title: Differential effects of D1 and D2 dopamine receptor antagonists on acute amphetamine- or methamphetamine-induced up-regulation of zif/268 mRNA expression in rat forebrain.
abstract: This study investigated the hypothesis that D1 and D2 dopamine receptors interact to regulate the expression of zif/268 mRNA in rat forebrain after an acute injection of amphetamine or methamphetamine. Forty-five minutes and 3 h after a single injection of amphetamine (4 mg/kg i.p.) or methamphetamine (4 mg/kg i.p.), the mRNA expression of zif/268 in dorsal striatum and sensorimotor cortex was increased, as revealed by quantitative in situ hybridization histochemistry. Induction was more intense in striatal patches at 45 min than at 3 h, when a more homogeneous pattern of zif/268 mRNA induction was observed. SCH 23390, a selective D1 receptor antagonist, suppressed, and eticlopride, a D2 receptor antagonist, elevated, constitutive zif/268 mRNA levels in the striatum, but neither antagonist had a significant effect on the constitutive expression of zif/268 in soensorimotor cortex. Pretreatment with SCH 23390 completely blocked the stimulant-induced zif/268 expression in striatum and partially blocked the stimulant-induced zif/268 expression in cortex. Pretreatment with eticlopride augmented zif/268 mRNA expression in patch and matrix compartments of dorsal and ventral striatum 45 min after amphetamine or methamphetamine injection. However, at 3 h, eticloprides completely blocked amphetamine- and methamphetamine-stimulated zif/268 mRNA in dorsomedial, but not dorsolateral, striatum. In addition, eticlopride partially blocked cortical zif/268 induction by both amphetamines. Both antagonists prevented stimulant-induced hyperlocomotion and stereotypies. These results demonstrate that D1 and D2 receptors in mesolimbic/mesostriatal pathways both regulate amphetamine- and methamphetamine-stimulated behaviors and zif/268 mRNA expression. Furthermore, the effect of D2 receptor blockade on zif/268 expression was found to be contingent on the time interval investigated after psychostimulant administration.
authors.affiliation: Department of Anatomy and Cell Biology, East Carolina University School of Medicine, Greenville, North Carolina, USA.
authors.forename: J Q
authors.initials: JQ
authors.lastname: Wang
authors.forename: J F
authors.initials: JF
authors.lastname: McGinty
mesh_terms: D000661:Amphetamine / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001552:Benzazepines / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000235:genetics*; D018492:Dopamine Antagonists / Q000494:pharmacology*; D065127:Dopamine D2 Receptor Antagonists; D051766:Early Growth Response Protein 1; D017874:Immediate-Early Proteins; D008297:Male; D008694:Methamphetamine / Q000494:pharmacology*; D016548:Prosencephalon / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors; D012457:Salicylamides / Q000494:pharmacology; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D001552:Benzazepines; D004268:DNA-Binding Proteins; D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; D051766:Early Growth Response Protein 1; C486110:Egr1 protein, rat; D017874:Immediate-Early Proteins; D012333:RNA, Messenger; D017447:Receptors, Dopamine D1; D012457:Salicylamides; D014157:Transcription Factors; D008694:Methamphetamine; D000661:Amphetamine; C045989:eticlopride