Figure 2.

Cannabinoids (CBs) prevent the opposite regulation of astroglial connexin-based channels evoked by inflammatory conditions. In activated microglia, endocannabinoids (eCBs) acting on CB₁Rs/CB₂Rs counteract the NF-κβ-dependent release of TNF-α and IL-1β (1). In addition, in activated astrocytes, the stimulation of CB₁Rs could also blunt the NF-κβ-mediated autocrine/paracrine release of TNF-α and IL-1β (2) along with the corresponding activation of TNFR1 (3) and IL1RI/IL1RAcP (4). The latter results in the inhibition of p38 MAP kinase and nitric oxide (NO) production, as well as the consequent reduction in excitotoxic release of gliotransmitters (e.g., glutamate and ATP) through astroglial Cx43 hemichannels (5). In parallel, activation of CB₁Rs/CB₂Rs may neutralize the reduction in gap junction communication (6) evoked by pro-inflammatory conditions (7).