Evidence For Functional Role Of CB1 Cannabinoid Receptors In The Mammalian Cone Pathway

Abstract

Purpose: : CB₁ cannabinoid receptor immunoreactivity has been documented in the vertebrate retina. We investigated the retinal function of transgenic mice lacking CB₁ receptors (CB₁-/-) or monoacylglycerol lipase (MGL-/-), the enzyme involved in the breakdown of endogenous cannabinoid 2-arachidonoyl glycerol (2AG).

Methods: : Full-field photopic flash electroretinograms (ERG) were recorded with DTL electrodes, differentially between the two eyes from anesthetized (ketamine 80 mg/kg, xylazine 10 mg/kg) wild type (WT), CB₁-/- and MGL-/- mice using an ESPION system. Pupils were dilated with phenylephrine HCL (2.5%) and accommodation blocked with tropicamide (1%). The cornea was kept moist with methylcellulose (1%) under custom contact lenses. Using blue light (640 nm, 40 nm ½ band width), 0.7 to 171 (P) cd.s/m² test flashes were delivered on a 112 (P) cd/m² background.

Results: : ERG waveforms of WT, CB₁-/- and MGL-/- showed a- and b-waves that increased in amplitude with flash intensity. For the 171 (P) cd.s/m² test flash, the average a-wave implicit time of MGL-/- was 12.8 ms, shorter than those of WT (19 ms, p<0.0013) and CB₁-/- (21.8 ms, p<0.00079). The average b-wave implicit time of CB₁-/- was 87.3 ms and delayed relative to WT (54.3 ms, p<0.00037) and MGL-/- (32ms, p<0.000072). The b-wave of CB₁-/- also took a longer time to recover as indicated by the ½ band width of 129 ms relative to those of the WT (37 ms) and MGL -/- (27 ms) groups. The b-wave of MGL-/- was followed by a large negative potential. The a- and b-wave amplitudes were not significantly different for the 3 groups. However, the intensity response function of the b-wave amplitude indicated a smaller semi-saturation constant [14 (P) cd.s/m²] with a slope of 1.75 for CB1 -/- relative to WT [67 (P) cd.s/m², slope 0.83] and MGL -/- [20 (P) cd.s/m², slope 2.1].

Conclusions: : The significant alterations in the photopic flash ERG responses of transgenic mice lacking CB₁ receptors or the enzyme MGL provide further evidence for a functional role of CB₁ receptors and endogenous cannabinoids in retinal information processing.

Keywords: electrophysiology: non-clinical • electroretinography: non-clinical • retina