 |
||||
|
||||
|
||||
|
||||
|
||||
Previous Article | Next Article
The Journal of Neuroscience, December 15, 1998, 18(24):10663-10671
Suppression of Ethanol-Reinforced Behavior by Naltrexone Is Associated with Attenuation of the Ethanol-Induced Increase in Dialysate Dopamine Levels in the Nucleus Accumbens
Rueben A. Gonzales1 and Friedbert Weiss2 1 Institute for Neuroscience, University of Texas at Austin, Austin, Texas 78712, and 2 Department of Neuropharmacology, The Scripps Research Institute, La Jolla, California 92037
The opiate antagonist naltrexone suppresses ethanol-reinforced behavior in animals and decreases ethanol intake in humans. However, the mechanisms underlying these actions are not well understood. Experiments were designed to test the hypothesis that naltrexone attenuates the rewarding properties of ethanol by interfering with ethanol-induced stimulation of dopamine activity in the nucleus accumbens (NAcc). Simultaneous measures of the effects of naltrexone on dialysate dopamine levels in the NAcc and on operant responding for oral ethanol were used. Male Wistar rats were trained to self-administer ethanol (10-15%, w/v) in 0.2% (w/v) saccharin during daily 30 min sessions and were surgically prepared for intracranial microdialysis. Experiments began after reliable self-administration was established. Rats were injected with naltrexone (0.25 mg/kg, s.c.) or saline and 10 min later were placed inside the operant chamber for a 20 min waiting period with no ethanol available, followed by 30 min of access to ethanol. A transient rise in dialysate dopamine levels was observed during the waiting period, and this effect was not altered by naltrexone. Ethanol self-administration reliably increased dopamine levels in controls. Naltrexone significantly suppressed ethanol self-administration and prevented ethanol-induced increases in dialysate dopamine levels. Subsequent dose-effect analyses established that the latter effect was not merely a function of reduced ethanol intake but that naltrexone attenuated the efficacy of ethanol to elevate dialysate dopamine levels. These results suggest that suppression of ethanol self-administration by opiate antagonists is the result of interference with dopamine-dependent aspects of ethanol reinforcement, although possible additional effects via nondopaminergic mechanisms cannot be eliminated as a factor in opiate antagonist-induced reduction of ethanol intake.
Key words: ethanol; naltrexone; reinforcement; dopamine; microdialysis; nucleus accumbens
Copyright © 1998 Society for Neuroscience 0270-6474/98/182410663-09$05.00/0
This article has been cited by other articles:
J. W. Theile, H. Morikawa, R. A. Gonzales, and R. A. Morrisett
Role of 5-Hydroxytryptamine2C Receptors in Ca2+-Dependent Ethanol Potentiation of GABA Release onto Ventral Tegmental Area Dopamine Neurons
J. Pharmacol. Exp. Ther., May 1, 2009; 329(2): 625 - 633.
[Abstract] [Full Text] [PDF]
R. Spanagel
Alcoholism: A Systems Approach From Molecular Physiology to Addictive Behavior
Physiol Rev, April 1, 2009; 89(2): 649 - 705.
[Abstract] [Full Text] [PDF]
Q. Li, Y. Okada, E. Marczak, W. A. Wilson, L. H. Lazarus, and H. S. Swartzwelder
The Novel {micro}-Opioid Receptor Antagonist, [N-Allyl-Dmt1]Endomorphin-2, Attenuates the Enhancement of GABAergic Neurotransmission by Ethanol
Alcohol Alcohol., January 1, 2009; 44(1): 13 - 19.
[Abstract] [Full Text] [PDF]
C. P O'Brien
Evidence-based treatments of addiction
Phil Trans R Soc B, October 12, 2008; 363(1507): 3277 - 3286.
[Abstract] [Full Text] [PDF]
R. F. Anton
Naltrexone for the Management of Alcohol Dependence
N. Engl. J. Med., August 14, 2008; 359(7): 715 - 721.
[Full Text] [PDF]
M. Schreckenberger, A. Klega, G. Grunder, H.-G. Buchholz, A. Scheurich, R. Schirrmacher, E. Schirrmacher, C. Muller, G. Henriksen, and P. Bartenstein
Opioid Receptor PET Reveals the Psychobiologic Correlates of Reward Processing
J. Nucl. Med., August 1, 2008; 49(8): 1257 - 1261.
[Abstract] [Full Text] [PDF]
H. Myrick, R. F. Anton, X. Li, S. Henderson, P. K. Randall, and K. Voronin
Effect of Naltrexone and Ondansetron on Alcohol Cue-Induced Activation of the Ventral Striatum in Alcohol-Dependent People
Arch Gen Psychiatry, April 1, 2008; 65(4): 466 - 475.
