Neuroscience 2005 Abstract
| Presentation Number: | 563.8 |
|---|---|
| Abstract Title: | Disruption of protein--protein coupling between PTEN and 5-HT<sub>2C</sub> receptor suppresses marijuana-rewarding effects. |
| Authors: |
Ji, S.*1
; Zhang, Y.1
; Van Cleemput, J.1
; Jiang, W.1
; Wan, Q.2
; Backstrom, J. R.3
; Zhang, X.1
1Neuropsychiat Res Unit, Department of Psychiatry, Univ. of Saskatchewan, Saskatoon, Canada 2ON, 103 Wiggins Road, S7N 5E4, 3Canada, 103 Wiggins Road, S7N 5E4, |
| Primary Theme and Topics |
Disorders of the Nervous System - Addiction and Drugs of Abuse -- Cannabinoids |
| Secondary Theme and Topics | Neural Excitability, Synapses, and Glia: Cellular Mechanisms<br />- G-Protein Linked Receptors<br />-- Serotonin receptors |
| Session: |
563. Cannabinoids Poster |
| Presentation Time: | Monday, November 14, 2005 4:00 PM-5:00 PM |
| Location: | Washington Convention Center - Hall A-C, Board # UU80 |
| Keywords: | serotonin, conditioned place preference , cannabinoid, drug addiction |
The widespread distribution of the tumor suppressor PTEN (phosphatase and tensin homologue deleted on chromosome 10) in adult brain suggests its important role in a broad range of brain function, but the exact role remains largely unknown. Here we show evidence supporting a direct protein-protein coupling of PTEN with the 3L4F motif in the third intracellular loop of 5-HT2c receptor (5-HT2cR) in PC12 cells. We then design the membrane permeable peptide Tat-3L4F that is able to penetrate the blood brain barrier to disrupt the protein-protein coupling between PTEN and 5-HT2cR in the brain. Systemic Tat-3L4F or the 5-HT2cR agonist Ro600175 (3 mg/kg) suppresses the increased firing rate of VTA (ventral tegmental area) dopamine neurons induced by delta-9-tetrahydrocannabinol (THC), the psychoactive ingredient of marijuana. Using the conditioned place preference paradigm for behavioural testing, we further show that systemic Tat-3L4F or Ro600175 (3 mg/kg) block the rewarding effects of THC, which is abolished by the 5-HT2cR antagonist SB242084. Other behavioral tests show that Ro600175 (3 mg/kg), but not Tat-3L4F, produces significant anxiogenic effects, penile erection, hypophagia and motor functional suppression. These results suggest a novel strategy for treating drug addiction with Tat-3L4F.
Supported by postdoctoral fellowship awards from the Saskatchewan Health Research Foundation to S.J. and W.J. and by a grant from the Canadian Institutes of Health Research (CIHR) awarded to X.Z who is the recipient of the CIHR New Investigator Award.
Supported by postdoctoral fellowship awards from the Saskatchewan Health Research Foundation to S.J. and W.J. and by a grant from the Canadian Institutes of Health Research (CIHR) awarded to X.Z who is the recipient of the CIHR New Investigator Award.
Sample Citation:
[Authors]. [Abstract Title]. Program No. XXX.XX. 2005 Neuroscience Meeting Planner. Washington, DC: Society for Neuroscience, 2005. Online.
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