Spatial and temporal profile of haloperidol-induced immediate-early gene expression and phosphoCREB binding in the dorsal and ventral striatum of amphetamine-sensitized rats.
To determine if D(2) dopamine receptor-mediated nuclear signaling is altered during the development of amphetamine sensitization, we examined the expression of immediate-early gene (IEG) products, Fos, Jun, and Fos-related antigen (FRA), in both controls and amphetamine-sensitized rats after a challenge with the D(2) antagonist haloperidol. When chronic saline- or amphetamine (5 mg/kg, i.p. for 14 days)-treated rats were challenged with 2 mg/kg haloperidol at withdrawal day 3 (w3), more 35-kDa FRA was induced in the ventral striatum of the control group than in the amphetamine-treated rats. In contrast, more Jun and 35-kDa FRA were expressed in the ventral striatum of the amphetamine-treated group than in the controls when haloperidol was given at w10. Topographical analyses indicate that the decrease in FRA immunoreactive neuronal density in amphetamine-treated rats at w3 were located in the dorsolateral caudate/putamen and the nucleus accumbens shell and core subregions. Conversely, the increase in Jun-immunoreactive neurons in amphetamine-treated rats at w10 was observed in the dorsolateral caudate/putamen; in the case of the FRAs, the increase was observed in the nucleus accumbens shell. In addition, the time-dependent profile of IEG expression paralleled the activation of an upstream regulator, cAMP-response element binding protein, in the ventral striatum after haloperidol treatment. These neurochemical changes may be associated with behavioral plasticity, since amphetamine-treated rats displayed a lower amount of locomotor activity when exposed to a novel environment at w3, but had recovered at w10. Overall, the current study reveals that there is a distinct temporal and spatial profile of haloperidol-induced IEG expression and/or CREB phosphorylation in amphetamine-treated rats, suggesting that there is a critical transition between the early and late withdrawal periods.
Hsieh
Huei-Ching
HC
Department of Pharmacology, School of Medicine, Chang-Gung University, 259 Wen-Hwa 1st Road, Tao-Yuan, Kwei-Shan, Taiwan, R.O.C. 333.
Li
Hui-Yun
HY
Lin
Ming-Yu
MY
Chiou
Ya-Fen
YF
Lin
Shao-Yun
SY
Wong
Chung-Hung
CH
Chen
Jin-Chung
JC
D000661:Amphetamine / Q000494:pharmacology*; D019969:Amphetamine-Related Disorders / Q000503:physiopathology; D000818:Animals; D001479:Basal Ganglia / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D018492:Dopamine Antagonists / Q000494:pharmacology*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D017781:Genes, Immediate-Early / Q000187:drug effects; D006220:Haloperidol / Q000494:pharmacology*; D007150:Immunohistochemistry; D008297:Male; D009473:Neuronal Plasticity / Q000187:drug effects; D010766:Phosphorylation; D016760:Proto-Oncogene Proteins c-fos / Q000032:analysis / Q000235:genetics; D016755:Proto-Oncogene Proteins c-jun / Q000032:analysis / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D017448:Receptors, Dopamine D2 / Q000032:analysis / Q000378:metabolism; D012965:Sodium Chloride / Q000494:pharmacology; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology; D018808:Transcription Factor AP-1 / Q000378:metabolism
D017362:Cyclic AMP Response Element-Binding Protein; D018492:Dopamine Antagonists; D018765:Dopamine Uptake Inhibitors; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; D017448:Receptors, Dopamine D2; D018808:Transcription Factor AP-1; D012965:Sodium Chloride; D000661:Amphetamine; D006220:Haloperidol