[Abstract] [Full Text] [PDF]
C. P. O'Brien
Prospects for a Genomic Approach to the Treatment of Alcoholism
Arch Gen Psychiatry, February 1, 2008; 65(2): 132 - 133.
[Full Text] [PDF]
F. W. Hopf, M. Martin, B. T. Chen, M. S. Bowers, M. M. Mohamedi, and A. Bonci
Withdrawal From Intermittent Ethanol Exposure Increases Probability of Burst Firing in VTA Neurons In Vitro
J Neurophysiol, October 1, 2007; 98(4): 2297 - 2310.
[Abstract] [Full Text] [PDF]
R. SWIFT
Emerging approaches to managing alcohol dependence
Am. J. Health Syst. Pharm., March 1, 2007; 64(5_Supplement_3): S12 - S22.
[Abstract] [Full Text] [PDF]
K. INGMAN, J. KUPILA, P. HYYTIA, and E. R. KORPI
EFFECTS OF ARIPIPRAZOLE ON ALCOHOL INTAKE IN AN ANIMAL MODEL OF HIGH-ALCOHOL DRINKING
Alcohol Alcohol., July 1, 2006; 41(4): 391 - 398.
[Abstract] [Full Text] [PDF]
C. P. O'Brien
Anticraving Medications for Relapse Prevention: A Possible New Class of Psychoactive Medications
Am J Psychiatry, August 1, 2005; 162(8): 1423 - 1431.
[Abstract] [Full Text] [PDF]
Y.-K. LEE, S.-W. PARK, Y.-K. KIM, D.-J. KIM, J. JEONG, H. MYRICK, and Y.-H. KIM
EFFECTS OF NALTREXONE ON THE ETHANOL-INDUCED CHANGES IN THE RAT CENTRAL DOPAMINERGIC SYSTEM
Alcohol Alcohol., July 1, 2005; 40(4): 297 - 301.
[Abstract] [Full Text] [PDF]
J. MANZANARES, S. ORTIZ, J. M. OLIVA, S. PEREZ-RIAL, and T. PALOMO
INTERACTIONS BETWEEN CANNABINOID AND OPIOID RECEPTOR SYSTEMS IN THE MEDIATION OF ETHANOL EFFECTS
Alcohol Alcohol., January 1, 2005; 40(1): 25 - 34.
[Abstract] [Full Text] [PDF]
C. P. O'BRIEN
The Mosaic of Addiction
Am J Psychiatry, October 1, 2004; 161(10): 1741 - 1742.
[Full Text] [PDF]
A. H. FRIEDLANDER, S. R. MARDER, J. R. PISEGNA, and J. A. YAGIELA
Alcohol abuse and dependence: Psychopathology, medical management and dental implications
J Am Dent Assoc, June 1, 2003; 134(6): 731 - 740.
[Abstract] [Full Text] [PDF]
F. Weiss and L. J. Porrino
Behavioral Neurobiology of Alcohol Addiction: Recent Advances and Challenges
J. Neurosci., May 1, 2002; 22(9): 3332 - 3337.
[Abstract] [Full Text] [PDF]
X. Liu and F. Weiss
Reversal of Ethanol-Seeking Behavior by D1 and D2 Antagonists in an Animal Model of Relapse: Differences in Antagonist Potency in Previously Ethanol-Dependent versus Nondependent Rats
J. Pharmacol. Exp. Ther., March 1, 2002; 300(3): 882 - 889.
[Abstract] [Full Text] [PDF]
F. Weiss, C. S. Maldonado-Vlaar, L. H. Parsons, T. M. Kerr, D. L. Smith, and O. Ben-Shahar
Control of cocaine-seeking behavior by drug-associated stimuli in rats: Effects on recovery of extinguished operant-responding and extracellular dopamine levels in amygdala and nucleus accumbens
PNAS, April 11, 2000; 97(8): 4321 - 4326.
[Abstract] [Full Text] [PDF]
|
|
|
|
 |
|