In rats, intrauterine exposure to cannabinoid affected cardiorespiratory function and sleep quality in adulthood

Brazilian researchers analyzed behavioral and physiological factors in animals whose mothers received a synthetic substance that activates the same receptors as marijuana during pregnancy. The consequences were different in males and females.

By André Julião  |  Agência FAPESP – Scientists who exposed pregnant rats to a synthetic cannabinoid that activates the same receptors in the brain as marijuana detected effects of the drug on their offspring, such as cardiovascular problems in females and augmented susceptibility to panic attacks in males, and showed that these adverse effects persisted into adulthood. An article on the study is published in the American Journal of Physiology – Lung Cellular and Molecular Physiology. The findings serve as a precautionary note on the medicinal or recreational use of cannabis during pregnancy, the authors conclude.

The study was conducted with FAPESP’s support by researchers affiliated with São Paulo State University (UNESP) and the University of São Paulo (USP) in Brazil. Previous research by the same group demonstrated the effects of intrauterine exposure to the cannabinoid on newborn and young rats (read more at: agencia.fapesp.br/41209). 

“We observed long-term alterations to behavior and above all to cardiorespiratory function in the animals that were exposed to the cannabinoid while they were still in the womb. The alterations were different in males and females,” said Luis Gustavo Patrone, first author of the article. The study was part of his PhD research, which was supported by a scholarship from FAPESP while he was a doctoral candidate at the School of Agricultural and Veterinary Sciences (FCAV-UNESP) in Jaboticabal, São Paulo state, where he is now a postdoctoral fellow. 

In contrast with the newborns in the previous study, the adult individuals (80 days old) analyzed in this latest trial did not display alterations to baseline respiration, possibly owing to some unknown compensation mechanism during postnatal development.

A finding that did not vary from one study to the other was that intrauterine exposure to the cannabinoid increased the adult males’ respiratory sensitivity to carbon dioxide (CO₂). The opposite outcome was observed in the females.

“In humans, heightened sensitivity to CO₂ can trigger panic attacks with shortness of breath and a false suffocation alarm. In the animals in our experiment, this type of behavior consisted of attempts to escape from the chamber,” said Luciane Gargaglioni, last author of the article and a professor at FCAV-UNESP.

Cardiovascular function and sleep

The researchers also analyzed cardiovascular factors and sleep quality in the animals, concluding that exposure to the cannabinoid during fetal development led to a propensity to experience cardiovascular dysfunction in adulthood, with hypertension and tachycardia being most frequently identified in females.

Sleep quality deteriorated most in males, which experienced sleep fragmentation due to frequent wakefulness episodes. “They slept less, considering the sum total of sleep episodes,” Patrone said. Sleep quality also deteriorated in females, but less severely.

“Most scientific studies assess parameters in males only, assuming that the results will be valid for both sexes, but in our lab we always make the distinction and the responses are often quite different, as in this study,” Gargaglioni said.

A possible explanation for the difference between outcomes in males and females may be the action of sex hormones. In females, estrogen is known to be neuroprotective and may ward off the harmful effects of the cannabinoid on their brains.

In addition, the mammalian respiratory system is known to develop more slowly in males, occurring mainly when testosterone levels peak during masculinization and formation of sexual organs. Later maturation of the lungs, and of the brain regions responsible for controlling respiratory function, probably made the males more vulnerable to the adverse effects of the cannabinoid.

The authors point out that observed postpartum maternal behavior did not exhibit differences in maternal care of offspring due to exposure to the cannabinoid during pregnancy compared with the control group, which did not receive the substance. 

The article “Long-term effects on cardiorespiratory and behavioral responses in male and female rats prenatally exposed to cannabinoid” is at: journals.physiology.org/doi/abs/10.1152/ajplung.00042.2024.