NGFI-B and nor1 mRNAs are upregulated in brain reward pathways by drugs of abuse: different effects in Fischer and Lewis rats.
The two inbred Fischer and Lewis rat strains display differences in acquisition of drug self-administration, suggesting genetic factors controlling the vulnerability to drugs of abuse. In this study, we analyzed the effects of acute and chronic cocaine and morphine on mRNAs encoding the NGFI-B/Nur77 family of nuclear orphan receptors in reward pathways in Fischer and Lewis rats. After a single injection of cocaine, a similar upregulation of NGFI-B mRNA in striatal subregions and cortex cinguli was seen in both Fischer and Lewis rats. In contrast, Nor1 mRNA was only significantly upregulated by cocaine in the Fischer rats. Morphine increased NGFI-B mRNA in medial caudate putamen and cortex cinguli in Lewis rats and Nor1 mRNA in medial caudate putamen in Fischer rats. Chronic cocaine upregulated NGFI-B mRNA in nucleus accumbens core, lateral caudate putamen and cingulate cortex in Fischer rats, whereas no effect was seen in Lewis rats. In contrast, Nor1 mRNA levels were upregulated in Lewis rats in medial caudate putamen and cingulate cortex after chronic cocaine and in cingulate cortex after chronic morphine. No effect on Nor1 mRNA levels was seen in Fischer rats after chronic treatments. Our results demonstrate different responses in addiction-prone Lewis rats as compared to the less addiction-prone Fischer rats with respect to NGFI-B and Nor1 mRNA regulation after acute and repeated administration of cocaine and morphine. Thus, we suggest that the transcription factors NGFI-B and Nor1 might be involved in the control of behaviors such as sensitized locomotor response, craving and aversion that appears after repeated administration of abused drugs.
Werme
M
M
Department of Neuroscience, Karolinska Institutet, S-171 77, Stockholm, Sweden.
Olson
L
L
Brené
S
S
D000818:Animals; D001921:Brain / Q000033:anatomy & histology / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D003042:Cocaine / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D006179:Gyrus Cinguli / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D009294:Narcotics / Q000494:pharmacology*; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D011917:Rats, Inbred Lew; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid; D012201:Reward; D013045:Species Specificity; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
D004268:DNA-Binding Proteins; D009294:Narcotics; D009419:Nerve Tissue Proteins; C539820:Nr4a1 protein, rat; C091333:Nr4a3 protein, rat; D009687:Nuclear Proteins; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid; D014157:Transcription Factors; D009020:Morphine; D003042:Cocaine