title: Temporal and anatomic patterns of immediate-early gene expression in the forebrain of C57BL/6 and DBA/2 mice after morphine administration.
abstract: Although morphine was previously reported to produce an instant induction of c-fos in the striatum, our recent studies have demonstrated that the expression of numerous immediate early genes (IEGs) is significantly elevated at delayed time-points (several hours) after morphine administration. To better dissect the time-course of opioid-produced IEG induction, we used in situ hybridization to examine the expression of the IEGs c-fos, zif268 and arc in the mouse forebrain at several time-points after acute morphine injection. To link drug-produced behavioral changes with the activity of specific neuronal complexes, this study was performed comparatively in the C57BL/6 and DBA/2 mouse strains, which differ markedly in their locomotor responses to opioids and opioid reward. Our study demonstrates that morphine produces two episodes of IEG induction, which are separate in time (30 min vs. 4-6 h) and which have different neuroanatomic distribution. At 30 min, one or more IEGs were induced in circumscribed subregions of the dorsal striatum (dStr) and of the nucleus accumbens (NAc) shell, as well as in the lateral septum. The observed inter-strain differences in IEG expression at 30 min support earlier proposals that activation of the dorsomedial striatum may mediate morphine-elicited locomotor stimulation (both effects were present only in the C57BL/6 strain). In contrast, NAc shell activation does not appear to be linked to morphine-elicited changes in locomotor behavior. The second IEG induction (of arc and of zif268) was more widespread, involving most of the dStr and the cortex. The second IEG induction peaked earlier in the DBA/2 mice than in the C57BL/6 mice (4 h compared with 6 h) and displayed no apparent relation to locomotor behavior. This delayed episode of IEG activation, which has largely been overlooked thus far, may contribute to the development of long-term effects of opioids such as tolerance, dependence and/or addiction.
authors.affiliation: Department of Molecular Neuropharmacology, Institute of Pharmacology, Polish Academy of Sciences, Smętna 12, 31-343 Kraków, Poland. Electronic address: nfziolko@cyf-kr.edu.pl.
authors.forename: B
authors.initials: B
authors.lastname: ZióŁkowska
authors.affiliation: Department of Molecular Neuropharmacology, Institute of Pharmacology, Polish Academy of Sciences, Smętna 12, 31-343 Kraków, Poland.
authors.forename: A
authors.initials: A
authors.lastname: Gieryk
authors.affiliation: Department of Molecular Neuropharmacology, Institute of Pharmacology, Polish Academy of Sciences, Smętna 12, 31-343 Kraków, Poland; Department of Neurobiology and Neuropsychology, Institute of Applied Psychology, Jagiellonian University, Łojasiewicza 4, 30-348 Kraków, Poland.
authors.forename: W
authors.initials: W
authors.lastname: Solecki
authors.affiliation: Department of Molecular Neuropharmacology, Institute of Pharmacology, Polish Academy of Sciences, Smętna 12, 31-343 Kraków, Poland; Department of Neurobiology and Neuropsychology, Institute of Applied Psychology, Jagiellonian University, Łojasiewicza 4, 30-348 Kraków, Poland.
authors.forename: R
authors.initials: R
authors.lastname: PrzewŁocki
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001931:Brain Mapping; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism; D051766:Early Growth Response Protein 1 / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects*; D017874:Immediate-Early Proteins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D009020:Morphine / Q000008:administration & dosage*; D009043:Motor Activity / Q000187:drug effects; D009294:Narcotics / Q000008:administration & dosage*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D016548:Prosencephalon / Q000033:anatomy & histology* / Q000187:drug effects*; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism; D013045:Species Specificity; D013997:Time Factors
chemical_list: D003598:Cytoskeletal Proteins; D051766:Early Growth Response Protein 1; C486109:Egr1 protein, mouse; D017874:Immediate-Early Proteins; D009294:Narcotics; D009419:Nerve Tissue Proteins; D016760:Proto-Oncogene Proteins c-fos; C092069:activity regulated cytoskeletal-associated protein; D009020:Morphine
keywords: immediate early gene; inbred strain; morphine; opioid; striatum