Neuroscience 2004 Abstract
| Presentation Number: | 961.16 |
|---|---|
| Abstract Title: | A novel technique to study CB1 cannabinoid receptor internalization in cultured hippocampal neurons. |
| Authors: |
Myoga, M.*1
; Chris, K. S.2,3
; Celver, J.4
; Mackie, K.1,2,3
1Neurobiology, Univ Washington, Seattle, WA 2Physiology & Biophysics, Univ Washington, Seattle, WA 3Anesthesiol., Univ Washington, Seattle, WA 4Pharmacol., Univ Washington, Seattle, WA |
| Primary Theme and Topics |
Synaptic Transmission and Excitability - G-Protein linked Receptors -- Other |
| Session: |
961. GPCR-Linked Receptors: Other Poster |
| Presentation Time: | Wednesday, October 27, 2004 4:00 PM-5:00 PM |
| Location: | San Diego Convention Center - Hall A-H, Board # N5 |
| Keywords: | PRESYNAPTIC, IMAGING |
CB1 cannabinoid receptors are G-protein coupled receptors enriched on presynaptic processes in several central nervous system regions including those that underlie analgesia, cognition, motor control, and memory. CB1 receptors are the primary target of delta-9-tetrahydrocannabinol, (THC) the major psychoactive constituent of cannabis, and are also activated by endogenous cannabinoids. Tolerance develops following chronic THC use and CB1 receptor internalization is a process likely to contribute to tolerance. It is known that following sustained agonist treatment, heterologously expressed CB1 receptors internalize via a classical clathrin-mediated pathway. The aim of this study was to develop and characterize a technique to investigate the kinetics and mechanisms of CB1 internalization in primary hippocampal cultures using immunocytochemistry and confocal microscopy. During brief administration of the synthetic CB1 agonist CP55,940, CB1 staining in boutons became increasingly punctuate. This was quantified by determining the variance of pixel intensity throughout the bouton. During prolonged agonist administration CB1 accumulated in perisomatic regions, likely targeted to a degradative pathway. These robust changes were concentration dependent and were blocked by the CB1 specific antagonist SR141716A, suggesting that CB1 activation mediates this process. We will use this system to investigate key steps and molecules involved in CB1 internalization in neurons. The results from these studies will contribute to our understanding of the molecular basis of tolerance to cannabis.
Supported by DA11322, DA00286, DA13410, HHMI, and UW Mary Gates Endowment
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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