Cannabinoid CB(1) receptor expression and affinity in the rat hippocampus following bilateral vestibular deafferentation.
Numerous studies have shown that bilateral vestibular deafferentation (BVD) results in spatial memory deficits and hippocampal dysfunction in rats and humans. Since cannabinoid CB(1) receptors are well known to regulate synaptic plasticity in the hippocampus, we investigated whether BVD resulted in changes in CB(1) receptor expression and affinity in the rat hippocampus at 1, 3 and 7 days post-surgery, using a combination of Western blotting and radioligand binding. Using Western blotting, we found that CB(1) receptor expression was significantly lower in BVD animals compared to sham controls only in the CA3 area across the 3 time points (P=0.03). CB(1) receptor expression decreased significantly over time for both the BVD and sham animals (P=0.000). The radioligand binding assays showed no significant change in the IC(50) of the CB(1) receptor for the cannabinoid CB(1)/CB(2) receptor agonist, WIN55,212-2. These results suggest that the CB(1) receptor down-regulates in the CA3 region of the hippocampus following BVD, but with no changes in the affinity of the CB(1) receptor for WIN55,212-2.
Department of Pharmacology and Toxicology, School of Medical Sciences, University of Otago Medical School, P.O. Box 913, Dunedin, New Zealand.
Jean Ha
JH
Baek
Yiwen
Y
Zheng
Cynthia L
CL
Darlington
Paul F
PF
Smith
D000818:Animals; D019771:Axotomy; D048588:Benzoxazines / Q000494:pharmacology; D015153:Blotting, Western; D002121:Calcium Channel Blockers / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009025:Morpholines / Q000494:pharmacology; D009281:Naphthalenes / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D043884:Receptor, Cannabinoid, CB1 / Q000096:biosynthesis*; D014722:Vestibule, Labyrinth / Q000502:physiology* / Q000601:surgery
D048588:Benzoxazines; D002121:Calcium Channel Blockers; D009025:Morpholines; D009281:Naphthalenes; D043884:Receptor, Cannabinoid, CB1; C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone