Neuroscience 2004 Abstract
| Presentation Number: | 961.18 |
|---|---|
| Abstract Title: | Downregulation of brain CB<sub>1</sub> cannabinoid receptor binding sites without decreased CB<sub>1</sub> protein after chronic Δ<sup>9</sup>-tetrahydrocannabinol administration. |
| Authors: |
Selley, D. E.*1
; Schechter, N. S-.1
; Sylvester, J. L-.1
; Martin, B. R-.1
; Sim-Selley, L. J-.1
1Dept. Pharmacol & Toxicol, VA Commonwealth Univ, Richmond, VA |
| Primary Theme and Topics |
Synaptic Transmission and Excitability - G-Protein linked Receptors -- Other |
| Secondary Theme and Topics | Synaptic Transmission and Excitability<br />- Intracellular Signaling Pathways<br />-- Other |
| Session: |
961. GPCR-Linked Receptors: Other Poster |
| Presentation Time: | Wednesday, October 27, 2004 2:00 PM-3:00 PM |
| Location: | San Diego Convention Center - Hall A-H, Board # N5 |
| Keywords: | G-protein, desensitization, hippocampus, striatum |
CB1 cannabinoid receptors are G-protein-coupled receptors that primarily activate Gi/Go. CB1 receptors are abundant in the CNS, where they mediate the effects of psychoactive cannabinoids such as Δ9-tetrahydrocannabinol (THC) and endocannabinoid lipid messengers. Our previous studies have shown that chronic THC administration in mice produces widespread desensitization and downregulation of CB1 receptors in the CNS, with hippocampus exhibiting profound CB1 receptor adaptation. The present study examined the mechanism of CB1 receptor downregulation in brain. THC was administered by subcutaneous injection twice daily using an escalating dosage paradigm in which the dose was ramped from 10 to 160 mg/kg over 15 days. Results showed that CB1 receptor-mediated G-protein activation was reduced by approximately 50% in THC-treated mice compared to control, as determined by agonist-stimulated [35S]GTPγS binding in hippocampal or striatal membranes. CB1 receptor binding sites measured with the antagonist [3H]SR141716A were similarly decreased. This decrease was not due to residual THC in the tissue, as alteration in the Bmax but not the KD value of [3H]SR141716A was observed. Examination of CB1 mRNA by northern blot analysis showed a paradoxical increase. Furthermore, levels of CB1 receptor protein measured by immunoblot analysis were not decreased in THC-treated compared to vehicle-treated mice, and this result was confirmed in situ by immunocytochemical staining of brain sections. These results demonstrate chronic THC-induced downregulation of functional CB1 receptors that apparently does not result from decreased transcription nor increased degradation of the receptor.
Supported by NIDA
Sample Citation:
[Authors]. [Abstract Title]. Program No. XXX.XX. 2004 Neuroscience Meeting Planner. San Diego, CA: Society for Neuroscience, 2004. Online.
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