Effects of prenatal alcohol and delta-9-tetrahydrocannabinol exposure via electronic cigarettes on motor development

Abstract

Background: Prenatal alcohol exposure can lead to a wide range of neurological and behavioral deficits, including alterations in motor domains. However, much less is known about the effects of prenatal cannabis exposure on motor development, despite cannabis being the most consumed illicit drug among women. Cannabis use among pregnant women has become increasingly popular given the widespread perception that consumption is safe during pregnancy. Moreover, alcohol and cannabis are commonly used together, even among pregnant women. Yet few studies have explored the potential consequences of combined prenatal exposure on behavioral domains.

Methods: Using our previously established model, during gestational days 5 to 20, four groups of pregnant Sprague-Dawley rats were exposed to vaporized alcohol, delta-9-Tetrahydrocannabinol (THC) via electronic (e-) cigarettes, the combination of alcohol and THC, or a vehicle. Following birth, offspring were tested on early sensorimotor development, adolescent motor coordination, and adolescent activity levels.

Results: Prenatal THC e-cigarette exposure delayed sensorimotor development early in life and impaired motor coordination later in early adolescence; combined prenatal alcohol and THC exposure did not have additive effects on sensorimotor development. However, combined prenatal exposure produced hyperactivity among male offspring.

Conclusions: Prenatal cannabis exposure may lead to impaired motor skills throughout early development and combined exposure with alcohol during gestation may lead to hyperactivity in early adolescence. These findings have important implications for informing pregnant women of the risks to the fetus associated with prenatal cannabis exposure, with and without alcohol, and could influence public policy.

Keywords: THC; alcohol; e-cigarette; motor; prenatal.

FIGURE 1

Timeline of the study design

FIGURE 2

Offspring from Cohort 1 exposed to THC prenatally weighed significantly less throughout the early sensorimotor development paradigm (postnatal days 12 to 20; A) and the parallel bar paradigm (PD 30 to 32; B), alone or in combination with alcohol. Separately, there was an overall reduction in body weight of alcohol‐exposed subjects on PD 32 (B), an effect driven by the combined exposure group in Cohort 1. In Cohort 2, offspring exposed to THC alone weighed less than all other prenatal exposure groups during the open‐field activity testing (C). ** = THC (collapsed) < Vehicle (collapsed), p's < 0.05. * = EtOH (collapsed) < Air (collapsed), p = 0.05. *** = Air + THC < all other groups, p's < 0.05

FIGURE 3

Prenatal exposure to THC via e‐cigarettes delayed early sensorimotor development. Although subjects exposed to any prenatal THC showed developmental delays (A), their motor development eventually caught up with that of controls (B). ** = THC (collapsed) > Vehicle (collapsed), p < 0.05. * = EtOH + THC < EtOH + Vehicle and Air + Vehicle, p's < 0.05. *** = Air + THC < Air + Vehicle, p < 0.05

FIGURE 4

Prenatal THC exposure impaired motor coordination in adolescent subjects, increasing the number of trials before the first success (A), decreasing success ratios (B), and decreasing the maximum width achieved (C). ** = THC (collapsed) significantly different from Vehicle (collapsed) p's < 0.05. * = EtOH > EtOH + THC and Air + THC, p < 0.001

FIGURE 5

Among female offspring, prenatal EtOH or THC exposure separately increased activity levels during the middle of the sessions compared with controls (B). In contrast, combined exposure to prenatal EtOH and THC significantly increased activity levels among male offspring overall on Day 1 (C), as well as toward the end of the testing sessions (D). * = EtOH + Vehicle > Air + Vehicle, p's < 0.05. ** = Air + THC > Air + Vehicle, p < 0.05. ⁺ = Air + THC > Air + Vehicle, p = 0.06. *** = EtOH + THC > all other groups, p's < 0.05

FIGURE 6

Prenatal exposure did not significantly change the distance traveled in the center of the chamber among females on any day of activity testing (A) or across testing sessions (B). However, male offspring exposed to the combination of alcohol and THC prenatally traveled greater distances on Days 1 and 3 of testing (C) and throughout the testing session durations (D), indicating impaired habituation. *** = EtOH + THC > all other groups, p < 0.05

FIGURE 7

Prenatal exposure to alcohol and/or THC did not significantly alter the time spent in the center of the chamber among female offspring (A and B). However, combined exposure to alcohol and THC generally increased the center time of male offspring in the open field on Day 1 (C) and at the end of the testing sessions (D). *** = EtOH + THC > all other groups; p's < 0.05

FIGURE 8

Prenatal exposure did not significantly change the frequency of rearing in the open‐field chamber among either sex (A). All offspring exposed to alcohol prenatally reared less than those exposed to air at the beginning of the session (B). * = EtOH (collapsed) < Air (collapsed), p < 0.05