Abstract
BACKGROUND AND PURPOSE:
Anatomical, biochemical and pharmacological evidences suggest the existence of a cross-talk between the orexinergic and the endocannabinoid system. While orexin receptor 1 (OX1) modulates the reinforcing properties of cannabinoids, the participation of orexins in the acute pharmacological effects of Δ9-tetrahydrocannabinol (THC) remains unexplored.
EXPERIMENTAL APPROACH:
We assessed the possible role of orexins in THC-induced hypolocomotion, hypothermia, antinociception, anxiolytic- and anxiogenic-like effects, and memory impairment. Selective OX1 and OX2 antagonists, OX1 knockout (KO) mice as well as prepro-orexin (PPO) KO mice were used as pharmacological and genetic approaches. CB1 receptor levels in control and PPO KO mice were evaluated by immunoblot analysis. The expression of c-Fos after THC treatment was analyzed in several brain areas in wild-type and mice lacking the PPO gene.
KEY RESULTS:
The hypothermia, supraspinal antinociception and anxiolytic-like effects induced by THC were modulated by orexins through OX2 signalling. OX1 did not seem to be involved in these THC responses. No differences in CB1 receptor levels were found between wild-type and PPO KO mice. THC-induced c-Fos expression was reduced in the central amygdala, medial preoptic area and lateral septum in these mutant mice.
CONCLUSIONS AND IMPLICATIONS:
Our results provide new findings to further clarify the interaction between orexins and cannabinoids. OX1 and OX2 are differently implicated in the pharmacological effects of cannabinoids.
This article is protected by copyright. All rights reserved.
- PMID:
- 26799708
- [PubMed – as supplied by publisher]
