Research article summary (published 30 Jan 2009):

Reduced sensitivity to the locomotor-stimulant effects of cocaine is associated with increased sensitivity to its discriminative stimulus properties.

Full Abstract

Outbred Long-Evans rats exhibit wide variation in their locomotor response to cocaine. Here, we investigated the relationship between these individual differences and interoceptive effects of cocaine in low cocaine responder (LCR) and high cocaine responder (HCR) phenotypes. Rats were trained to discriminate cocaine (10.0 mg/kg, intraperitoneally) from saline by repeated pairings of injections with one of two response levers. In subsequent tests for stimulus generalization to other cocaine doses (1.25-15.0 mg/kg), LCRs exhibited partial-to-full generalization at 1.85 and 2.5 mg/kg cocaine, respectively, whereas HCRs did not. When the selective 5-HT reuptake inhibitor fluoxetine (5.0 mg/kg) was coadministered with saline or different cocaine doses, we observed similar upward shifts in dose-response in both phenotypes. In contrast, coadministration of the 5-HT2A/2C agonist (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI; 0.3 mg/kg) led to partial substitution of DOI for cocaine and enhancement of the stimulus properties of 1.25 mg/kg cocaine in LCRs only. Finally, a retest of cocaine-induced locomotion after discrimination testing revealed marked behavioral sensitization in LCRs and modest changes in behavior in HCRs. Taken together, these results suggest that initial sensitivity to the locomotor-stimulant effects of cocaine is inversely related to its interoceptive properties and that differences in 5-HT systems may contribute to the phenotypic differences observed.

Author information

Author/s: Klein, David A (DA); Gulley, Joshua M (JM);

Affiliation: Department of Psychology and Neuroscience Program, University of Illinois, Urbana-Champaign, Champaign, Illinois 61820, USA.

Journal and publication information

Publication Type: Journal Article; Research Support, Non-U.S. Gov't

Journal: Behavioural pharmacology (Behav Pharmacol), published in England. (Language: eng)

Reference: 2009-Feb; vol 20 (issue 1) : pp 67-77

Dates: Created 2009/01/30; Completed 2009/03/03; Revised 2009/07/07;

PMID: 19125118, status: MEDLINE (last retrieval date: 7/24/2009, IMS Date: 24 Jul 2009 00:00:00)

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.

Amphetamines - agonists; pharmacology Animals Cocaine - pharmacology Conditioning, Operant - drug effects Discrimination Learning - drug effects Dose-Response Relationship, Drug Drug Combinations Fluoxetine - pharmacology

Generalization, Stimulus - drug effects Motor Activity - drug effects Rats Rats, Long-Evans Receptor, Serotonin, 5-HT2A - agonists Receptor, Serotonin, 5-HT2C - agonists Reinforcement Schedule Serotonin Agonists - pharmacology

Associated Chemicals: Amphetamines (0) ; Drug Combinations (0) ; Receptor, Serotonin, 5-HT2A (0) ; Receptor, Serotonin, 5-HT2C (0) ; Serotonin Agonists (0) ; Cocaine (50-36-2) ; Fluoxetine (54910-89-3) ; 4-iodo-2,5-dimethoxyphenylisopropylamine (64584-34-5)

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