Developmental and behavioral effects in neonatal and adult mice following prenatal activation of endocannabinoid receptors by capsaicin

• Published in: Acta pharmacologica Sinica 2019-03, Vol.40 (3), p.418-424
• Main Authors: Perchuk, Alex, Bierbower, Sonya M., Canseco-Alba, Ana, Mora, Zoila, Tyrell, Lauren, Joshi, Neal, Schanz, Norman, Gould, Georgianna G., Onaivi, Emmanuel S.
• Format: Article
• Language: English
• Subjects: Activation; Animals; Aversion; Behavior, Animal - drug effects; Benzoxazines - pharmacology; Biomedical and Life Sciences; Biomedicine; Cannabinoid CB1 receptors; Cannabinoid Receptor Agonists - administration & dosage; Cannabinoid Receptor Agonists - pharmacology; Capsaicin; Capsaicin - administration & dosage; Capsaicin - analogs & derivatives; Capsaicin - pharmacology; Capsaicin receptors; Capsazepine; Central nervous system; Conditioning; Embryonic Development - drug effects; Exposure; Female; Gender; Genetic crosses; Gestation; Immunology; Injections, Intraperitoneal; Internal Medicine; Male; Maze Learning - drug effects; Medical Microbiology; Mice; Mice, Inbred BALB C; Morpholines - pharmacology; Naphthalenes - pharmacology; Neonates; Offspring; Pharmacology/Toxicology; Place preference conditioning; Pregnancy; Prenatal experience; Prenatal exposure; Prenatal Exposure Delayed Effects - psychology; Pretreatment; Receptor Cross-Talk; Receptor mechanisms; Receptors, Cannabinoid - metabolism; Righting reflex; Rimonabant - pharmacology; Risk aversion; Therapeutic applications; Transient receptor potential proteins; TRPV Cation Channels - agonists; Vaccine
• ISSN: 1671-4083; 1745-7254
• DOI: 10.1038/s41401-018-0073-z

Despite the apparent abundance of ligand-gated transient receptor potential vanilloid type 1 (TRPV1) and possible cross talk between the endocannabinoid and endovanilloid systems in the central nervous system (CNS), it is unclear what role TRPV1 receptor activation in CNS plays in neurobehavioral development. We previously reported that capsaicin or WIN55212-2 induces risk aversion in the plus-maze test, which was dependent on the gender and mouse strain used. In this study, pregnant BALBc mice were administered capsaicin (1.0 or 4.0 mg/kg, i.p.) during the second week of gestation. Developmental effects of prenatal exposure to capsaicin were assessed in neonates, and behavioral effects were assessed in adult offspring. Gender- and dose-specific variations in ultrasonic vocalizations, weight gain, righting reflex, and general activity of the pups were observed. Prenatal exposure to capsaicin altered plus-maze performance, especially with further exogenous capsaicin challenge. Furthermore, dose- and gender-specific effects were evident in the conditioned place preference/aversion paradigm following conditioning with capsaicin in adult animals. The capsaicin-induced aversion in the plus-maze test was enhanced by WIN55212-2 and blocked by pretreatment with vanilloid antagonist capsazepine or the CB 1 receptor antagonist rimonabant, demonstrating an interaction between the endocannabinoid and endovanilloid systems in CNS. Taken together, the interaction between the endocannabinoid and endovanilloid signaling systems can be exploited for therapeutic applications in health and disease.