The effects of alcohol and cannabinoid exposure during the brain growth spurt on behavioral development in rats

Abstract

Cannabis is the most commonly used illicit drug among pregnant women. Moreover, over half of pregnant women who are consuming cannabis are also consuming alcohol; however, the consequences of combined prenatal alcohol and cannabis exposure on fetal development are not well understood. The current study examined behavioral development following exposure to ethanol (EtOH) and/or CP-55,940 (CP), a cannabinoid receptor agonist. From postnatal days (PD) 4-9, a period of brain development equivalent to the third trimester, Sprague-Dawley rats received EtOH (5.25 g/kg/day) or sham intubation, as well as CP (0.4 mg/kg/day) or vehicle. All subjects were tested on open field activity (PD 18-21), elevated plus maze (PD 25), and spatial learning (PD 40-46) tasks. Both EtOH and CP increased locomotor activity in the open field, and the combination produced more severe overactivity than either exposure alone. Similarly, increases in thigmotaxis in the Morris water maze were caused by either EtOH or CP alone, and were more severe with combined exposure, although only EtOH impaired spatial learning. Finally, developmental CP significantly increased time spent in the open arms on the elevated plus maze. Overall, these data indicate that EtOH and CP produce some independent effects on behavior, and that the combination produces more severe overactivity in the open field. Importantly, these data suggest that prenatal cannabis disrupts development and combined prenatal exposure to alcohol and cannabis may be particularly damaging to the developing fetus, which has implications for the lives of affected individuals and families and also for establishing public health policy.

In utero Δ9-tetrahydrocannabinol exposure confers vulnerability towards cognitive impairments and alcohol drinking in the adolescent offspring: Is there a role for neuropeptide Y?

“…Thus, the augmentation in locomotion could be the result of a decreased habituation to a novel environment compared to the CTRL group. Since habituation per se represents a learning process of the environmental setting, one could speculate that the hyper-locomotor effect observed in this study may underlie a delay in simple learning (Breit et al, 2019) rather than a prominent effect on emotionality. Further investigation of spatial learning abilities (Cannizzaro et al, 2007) of PCE progeny will clarify this point.…”

Sex‐specific behavioural deficits induced at early life by prenatal exposure to the cannabinoid receptor agonist WIN55, 212‐2 depend on mGlu5 receptor signalling

“…Previous findings from our group demonstrated that perinatal exposure to THC (GD 15 to PND 9) altered social play and induced anxiety‐like behaviours in the male rat offspring (Trezza et al, ). Moreover, it has been recently shown that the postnatal exposure to the cannabinoid receptor agonist CP 55,940 from PND 4 to PND 10, a period of brain development equivalent to the third trimester in human, increased the time spent in the open arms of the elevated plus‐maze in offspring of both sexes at prepubertal period (Breit, Zamudio, & Thomas, ). We here showed that prenatally WIN‐exposed animals of both sexes did not exhibit anxious‐like behaviours in the elevated plus‐maze.…”

Combined vapor exposure to THC and alcohol in pregnant rats: Maternal outcomes and pharmacokinetic effects

“…Importantly, the BAC achieved is the critical factor, particularly since alcohol and THC were not administered simultaneously. Moreover, we have previously reported synergistic effects of alcohol and cannabinoids (both on BAC and offspring behavior) when they are administered via different routes during the neonatal period (Breit et al, 2019b(Breit et al, , 2019c, suggesting that synergistic effects are not reliant on a single route of administration. Thus, although this is the first study to administer polydrug exposure via vapor inhalation during the prenatal period, these factors collectively suggest that consequences of prenatal alcohol, as well as the synergistic effects of alcohol and THC, observed in the current study are not due to the route of administration.…”