Neuroscience 2002 Abstract
| Presentation Number: | 500.4 |
|---|---|
| Abstract Title: | AGS3 Regulates Cocaine Seeking and Behavioral Sensitization Following Extended Withdrawal. |
| Authors: |
Bowers, M. S.*1
; Lapish, C. C.1
; Lake, R. W.1
; McFarland, K.1
; Lanier, S. M.2
; Kalivas, P. W.1
1Physiology & Neuroscience , Medical University South Carolina, Charleston, SC 2Pharmacology & Experimental Therapeutics, LSU Health Sciences, New Orleans, LA |
| Primary Theme and Topics |
Neurological and Psychiatric Conditions - Addiction and Drugs of Abuse -- Cocaine |
| Secondary Theme and Topics | Synaptic Transmission and Excitability<br />- G-Protein Linked Receptors<br />-- Other |
| Session: |
500. Addiction and drugs of abuse: cocaine IV Poster |
| Presentation Time: | Tuesday, November 5, 2002 11:00 AM-12:00 PM |
| Location: | Hall A2-B3 Z-59 |
| Keywords: | G PROTEIN, GENE EXPRESSION, REINSTATEMENT, METABOTROPIC RECEPTOR |
Withdrawal from repeated cocaine dysregulates Gi-protein signaling. The recently discovered G-protein dissociation inhibitor, AGS3, is selectively upregulated in the rat prefrontal cortex and accumbens core following extended withdrawal (3 wks) from repeated cocaine (7 daily injections). AGS3 can bind to and stabilize up to 4 Giαs, independent of the βγ complex, preferentially in the GDP bound conformation. Aggregating Giα in its inactive conformation may therefore potentiate signaling via βγ-mediated effectors. Interestingly, preventing the withdrawal-induced rise in prefrontal cortex AGS3 expression with antisense oligonucleotides also prevents both the expression of behavioral sensitization to cocaine and the reinstatement of drug seeking following administration of a cocaine prime (10 mg/kg; ip). Furthermore, the sensitized behavioral response returns following oligonucleotide washout. AGS3 may represent a novel mode of action for Gi coupled receptors in the rat prefrontal cortex following extended withdrawal from repeated cocaine, as its upregulation is required for the expression of behavioral sensitization and reinstatement of cocaine seeking.
Supported by DA03906, DA12513 (PWK) and a NASA predoctoral fellowship (MSB)
Sample Citation:
[Authors]. [Abstract Title]. Program No. XXX.XX. 2002 Neuroscience Meeting Planner. Orlando, FL: Society for Neuroscience, 2002. Online.
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