JPET

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


     

Journal of Pharmacology And Experimental Therapeutics Fast Forward
First published on January 26, 2005; DOI: 10.1124/jpet.104.080101

This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
jpet.104.080101v1
313/2/848    most recent
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
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 Wee, S.
Right arrow Articles by Woolverton, W. L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Wee, S.
Right arrow Articles by Woolverton, W. L.


Received for publication November 8, 2004.
Revised January 10, 2005.
Accepted for publication January 25, 2005.

Relationship between the serotonergic activity and reinforcing effects of a series of amphetamine analogs

Sunmee Wee 1, Karen G. Anderson 2, Michael H. Baumann 3, Richard B. Rothman 3, Bruce E. Blough 4, William L. Woolverton 1*

1 University of Mississippi Medical Center 2 West Virginia University 3 National Institute on Drug Abuse 4 Research Triangle Institute International

* Address correspondence to: E-mail: wwoolverton{at}psychiatry.umsmed.edu

Abstract

It has been reported that among drugs with mixed actions on CNS monoamine systems, increased serotonergic activity is associated with decreased potency as a reinforcer. The present experiment was designed to examine this relationship for amphetamine analogs that varied in serotonin releasing potency, and to evaluate the possibility that serotonergic actions can affect reinforcing efficacy. Compounds PAL 313 and 314 are para- and meta-methylamphetamine, respectively. PAL 303 and 353 are para- and meta-fluoroamphetamine, respectively. All compounds had similar potencies as in vitro releasers of DA and NE but differed in potency for 5-HT release [EC50 (nM) PAL 313=53.4; PAL 314=218; PAL 303=939; PAL 353=1937]. When made available to rhesus monkeys (N=4) for self- administration under a fixed-ratio 25 schedule, all were positive reinforcers with biphasic dose-response functions (0.003 - 1.0 mg/kg), and were equipotent. PAL 313 was self-administered at a lower rate than the other compounds, which were indistinguishable. Under a progressive-ratio schedule (N=5), all drugs were positive reinforcers. Dose-response functions increased to a maximum or were biphasic (0.01 - 1.0 mg/kg), and drugs were equipotent. At maximum, PAL 313 maintained less responding than other PAL drugs, which maintained similar maxima. Thus, all compounds were positive reinforcers under both schedules, consistent with their potent DA actions. Responding was lower when 5-HT potency was higher and comparable to DA and NE potency. The results suggest that the mechanism for this effect involves a decrease in reinforcing efficacy among monoamine releasing agents when 5-HT releasing potency is increased relative to DA.


Key words: dopamine, psychostimulants, reinforcing efficacy, rhesus monkeys, self-administration, serotonin


This article has been cited by other articles:


Home page
 J. Pharmacol. Exp. Ther.Home page
Y. Liang, A. M. Shaw, M. Boules, S. Briody, J. Robinson, A. Oliveros, E. Blazar, K. Williams, Y. Zhang, P. R. Carlier, et al.
Antidepressant-Like Pharmacological Profile of a Novel Triple Reuptake Inhibitor, (1S,2S)-3-(Methylamino)-2-(naphthalen-2-yl)-1-phenylpropan-1-ol (PRC200-SS)
J. Pharmacol. Exp. Ther., November 1, 2008; 327(2): 573 - 583.
[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 Help [Feedback] [For Subscribers] [Archive] [Search] --
All ASPET Journals Molecular Pharmacology Pharmacological Reviews
Molecular Interventions Drug Metabolism and Disposition

Copyright © 2005 by the American Society for Pharmacology and Experimental Therapeutics.