Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8998188 | Neuropharmacology | 2005 | 8 Pages |
Abstract
Prolonged exposure to cannabinoids results in desensitization of cannabinoid receptors. Here, we compared the desensitization produced by the partial agonist, Î9-tetrahydrocannabinol (THC) to that produced by the full agonist Win55,212-2 on cannabinoid-mediated inhibition of glutamatergic synaptic transmission. Synaptic activity between rat hippocampal neurons was determined from network-driven increases in the intracellular Ca2+ concentration ([Ca2+]i spikes). To assess the effects of prolonged treatment, cultures were incubated with cannabinoids, washed in 0.5% fatty-acid-free bovine serum albumin to ensure the removal of the lipophilic drug and then tested for inhibition of [Ca2+]i spiking by Win55,212-2. In control experiments, 0.1 μM Win55,212-2 inhibited [Ca2+]i spiking by 93 ± 5%. Win55,212-2 produced significantly less inhibition of [Ca2+]i spiking following 18-24 h treatment with 1 μM THC (48 ± 5%) or treatment with 1 μM Win55,212-2 (29 ± 6%). Thus, THC produced significantly less functional desensitization than Win55,212-2. The desensitization produced by THC was maximal at 0.3 μM, remained stable between 1 and 7 days of preincubation and shifted the EC50 of acute inhibition by Win55,212-2 from 27 to 251 nM. Differences in the long-term effects of cannabinoid receptor agonists on synaptic transmission may prove important for evaluating their therapeutic and abuse potential.
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Authors
Daniel J. Lundberg, Andrea R. Daniel, Stanley A. Thayer,