JPET Celsis microsomes equal better data

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 Grottick, A. J.
Right arrow Articles by Higgins, G. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Grottick, A. J.
Right arrow Articles by Higgins, G. A.
Right arrowPubmed/NCBI databases
*Compound via MeSH
*Substance via MeSH
Hazardous Substances DB
*COCAINE

Vol. 295, Issue 3, 1183-1191, December 2000

Studies to Investigate the Role of 5-HT2C Receptors on Cocaine- and Food-Maintained Behavior1

Andrew J. Grottick, Paul J. Fletcher2 and Guy A. Higgins

PRBN-B, Pharmaceutical Division, F. Hoffmann-La Roche Ltd., Basel, Switzerland (A.J.G., G.A.H.); and Section of Biopsychology, Centre for Addiction and Mental Health, Clarke Division, Toronto, Ontario, Canada (P.J.F.)

The present series of studies were designed to investigate the 5-HT2C receptor agonist Ro 60-0175 on cocaine- and food-maintained behavior in the rat. Ro 60-0175 (0.1-3 mg/kg, s.c.) reduced cocaine (15 mg/kg, i.p.)-induced hyperactivity. This inhibitory effect of Ro 60-0175 (1 mg/kg, s.c.) was completely blocked by pretreatment with the selective 5-HT2C antagonist SB 242,084 (0.5 mg/kg, i.p.). In further studies, Ro 60-0175 (1-3 mg/kg, s.c.) reduced responding for both food (45-mg Noyes pellet) and cocaine (0.25 mg/infusion) maintained under identical schedules of reinforcement (fixed ratio (5), time out 1 min, 60-min duration). The effect on food-maintained responding was blocked by SB 242,084 (0.5 mg/kg, i.p.). Ro 60-0175 (0.3-3 mg/kg, s.c.) also reduced the breakpoint for cocaine self-administration under a progressive ratio schedule of reinforcement. After a period of extinction training, where cocaine solution was substituted with saline, an acute priming injection of cocaine (15 mg/kg, i.p.) but not Ro 60-0175 (1 mg/kg, s.c.) reinstated cocaine responding. In this model of relapse, Ro 60-0175 (1-3 mg/kg, s.c.) pretreatment attenuated the priming effect of acute cocaine injection. In a final series of studies to examine the cataleptogenic properties of Ro 60-0175, very mild indices of catalepsy were observed at the 3 mg/kg dose only. These catalepsy scores were significantly lower than that produced by haloperidol (0.5 mg/kg, s.c.). In further tests of motor function using the Rotarod, deficits were again seen at the 3 mg/kg dose, but not at lower doses. Taken together, these studies suggest that, in addition to reducing food intake, 5-HT2C receptor agonists reduce cocaine-reinforced behavior. This would be consistent with electrophysiological and biochemical evidence suggesting an important modulatory influence of 5-HT2C receptor activation on mesolimbic dopamine function.

1 Funding for this work was provided by F. Hoffman-La Roche AG.

2 Paul Fletcher is a Career Scientist of the Ontario Ministry of Health. The work conducted in his laboratory was supported by an operating grant from the Medical Research Council of Canada.

0022-3565/00/2953-1183$03.00/0
THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
Copyright © 2000 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
S. J. Ward, T. W. Lefever, C. Jackson, R. J. Tallarida, and E. A. Walker
Effects of a Cannabinoid1 Receptor Antagonist and Serotonin2C Receptor Agonist Alone and in Combination on Motivation for Palatable Food: A Dose-Addition Analysis Study in Mice
J. Pharmacol. Exp. Ther., May 1, 2008; 325(2): 567 - 576.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
M. Pierucci, V. Di Matteo, and E. Esposito
Stimulation of Serotonin2C Receptors Blocks the Hyperactivation of Midbrain Dopamine Neurons Induced by Nicotine Administration
J. Pharmacol. Exp. Ther., April 1, 2004; 309(1): 109 - 118.
[Abstract] [Full Text]

Home page
 J. Neurosci.Home page
P. De Deurwaerdere, S. Navailles, K. A Berg, W. P. Clarke, and U. Spampinato
Constitutive Activity of the Serotonin2C Receptor Inhibits In Vivo Dopamine Release in the Rat Striatum and Nucleus Accumbens
J. Neurosci., March 31, 2004; 24(13): 3235 - 3241.
[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
M. Filip and K. A. Cunningham
Hyperlocomotive and Discriminative Stimulus Effects of Cocaine Are Under the Control of Serotonin2C (5-HT2C) Receptors in Rat Prefrontal Cortex
J. Pharmacol. Exp. Ther., August 1, 2003; 306(2): 734 - 743.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
B. A. Rocha, E. H. Goulding, L. E. O'Dell, A. N. Mead, N. G. Coufal, L. H. Parsons, and L. H. Tecott
Enhanced Locomotor, Reinforcing, and Neurochemical Effects of Cocaine in Serotonin 5-Hydroxytryptamine 2C Receptor Mutant Mice
J. Neurosci., November 15, 2002; 22(22): 10039 - 10045.
[Abstract] [Full Text] [PDF]

Home page
 Pharmacol. Rev.Home page
U. Shalev, J. W. Grimm, and Y. Shaham
Neurobiology of Relapse to Heroin and Cocaine Seeking: A Review
Pharmacol. Rev., March 1, 2002; 54(1): 1 - 42.
[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 © 2000 by the American Society for Pharmacology and Experimental Therapeutics.