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

Abstract

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 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.

Capsaicin Causes Vasorelaxation of Rat Aorta through Blocking of L-type Ca2+ Channels and Activation of CB1 Receptors

“…Moreover, TRPV1 receptors and cannabinoid receptors share some signaling pathways in various cell types [ 30 , 31 , 32 , 33 , 34 , 35 ]. Several groups have demonstrated the activation of TRPV1 receptors by endocannabinoids, so there is a possibility that Capsaicin may activate cannabinoid receptors as well [ 32 , 36 ]. In this way, the effect of Capsaicin was explored after inhibiting CB 1 or CB 2 receptors with specific antagonists.…”

Cannabis, cannabinoid receptors, and endocannabinoid system: yesterday, today, and tomorrow

“…The possible cross-talk between the endocannabinoid and endovanilloid (vanilloid type 1, TRPV1) systems is discussed in the article "Developmental and behavioral effects in neonatal and adult mice following prenatal activation of endocannabinoid receptors by capsaicin". Here the authors found that prenatal exposure to capsaicin altered plus-maze performance, and the conditioned place preference/aversion paradigm following conditioning with capsaicin in adult animals [13]. Based on available data they suggest that the interaction between the endocannabinoid and endovanilloid signaling systems can be exploited for therapeutic applications in health and disease.…”

Depression as a Neuroendocrine Disorder: Emerging Neuropsychopharmacological Approaches beyond Monoamines

“…Functionally, reward processing involves two interrelated components: motivational processing, which centers attention and behavior on rewarding stimuli and fundamentally involves dopaminergic neurotransmission; and hedonic processing, which mediates the pleasurable reaction to these stimuli, and involves GABAergic, opioid, endocannabinoid (EC), and endovanilloid (EV) signaling throughout the NAcc, ventral pallidum, insular cortex, and orbitofrontal cortex [224, 225]. The crosstalk among these systems is complex and remains to be fully elucidated [226, 227]. However, specific components in these circuits have already emerged as potential targets in the neuropsychopharmacological approach to depression (Figure 4).…”