Prenatal alcohol and tetrahydrocannabinol exposure: Effects on spatial and working memory

Abstract

Introduction: Alcohol and cannabis are widely used recreational drugs that can negatively impact fetal development, leading to cognitive impairments. However, these drugs may be used simultaneously and the effects of combined exposure during the prenatal period are not well understood. Thus, this study used an animal model to investigate the effects of prenatal exposure to ethanol (EtOH), Δ-9-tetrahydrocannabinol (THC), or the combination on spatial and working memory.

Methods: Pregnant Sprague-Dawley rats were exposed to vaporized ethanol (EtOH; 68 ml/h), THC (100 mg/ml), the combination, or vehicle control during gestational days 5-20. Adolescent male and female offspring were evaluated using the Morris water maze task to assess spatial and working memory.

Results: Prenatal THC exposure impaired spatial learning and memory in female offspring, whereas prenatal EtOH exposure impaired working memory. The combination of THC and EtOH did not exacerbate the effects of either EtOH or THC, although subjects exposed to the combination were less thigmotaxic, which might represent an increase in risk-taking behavior.

Discussion: Our results highlight the differential effects of prenatal exposure to THC and EtOH on cognitive and emotional development, with substance- and sex-specific patterns. These findings highlight the potential harm of THC and EtOH on fetal development and support public health policies aimed at reducing cannabis and alcohol use during pregnancy.

Keywords: alcohol; cannabis; combined exposure; pregnancy; rodents; spatial memory; vaping; working memory.

Figure 1

Offspring exposed to prenatal THC weighed less than those not exposed to prenatal THC throughout behavioral testing, although these effects became less pronounced with age [females (A,C); males (B,D)].

Figure 2

Female offspring prenatally exposed to THC alone required longer path lengths to find the hidden platform during the visuospatial memory task (A,C). There were no effects of prenatal exposure on performance among male offspring (B,D). *Air + THC > Air + Vehicle, p < 0.05; **Air + THC > EtOH + Vehicle, p < 0.05; ***Air+THC > all other groups, p < 0.01.

Figure 3

Female offspring prenatally exposed to alcohol alone had significantly larger heading angles (impaired performance) compared to controls (A,C). Heading angle did not differ among groups of male offspring (B,D). *EtOH+Vehicle > Air+Vehicle, p < 0.05.

Figure 4

Female offspring exposed to either THC alone or alcohol alone were more thigmotaxic compared to those exposed to the combination or controls (A,C). No differences were observed among male offspring (B,D). *EtOH + Vehicle > EtOH + THC, p < 0.05; **Air + THC > EtOH + THC and Air + Vehicle, p’s < 0.05; ***all other groups > EtOH + THC, p’s < 0.05; ****Air + THC > EtOH+THC, p’s < 0.05.

Figure 5

Female offspring exposed to THC spent less time in the Target quadrant and more time in the Opposite quadrant than non-exposed offspring (A). Neither prenatal THC nor alcohol significantly affected spatial memory among male offspring (B). *THC < no THC, p < 0.05; **THC > no THC, p < 0.01.

Figure 6

Female offspring exposed to prenatal THC showed impaired performance during the probe trial, spending less time in the target area (A) and fewer passes through the target (C). Female offspring exposed to combined alcohol and THC prenatally were less thigmotaxic (E). No differences were observed among male offspring (B,D,F). *THC < no THC, p < 0.01; **EtOH + THC < EtOH + Vehicle and Air + THC, p’s < 0.05.

Figure 7

Male offspring exposed to prenatal alcohol exposure traveled longer path lengths on the first day of testing (B), whereas female offspring with prenatal alcohol exposure traveled shorter path lengths during the latter 60-s ITI test trials (A). However, offspring prenatally exposed to alcohol had less memory savings between the training and test trials, an effect driven by the female offspring (C,D). *EtOH < no EtOH, p’s < 0.05; **EtOH > no EtOH, p < 0.05; ⁺EtOH < no EtOH, p = 0.06.

Figure 8

Male offspring exposed to prenatal THC swam slower during training sessions than those not exposed to THC (B). Swim speed did not differ among groups of female offspring (A). *THC < no THC, p < 0.05; ⁺THC < no THC, p = 0.06.

Figure 9

Female offspring exposed to either alcohol or THC prenatally spent more time in thigmotaxis on the 1st day of 0-s ITI training (A). In contrast, females exposed to the combination of prenatal alcohol and THC spent less time in thigmotaxis on the 1st day of 60-s ITI training (4th day; A). There were no significant differences during testing in females (C). No significant differences were observed among male offspring (B,D). *EtOH + Vehicle and Air + THC > EtOH + THC and Air + Vehicle, p < 0.05; **EtOH + THC < all other groups, p = 0.05.