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PMID: 10407052 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Addiction-prone Lewis but not Fischer rats develop compulsive running that coincides with downregulation of nerve growth factor inducible-B and neuron-derived orphan receptor 1.

The Journal of neuroscience : the official journal of the Society for Neuroscience ·Vol. 19 ·No. 14 ·1999-07-15 ·Pages 6169-74

Werme M, Thorén P, Olson L, Brené S

Abstract

We have examined the effects of chronic voluntary running for 30 d on the levels of nerve growth factor inducilble-B (NGFI-B) and neuron-derived orphan receptor 1 (NOR1) mRNAs in Fischer and Lewis rats. The aim was to compare the addiction-prone Lewis rat strain to the Fischer strain in a plausible model for natural reward. The Lewis strain ran markedly more than the Fischer strain, as indicated by the length of running per day when given free access to running wheels. Both strains progressively increased their amount of daily running. By day 14, Lewis rats had reached a maximal level corresponding to 10 km/d, which slowly decreased to approximately 8 km/d. Fischer rats ran considerably less, averaging approximately 1. 5 km/d by day 30. After 30 d of running, levels of mRNA encoding NGFI-B and Nor1 were decreased in cerebral cortex in Lewis but not Fischer rats. The downregulation of NGFI-B mRNA in Lewis rats could not be attenuated by the opioid receptor antagonist naloxone. Instead, naloxone by itself downregulated NGFI-B in striatum and cerebral cortex in both strains. In contrast, naloxone had no effect on Nor1 mRNA levels, although the running-induced downregulation of Nor1 was, in most cases, attenuated by naloxone. Data from the present study suggest that the same genetic factors contributing to the drug addiction-prone behavior of Lewis rats also control the excessive running behavior and that this coincides with downregulation of transcription factors of the NGFI-B family.

MeSH Terms
Animals Brain/metabolism DNA-Binding Proteins/genetics Down-Regulation Gene Expression Regulation In Situ Hybridization Motor Activity Nerve Tissue Proteins/genetics Nuclear Receptor Subfamily 4, Group A, Member 1 Nuclear Receptor Subfamily 4, Group A, Member 2 RNA, Messenger/genetics Rats Rats, Inbred F344 Rats, Inbred Lew Receptors, Cytoplasmic and Nuclear Receptors, Steroid/genetics Species Specificity Substance-Related Disorders/genetics,physiopathology Transcription Factors/genetics Transcription, Genetic
Chemicals
DNA-Binding Proteins Nerve Tissue Proteins Nr4a1 protein, rat Nr4a2 protein, rat Nr4a3 protein, rat Nuclear Receptor Subfamily 4, Group A, Member 1 Nuclear Receptor Subfamily 4, Group A, Member 2 RNA, Messenger Receptors, Cytoplasmic and Nuclear Receptors, Steroid Transcription Factors
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Werme M
Department of Neuroscience, Karolinska Institutet, S-171 77 Stockholm, Sweden.
Thorén P
Olson L
Brené S
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Article Info
Journal
The Journal of neuroscience : the official journal of the Society for Neuroscience
Abbr.
J Neurosci
ISSN
1529-2401
Published
1999-07-15
Pages
6169-74
Language
English
Region
United States
NLM ID
8102140
PMCID
PMC6783058
Subset
IM
External Links
PubMed source PMC Full Text View journal details
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