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

Abstract

IntroductionAlcohol 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.MethodsPregnant 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.ResultsPrenatal 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.DiscussionOur 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.

Prenatal ethanol and cannabis exposure have sex‐ and region‐specific effects on somatostatin and neuropeptide Y interneurons in the rat hippocampus

“…Notably, significant behavioral effects on the Morris water maze were only seen among female subjects (Lei et al, 2023), in contrast with the present study that found changes in interneurons in both sexes. Nevertheless, there are some parallels between drug effects on Morris water maze performance and hippocampal interneuron pathology.…”

“…It is interesting that prenatal THC exposure (particularly alone) produced some of the most robust changes in SOM cells. On the Morris water maze, littermates exposed to prenatal THC showed the most severe impairments in spatial learning and memory (Lei et al, 2023). In addition, the pattern of significant changes in NPY cells exposed to either prenatal THC or alcohol alone, but not the combination, is also consistent with changes in anxiety-related behaviors (thigmotaxis) within the Morris water maze (Lei et al, 2023), as subjects exposed to either drug alone were more thigmotaxic, but those exposed to the combination were least thigmotaxic.…”

“…With the legalization of cannabis in many jurisdictions, there has also been a persistent increase in the simultaneous use of alcohol and cannabis in young adults between 19 and 30 years of age, the demographics associated with peak fertility (Subbaraman & Kerr, 2015). Since prenatal ethanol exposure is already known to cause learning and memory deficits, and as alcohol and cannabis directly impair working and spatial memory in adults, it is likely that concurrent prenatal exposure will produce some degree of memory deficit (Hayatbakhsh et al, 2012;Khemiri et al, 2019;Lei et al, 2023;Sweeney et al, 2018). As the hippocampus plays a central role in learning and memory processes, it is a prominent candidate system to study for cellular and molecular changes (Reid et al, 2020).…”

Prenatal Cannabinoid Exposure Elicits Memory Deficits Associated with Reduced PSA-NCAM Expression, Altered Glutamatergic Signaling, and Adaptations in Hippocampal Synaptic Plasticity

“…We selected male mice because prior studies indicated that synaptic plasticity [55] and hippocampal function in males [56][57][58], but not females [55,58], were altered by PCE. Likewise, previous studies suggest PCE impairs spatial memory in males [58,59] but not females [58], though a more recent study revealed a deficit in females [60]. We will address sex as a biological variable in future studies.…”