Effects of Prenatal Nicotine, THC, or Co-Exposure on Cognitive Behaviors in Adolescent Male and Female Rats

Abstract

Introduction Although there has been a decrease in the prevalence of tobacco smoking, exposure to nicotine during pregnancy remains a substantial problem worldwide. Further, given the recent escalation in e-cigarette use and legalization of cannabis, it has become essential to understand the effects of nicotine and cannabinoid co-exposure during early developmental stages. Methods We systematically examined the effects of nicotine and/or THC prenatal exposure on cognitive behaviors in male and female offspring. Dams were exposed to nicotine vape or vehicle, and oral edible THC or vehicle, throughout pregnancy. Adolescent offspring were then tested in the prepulse inhibition test, novel object recognition task, and novelty suppressed feeding task. Results At birth, pups from mothers exposed to nicotine vape or oral THC exhibited reduced body weight, compared to control pups. Prenatal nicotine vape exposure resulted in a decreased baseline startle reactivity in adolescent male and female rats, and in females, enhanced sensorimotor gating in the prepulse inhibition test. Prenatal nicotine and THC co-exposure resulted in significant deficits in the prepulse inhibition test in males. Deficits in short-term memory were also found in males prenatally exposed to THC, either alone or with nicotine co-exposure, and in females exposed to THC alone. Finally, in males, a modest increase in anxiety-associated behaviors was found with THC or nicotine exposure in the latency to approach a novel palatable food. Conclusions These studies demonstrate differential effects of prenatal exposure to e-cigarette nicotine vape and/or edible THC on cognitive function, with differing effects within male and female groups. Implications These studies demonstrate an impact of nicotine, THC, or co-exposure during early developmental stages in utero on behavioral outcomes in adolescence. These findings have important translational implications given the continued use of nicotine and THC containing products by pregnant women worldwide, which can be applied to support healthcare and policy efforts restricting nicotine and THC use during pregnancy.

Prenatal Exposure to Δ9-Tetrahydrocannabinol Affects Hippocampus-Related Cognitive Functions in the Adolescent Rat Offspring: Focus on Specific Markers of Neuroplasticity

“…Our results indicate that prenatally THC-exposed rats display an impairment in memory formation when they are requested to remember the unlike rewarded can, independently from its position, day by day. These results are consistent with data from the adolescent offspring of mothers exposed to higher doses of THC that exhibited deficits in visual discrimination in the novel object recognition test (NORT) [ 76 ] and alterations in main hippocampal oscillations [ 63 ]. Indeed, if the perirhinal and entorhinal cortices take part in object recognition memory, and particularly in object discrimination when complex stimuli must be processed [ 77 , 78 , 79 ], the hippocampus operates as the hub where direct and indirect projections carrying spatial/object memory information are integrated and encoded [ 80 , 81 , 82 ].…”

Sex Differences in the Behavioural Outcomes of Prenatal Nicotine and Tobacco Exposure

“…Similarly, another study found that PNE males displayed anxiety-like behaviour in the EPM and marble burying test across more exposure periods than did females; additionally, only males showed anxiety-like behaviour in the light/dark box test and Novelty Suppressed Feeding Test (Alkam et al, 2013a). This last finding has also been seen using vapour exposure, with PNE males exhibiting more anxiety-related behaviours than females (Lallai et al, 2022). While males appear to be more vulnerable to anxiety-like behaviours after PNE in preclinical studies (see Table 2), the paucity of research and inconsistent methods make conclusions on sex differences in anxiety-related behaviour after PNE difficult.…”

Prenatal Exposure to Cannabis: Effects on Childhood Obesity and Cardiometabolic Health

“…Of these, 432 were excluded for the following reasons: commentaries or reviews ( n = 71); neurodevelopment, cognitive, or behavioral outcomes ( n = 72); other unrelated health outcomes ( n = 86); studies of hemp oil, synthetic or endogenous cannabinoids, or the endocannabinoid system ( n = 36); polysubstance use or drugs other than cannabis ( n = 24); characteristics or reasons for cannabis use ( n = 43); prevalence studies ( n = 18); biomarker studies ( n = 16); cessation or prevention studies ( n = 9); health policy analyses ( n = 3); effects of pre-conception cannabis use ( n = 3); abstracts or reports presenting insufficient data ( n = 2); and papers focused entirely on unrelated exposures and outcomes ( n = 50). Thus, 47 epidemiologic studies [ 3 , 4 , 14 – 18 , 19 ••, 20 – 28 , 29 •, 30 – 33 , 34 ••, 35 – 58 ] and 12 animal models [ 59 , 60 ••, 61 , 62 , 63 ••, 64 , 65 ••, 66 •, 67 – 70 ] presenting original data met the inclusion criteria for this review.…”