Acquisition of and withdrawal from cocaine self-administration regulates 5-HT mRNA expression in rat striatum.

Full Abstract

This study investigated how different stages of cocaine self-administration in rats affect the expression of two serotonin receptors in dorsal and ventral striatum, the 5-HT(1B) and 5-HT(6) subtypes, which have both been implicated in mediating some aspects of cocaine-related behaviors. In the first experiment, rats were trained to work for saccharin (oral) or cocaine (i.v.) reinforcers. We found that continuous access to cocaine for 23 days did not change the level of 5-HT(1B) mRNA expression compared to control animals receiving saccharin. However, a single cocaine session, given either by self-administration or non-contingently, increased 5-HT(1B) mRNA in dorsal striatum, whereas forced abstinence for two weeks after cocaine reduced 5-HT(1B) mRNA expression in the same subregion. 5-HT(6) mRNA was not changed by any of these treatments. A follow-up experiment investigated the effects of limited versus extended access to cocaine as well as forced abstinence, and we found that 14 days of forced abstinence significantly reduced 5-HT(1B) mRNA throughout the dorsal and ventral striatum compared to no withdrawal. These results suggest that the influence of 5-HT(1B) receptors in striatal projection neurons may be increased during cocaine acquisition and reduced after forced abstinence and may therefore be targets for pharmacological intervention in addiction.

Author information

Author/s: Neumaier, John F (JF); McDevitt, Ross A (RA); Polis, Ilham Y (IY); Parsons, Loren H (LH);

Affiliation: Department of Psychiatry and Behavioral Sciences, Harborview Medical Center, Seattle, Washington, USA. neumaier(-atsign-)u.washington.edu

Grants: AA12294 (Agency:NIAAA NIH HHS) ; DA024194 (Agency:NIDA NIH HHS) ; DA16432 (Agency:NIDA NIH HHS) ; GM07108 (Agency:NIGMS NIH HHS)

Journal and publication information

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

Journal: Journal of neurochemistry (J Neurochem), published in England. (Language: eng)

Reference: 2009-Oct; vol 111 (issue 1) : pp 217-27

Dates: Created 2009/09/23; Completed 2009/10/09;

PMID: 19659573, status: MEDLINE (last retrieval date: 10/9/2009, IMS Date: )

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.

Animals
Behavior, Animal - drug effects
Cocaine - administration & dosage; pharmacology
Conditioning, Operant - drug effects
Corpus Striatum - drug effects; metabolism
Dopamine Uptake Inhibitors - administration & dosage; pharmacology
Gene Expression Regulation - drug effects
Male

Male
RNA, Messenger - metabolism
Rats
Rats, Wistar
Receptor, Serotonin, 5-HT1B - genetics; metabolism
Self Administration
Serotonin - genetics; metabolism
Substance Withdrawal Syndrome - pathology

Associated Chemicals: Dopamine Uptake Inhibitors (0) ; RNA, Messenger (0) ; Receptor, Serotonin, 5-HT1B (0) ; Cocaine (50-36-2) ; Serotonin (50-67-9)

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