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.
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.
Department of Neuroscience, Karolinska Institutet, S-171 77 Stockholm, Sweden.
M
M
Werme
P
P
Thorén
L
L
Olson
S
S
Brené
D000818:Animals; D001921:Brain / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics*; D015536:Down-Regulation; D005786:Gene Expression Regulation; D017403:In Situ Hybridization; D009043:Motor Activity; D009419:Nerve Tissue Proteins / Q000235:genetics*; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D057126:Nuclear Receptor Subfamily 4, Group A, Member 2; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D011916:Rats, Inbred F344; D011917:Rats, Inbred Lew; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid / Q000235:genetics; D013045:Species Specificity; D019966:Substance-Related Disorders / Q000235:genetics / Q000503:physiopathology; D014157:Transcription Factors / Q000235:genetics*; D014158:Transcription, Genetic
D004268:DNA-Binding Proteins; D009419:Nerve Tissue Proteins; C539820:Nr4a1 protein, rat; C539884:Nr4a2 protein, rat; C091333:Nr4a3 protein, rat; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D057126:Nuclear Receptor Subfamily 4, Group A, Member 2; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid; D014157:Transcription Factors