title: Amphetamine-evoked c-fos mRNA expression in the caudate-putamen: the effects of DA and NMDA receptor antagonists vary as a function of neuronal phenotype and environmental context.
abstract: Dopamine (DA) and glutamate neurotransmission is thought to be critical for psychostimulant drugs to induce immediate early genes (IEGs) in the caudate-putamen (CPu). We report here, however, that the ability of DA and glutamate NMDA receptor antagonists to attenuate amphetamine-evoked c-fos mRNA expression in the CPu depends on environmental context. When given in the home cage, amphetamine induced c-fos mRNA expression predominately in preprodynorphin and preprotachykinin mRNA-containing neurons (Dyn-SP+ cells) in the CPu. In this condition, all of the D1R, D2R and NMDAR antagonists tested dose-dependently decreased c-fos expression in Dyn-SP+ cells. When given in a novel environment, amphetamine induced c-fos mRNA in both Dyn-SP+ and preproenkephalin mRNA-containing neurons (Enk+ cells). In this condition, D1R and non-selective NMDAR antagonists dose-dependently decreased c-fos expression in Dyn-SP+ cells, but neither D2R nor NR2B-selective NMDAR antagonists had no effect. Furthermore, amphetamine-evoked c-fos expression in Enk+ cells was most sensitive to DAR and NMDAR antagonism; the lowest dose of every antagonist tested significantly decreased c-fos expression only in these cells. Finally, novelty-stress also induced c-fos expression in both Dyn-SP+ and Enk+ cells, and this was relatively resistant to all but D1R antagonists. We suggest that the mechanism(s) by which amphetamine evokes c-fos expression in the CPu varies depending on the stimulus (amphetamine vs. stress), the striatal cell population engaged (Dyn-SP+ vs. Enk+ cells), and environmental context (home vs. novel cage).
authors.affiliation: Neuroscience Program, University of Michigan, Ann Arbor 48109, USA.
authors.forename: Susan M
authors.initials: SM
authors.lastname: Ferguson
authors.forename: Camille S
authors.initials: CS
authors.lastname: Norton
authors.forename: Stanley J
authors.initials: SJ
authors.lastname: Watson
authors.forename: Huda
authors.initials: H
authors.lastname: Akil
authors.forename: Terry E
authors.initials: TE
authors.lastname: Robinson
mesh_terms: D000661:Amphetamine / Q000494:pharmacology*; D000818:Animals; D002421:Caudate Nucleus / Q000187:drug effects / Q000378:metabolism*; D002452:Cell Count; D018492:Dopamine Antagonists / Q000494:pharmacology; D065127:Dopamine D2 Receptor Antagonists; D004305:Dose-Response Relationship, Drug; D004399:Dynorphins / Q000235:genetics; D004777:Environment; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D017403:In Situ Hybridization; D008297:Male; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010641:Phenotype; D011498:Protein Precursors / Q000235:genetics; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics*; D011699:Putamen / Q000187:drug effects / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D013037:Spatial Behavior / Q000502:physiology; D015320:Tachykinins / Q000235:genetics
chemical_list: D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; D018691:Excitatory Amino Acid Antagonists; D011498:Protein Precursors; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D017447:Receptors, Dopamine D1; D016194:Receptors, N-Methyl-D-Aspartate; D015320:Tachykinins; C036448:pre-prodynorphin; C044206:preprotachykinin; D004399:Dynorphins; D000661:Amphetamine