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Sex‐specific behavioural deficits induced at early life by prenatal exposure to the cannabinoid receptor agonist WIN55, 212‐2 depend on mGlu5 receptor signalling
Author(s) -
Manduca Antonia,
Servadio Michela,
Melancia Francesca,
Schiavi Sara,
Manzoni Olivier J.,
Trezza Viviana
Publication year - 2020
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/bph.14879
Subject(s) - cannabinoid receptor , offspring , agonist , cannabinoid , psychology , medicine , receptor , endocrinology , pregnancy , physiology , developmental psychology , biology , genetics
Background and Purpose Marijuana is the illicit drug most commonly used among pregnant and breastfeeding women. Different studies reported long‐term adverse effects induced by in utero exposure to the main component of marijuana, Δ 9 ‐tetrahydrocannabinol (THC), both in rodents and in humans. However, little is known about any potential sex‐dependent effects of marijuana consumption during pregnancy on newborns at early developmental ages. Experimental Approach We studied the effects of prenatal exposure to the cannabinoid receptor agonist WIN55,212‐2 (WIN; 0.5 mg·kg −1 from GD5 to GD20) on the emotional reactivity and cognitive performance of male and female rat offspring from infancy through adolescence and tested the role of mGlu 5 receptor signalling in the observed effects. Key Results Prenatally WIN‐exposed male infant pups emitted less isolation‐induced ultrasonic vocalizations compared with male control pups, when separated from the dam and siblings and showed increased locomotor activity while females were spared. These effects were normalized when male pups were treated with the positive allosteric modulator of mGlu 5 receptor CDPPB. When tested at the prepubertal and pubertal periods, WIN‐prenatally exposed rats of both sexes did not show any difference in social play behaviour, anxiety and temporal order memory. Conclusions and Implications We reveal a previously undisclosed sexual divergence in the consequences of fetal cannabinoids on newborns at early developmental ages, which is dependent on mGlu 5 receptor signalling. These results provide new impetus for the urgent need to investigate the functional and behavioural substrates of prenatal cannabinoid exposure in both the male offspring and the female offspring.