, we did not observe any dams licking the sides of the cages or their own fur during the paradigm, nor did we see/feel any condensate on their fur upon removal or during the entirety of blood collection timelines. In sum, these data suggest that offspring outcome effects produced at these doses, such as behavioral alterations ( Hussain et al, 2021 ; Rodriguez et al, 2021 ), are not related to nutritional confounds, nor are pair-fed controls required ( Abel and Dintcheff, 1978 ).…”

Adult consequences of repeated nicotine vapor inhalation in adolescent rats

“…Given that inhalation of drugs can produce a similar subjective high at a lower plasma concentration even compared with intravenous delivery in humans (Cook et al, 1993), it is critical to determine whether inhalation produces lasting consequences. Recent work from Breit and colleagues has provided evidence that this is may be the case; prenatal exposure to nicotine via ENDS vapor was shown to impair adolescent motor coordination in rats (Hussain et al, 2022).…”

Emerging Roles of Endocannabinoids as Key Lipid Mediators for a Successful Pregnancy

“…These neurochemical alterations might contribute to the higher susceptibility to develop neurodevelopmental and psychiatric disorders in the children of mothers who used Cannabis during pregnancy [ 28 , 29 , 222 , 224 ]. This conclusion is supported by many studies performed in animal models, in which a wide spectrum of behavioral and neural alterations have been reported in the offspring of dams prenatally exposed to Cannabis [ 226 , 227 , 228 , 229 , 230 , 231 , 232 , 233 , 234 , 235 , 236 , 237 , 238 , 239 ]. Interestingly, Rompala and colleagues recently found that emotional dysregulations in children whose mothers were Cannabis users are associated with increased stress hormone levels in the hair and, intriguingly, reduced immune-related gene expression in the placenta, suggesting that the atypical behavioral traits induced by prenatal Cannabis exposure might be partly linked to the immunosuppressive effects of cannabinoids [ 240 ].…”