JPET Assistant Professor of Medicine (Clinician-Educator)

Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Czoty, P. W.
Right arrow Articles by Howell, L. L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Czoty, P. W.
Right arrow Articles by Howell, L. L.

Vol. 300, Issue 3, 831-837, March 2002

Serotonergic Attenuation of the Reinforcing and Neurochemical Effects of Cocaine in Squirrel Monkeys

Paul W. Czoty1 , Brett C. Ginsburg and Leonard L. Howell

Yerkes Regional Primate Research Center (P.W.C., B.C.G., L.L.H.), Department of Psychiatry and Behavioral Sciences (L.L.H.), and Department of Pharmacology (L.L.H.), Emory University, Atlanta, Georgia

Preclinical studies have documented that serotonin (5-HT) can modulate the behavioral effects of cocaine. The present study examined the ability of 5-HT to attenuate the reinforcing and neurochemical effects of cocaine in nonhuman primates. In squirrel monkeys trained to self-administer cocaine (0.1 and 0.3 mg/injection) under a second-order schedule of i.v. drug delivery, the 5-HT uptake inhibitor alaproclate (3.0 and 10.0 mg/kg) and the 5-HT direct agonist quipazine (0.3-1.0 mg/kg) decreased response rates at doses that had no significant effect on behavior maintained by an identical schedule of stimulus termination. The neurochemical bases of the observed drug interactions on behavior were investigated further using in vivo microdialysis techniques in a separate group of awake monkeys to monitor drug-induced changes in extracellular dopamine (DA). Cocaine (1.0 mg/kg) elevated the concentration of DA in the caudate nucleus to approximately 300% of basal levels. Pretreatment with alaproclate or quipazine attenuated cocaine-induced increases in extracellular DA at the same pretreatment doses that decreased cocaine self-administration. The results obtained suggest that increasing brain 5-HT activity can attenuate the reinforcing effects of cocaine, ostensibly by decreasing the ability of cocaine to elevate extracellular DA in brain areas that mediate the behavioral effects. These findings extend those reported previously for the behavioral-stimulant effects of cocaine and identify a potential neurochemical mechanism underlying drug interactions on behavior.

1 Current address: Dr. Paul W. Czoty, Alcohol and Drug Abuse Research Center, Harvard Medical School, McLean Hospital, 115 Mill Street, Belmont, MA 02178.

0022-3565/02/3003-0831$03.00/0
THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
Copyright © 2002 by The American Society for Pharmacology and Experimental Therapeutics


This article has been cited by other articles:


Home page
 J. Pharmacol. Exp. Ther.Home page
K. L. Nicholson, R. L. Balster, K. Golembiowska, M. Kowalska, J. P. Tizzano, P. Skolnick, and A. S. Basile
Preclinical Evaluation of the Abuse Potential of the Analgesic Bicifadine
J. Pharmacol. Exp. Ther., July 1, 2009; 330(1): 236 - 248.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
S. S. Negus, M. H. Baumann, R. B. Rothman, N. K. Mello, and B. E. Blough
Selective Suppression of Cocaine- versus Food-Maintained Responding by Monoamine Releasers in Rhesus Monkeys: Benzylpiperazine, (+)Phenmetrazine, and 4-Benzylpiperidine
J. Pharmacol. Exp. Ther., April 1, 2009; 329(1): 272 - 281.
[Abstract] [Full Text] [PDF]

Home page
 Phil Trans R Soc BHome page
M. A Nader, P. W Czoty, R. W Gould, and N. V Riddick
Positron emission tomography imaging studies of dopamine receptors in primate models of addiction
Phil Trans R Soc B, October 12, 2008; 363(1507): 3223 - 3232.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
S. S. Negus, N. K. Mello, B. E. Blough, M. H. Baumann, and R. B. Rothman
Monoamine Releasers with Varying Selectivity for Dopamine/Norepinephrine versus Serotonin Release as Candidate "Agonist" Medications for Cocaine Dependence: Studies in Assays of Cocaine Discrimination and Cocaine Self-Administration in Rhesus Monkeys
J. Pharmacol. Exp. Ther., February 1, 2007; 320(2): 627 - 636.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
L. L. Howell, F. I. Carroll, J. R. Votaw, M. M. Goodman, and H. L. Kimmel
Effects of Combined Dopamine and Serotonin Transporter Inhibitors on Cocaine Self-Administration in Rhesus Monkeys
J. Pharmacol. Exp. Ther., February 1, 2007; 320(2): 757 - 765.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
R. B. Rothman, B. E. Blough, W. L. Woolverton, K. G. Anderson, S. S. Negus, N. K. Mello, B. L. Roth, and M. H. Baumann
Development of a Rationally Designed, Low Abuse Potential, Biogenic Amine Releaser That Suppresses Cocaine Self-Administration
J. Pharmacol. Exp. Ther., June 1, 2005; 313(3): 1361 - 1369.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
S. Wee, K. G. Anderson, M. H. Baumann, R. B. Rothman, B. E. Blough, and W. L. Woolverton
Relationship between the Serotonergic Activity and Reinforcing Effects of a Series of Amphetamine Analogs
J. Pharmacol. Exp. Ther., May 1, 2005; 313(2): 848 - 854.
[Abstract] [Full Text] [PDF]

Home page
 GeneticsHome page
C. M. Dempsey, S. M. Mackenzie, A. Gargus, G. Blanco, and J. Y. Sze
Serotonin (5HT), Fluoxetine, Imipramine and Dopamine Target Distinct 5HT Receptor Signaling to Modulate Caenorhabditis elegans Egg-Laying Behavior
Genetics, March 1, 2005; 169(3): 1425 - 1436.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
J. K. Rowlett, D. M. Platt, and R. D. Spealman
Cocaine-Like Discriminative Stimulus Effects of Heroin: Modulation by Selective Monoamine Transport Inhibitors
J. Pharmacol. Exp. Ther., July 1, 2004; 310(1): 342 - 348.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
K. P. Lindsey, K. M. Wilcox, J. R. Votaw, M. M. Goodman, C. Plisson, F. I. Carroll, K. C. Rice, and L. L. Howell
Effects of Dopamine Transporter Inhibitors on Cocaine Self-Administration in Rhesus Monkeys: Relationship to Transporter Occupancy Determined by Positron Emission Tomography Neuroimaging
J. Pharmacol. Exp. Ther., June 1, 2004; 309(3): 959 - 969.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
Y. Mateo, E. A. Budygin, C. E. John, and S. R. Jones
Role of serotonin in cocaine effects in mice with reduced dopamine transporter function
PNAS, January 6, 2004; 101(1): 372 - 377.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
M. Gasior, C. A. Paronis, and J. Bergman
Modification by Dopaminergic Drugs of Choice Behavior under Concurrent Schedules of Intravenous Saline and Food Delivery in Monkeys
J. Pharmacol. Exp. Ther., January 1, 2004; 308(1): 249 - 259.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
J. A. Lile, Z. Wang, W. L. Woolverton, J. E. France, T. C. Gregg, H. M. L. Davies, and M. A. Nader
The Reinforcing Efficacy of Psychostimulants in Rhesus Monkeys: The Role of Pharmacokinetics and Pharmacodynamics
J. Pharmacol. Exp. Ther., October 1, 2003; 307(1): 356 - 366.
[Abstract] [Full Text] [PDF]


Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
All ASPET Journals Molecular Pharmacology Pharmacological Reviews
Molecular Interventions Drug Metabolism and Disposition

Copyright © 2002 by the American Society for Pharmacology and Experimental Therapeutics.