Modulation of a (+)amphetamine discriminative stimulus in rats by 8-hydroxy-2-(N,N-di-n-propylamino)tetralin (8-OH DPAT).

Full Abstract

It is well established that the discriminative stimulus (DS) effect of amphetamine involves a dopaminergic and/or noradrenergic mechanism. These catecholamines can be modulated by the 5-HT(1A) serotonin receptor agonist 8-hydroxy-2-(N,N-di-n-propylamino)tetralin (8-OH DPAT). The present study was conducted to determine whether 8-OH DPAT could influence the DS effects of (+)amphetamine. Administration of 8-OH DPAT doses to Sprague-Dawley rats trained to discriminate 1 mg/kg of (+)amphetamine (ED(50)=0.33 mg/kg) using a two-lever operant paradigm (VI-15 s schedule of reinforcement for appetitive reward) failed to result in stimulus generalization when administered alone, and failed to antagonize the stimulus effect when administered in combination with the training dose of (+)amphetamine. However, administration of 8-OH DPAT doses that produced saline-like responding (i.e., 0.01-0.1 mg/kg; <20% amphetamine-appropriate responding) in combination with the ED(50) dose of (+)amphetamine resulted in the animals' making a progressively greater number of responses on the drug-appropriate lever such that a combination of 0.1 mg/kg of 8-OH DPAT plus (+)amphetamine (0.33 mg/kg) elicited 91% (+)amphetamine-appropriate responding. In a separate study, administration of (+)amphetamine doses in combination with fixed doses of 8-OH DPAT (either 0.01 or 0.1 mg/kg) resulted in an apparent leftward shift of the dose-response curve. The results indicate that (+)amphetamine can be more effective as a discriminative stimulus in the presence of 8-OH DPAT than in its absence.

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Author information

Author/s: Young, Richard (R); Bondareva, Tatiana (T); Wesolowska, Anna (A); Glennon, Richard A (RA);

Affiliation: Department of Medicinal Chemistry, School of Pharmacy, Medical College of Virginia, Box 980540, Virginia Commonwealth University, Richmond, 23298-0540, USA.

Grants: DA 01642 (Agency:NIDA NIH HHS)

Journal and publication information

Publication Type: Journal Article; Research Support, N.I.H., Extramural

Journal: Pharmacology, biochemistry, and behavior (Pharmacol Biochem Behav), published in United States. (Language: eng)

Reference: 2006-Apr; vol 83 (issue 4) : pp 612-7

Dates: Created 2006/06/09; Completed 2006/08/16; Revised 2007/11/14;

PMID: 16675002, status: MEDLINE (last retrieval date: 12/26/2008)

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

8-Hydroxy-2-(di-n-propylamino)tetralin - pharmacology
Amphetamine - pharmacology
Animals
Discrimination Learning - drug effects
Dose-Response Relationship, Drug
Male

Male
Rats
Rats, Sprague-Dawley
Receptor, Serotonin, 5-HT1A - physiology
Receptors, Serotonin - physiology
Serotonin Agonists - pharmacology

Associated Chemicals: Receptors, Serotonin (0) ; Serotonin Agonists (0) ; serotonin 7 receptor (0) ; Receptor, Serotonin, 5-HT1A (112692-38-3) ; Amphetamine (300-62-9) ; 8-Hydroxy-2-(di-n-propylamino)tetralin (78950-78-4)

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