| First Author | Dvorakova M | Year | 2021 |
| Journal | Br J Pharmacol | Volume | 178 |
| Issue | 7 | Pages | 1588-1604 |
| PubMed ID | 33491188 | Mgi Jnum | J:321777 |
| Mgi Id | MGI:6871796 | Doi | 10.1111/bph.15383 |
| Citation | Dvorakova M, et al. (2021) SGIP1 is involved in regulation of emotionality, mood, and nociception and modulates in vivo signalling of cannabinoid CB1 receptors. Br J Pharmacol 178(7):1588-1604 |
| abstractText | BACKGROUND AND PURPOSE: Src homology 3-domain growth factor receptor-bound 2-like endophilin interacting protein 1 (SGIP1) interacts with cannabinoid CB1 receptors. SGIP1 is abundantly and principally expressed within the nervous system. SGIP1 and CB1 receptors co-localize in axons and presynaptic boutons. SGIP1 interferes with the internalization of activated CB1 receptors in transfected heterologous cells. Consequently, the transient association of CB1 receptors with beta-arrestin2 is enhanced and prolonged, and CB1 receptor-mediated ERK1/2 signalling is decreased. Because of these actions, SGIP1 may modulate affect, anxiety, pain processing, and other physiological processes controlled by the endocannabinoid system (ECS). EXPERIMENTAL APPROACH: Using a battery of behavioural tests, we investigated the consequences of SGIP1 deletion in tasks regulated by the ECS in SGIP1 constitutive knockout (SGIP1(-/-) ) mice. KEY RESULTS: In SGIP1(-/-) mice, sensorimotor gating, exploratory levels, and working memory are unaltered. SGIP1(-/-) mice have decreased anxiety-like behaviours. Fear extinction to tone is facilitated in SGIP1(-/-) females. Several cannabinoid tetrad behaviours are altered in the absence of SGIP1. SGIP1(-/-) males exhibit abnormal behaviours on Delta(9) -tetrahydrocannabinol withdrawal. SGIP1 deletion also reduces acute nociception, and SGIP1(-/-) mice are more sensitive to analgesics. CONCLUSION AND IMPLICATIONS: SGIP1 was detected as a novel protein associated with CB1 receptors, and profoundly modified CB1 receptor signalling. Genetic deletion of SGIP1 particularly affected behavioural tests of mood-related assessment and the cannabinoid tetrad. SGIP1(-/-) mice exhibit decreased nociception and augmented responses to CB1 receptor agonists and morphine. These in vivo findings suggest that SGIP1 is a novel modulator of CB1 receptor-mediated behaviour. |
