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Type: Journal article
Title: The glial activation inhibitor AV411 reduces morphine-induced nucleus accumbens dopamine release
Author: Bland, S.
Hutchinson, M.
Maier, S.
Watkins, L.
Johnson, K.
Citation: Brain, Behavior, and Immunity, 2009; 23(4):492-497
Publisher: Academic Press Inc
Issue Date: 2009
ISSN: 0889-1591
Statement of
Sondra T. Bland, Mark R. Hutchinson, Steven F. Maier, Linda R. Watkins, Kirk W. Johnson
Abstract: Glial activation has recently been discovered to modulate several effects of morphine, including analgesia, tolerance, and dependence. The present studies extend this line of investigation by exploring whether glial activation may also affect extracellular levels of dopamine (DA) in the nucleus accumbens (NAc) shell, a neurochemical corollary of morphine-induced drug reward, during a challenge dose of morphine in experiments both with and without precipitated withdrawal. Morphine or vehicle was administered s.c. for 4 days (starting at 15 mg/kg/day up to 20 mg/kg/day), and the glial activation inhibitor AV411 (7.5 mg/kg) or vehicle was administered twice daily. A challenge dose of morphine (22.5 mg/kg) or saline was then given during dialysis. In the first experiment, naloxone (10 mg/kg) was administered 1h after morphine during dialysis in AV411- or vehicle-treated rats, and behavioral signs of somatic withdrawal were assessed during microdialysis. In the second experiment, using the same dosing regimen, sampling continued 3 h after morphine or saline in AV411- or vehicle-treated rats. NAc DA increased in vehicle-treated rats significantly more than in AV411-treated rats before naloxone treatment, and withdrawal symptoms were significantly reduced in AV411-treated rats. The decrease in morphine-induced NAc DA by AV411 was persistent, lasting 3+h post-morphine. These results indicate that glial activation contributes to the effects of morphine on NAc DA, which is associated with somatic signs of precipitated withdrawal.
Keywords: Opioid
Nucleus accumbens
Description: Copyright © 2009 Elsevier Inc. All rights reserved.
DOI: 10.1016/j.bbi.2009.01.014
Appears in Collections:Aurora harvest
Pharmacology publications

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