title: Amphetamine-induced zif268 mRNA expression in the medial posterior nucleus accumbens in cholecystokinin-A receptor mutant rats.
abstract: Converging evidence supports a role for cholecystokinin (CCK) in modulating dopamine (DA)-mediated activity in the rat mesolimbic system. In particular, CCK co-localized with mesolimbic DA cells originating in the ventral tegmental area potentiates DA function in the medial posterior nucleus accumbens (mpNA) through CCK-A receptors. Recently, a strain of rats lacking the CCK-A receptor, Otsuka Long Evans Tokushima Fatty (OLETF), has been discovered making it possible to study the mesolimbic DA regulatory role of CCK-A receptors. Previous studies have shown that OLETF rats are less sensitive to amphetamine (AMPH)-induced behavioral effects compared to controls. To determine if this altered sensitivity is associated with decreased AMPH-induced postsynaptic activation in the mpNA in OLETF rats, we performed the following experiment. OLETF (CCK-A mutants) and Long Evans Tokushima Otsuka (LETO) rats (controls) were given subcutaneous injections of either saline or AMPH (5.0 mg/kg). One hour after injection all animals were sacrificed and activation of the mpNA was assessed using in situ hybridization with antisense probes for zif268 mRNA. AMPH treatment produced a significant up-regulation of zif268 mRNA expression in both OLETF and LETO rats (P</=0.0002), compared to saline treatment. However, AMPH had almost an identical effect on zif268 mRNA expression in the mpNA in both rat strains suggesting similar postsynaptic neural activation. The significance of this AMPH-induced zif268 mRNA expression in these two rat strains and its relationship to CCK function in the nucleus accumbens are discussed.
authors.affiliation: Department of Psychiatry, School of Medicine, University of California, San Diego, La Jolla 92103-8620, USA.
authors.forename: P D
authors.initials: PD
authors.lastname: Shilling
authors.forename: D
authors.initials: D
authors.lastname: Feifel
authors.forename: J R
authors.initials: JR
authors.lastname: Kelsoe
mesh_terms: D000661:Amphetamine / Q000494:pharmacology*; D000818:Animals; D004268:DNA-Binding Proteins / Q000235:genetics*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D051766:Early Growth Response Protein 1; D005786:Gene Expression Regulation / Q000187:drug effects; D017874:Immediate-Early Proteins; D017403:In Situ Hybridization; D007279:Injections, Subcutaneous; D009154:Mutation; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics*; D051381:Rats; D020334:Rats, Inbred OLETF; D020318:Rats, Long-Evans; D043886:Receptor, Cholecystokinin A; D011949:Receptors, Cholecystokinin / Q000235:genetics* / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics*; D015854:Up-Regulation
chemical_list: D004268:DNA-Binding Proteins; D018765:Dopamine Uptake Inhibitors; D051766:Early Growth Response Protein 1; C486110:Egr1 protein, rat; D017874:Immediate-Early Proteins; D012333:RNA, Messenger; D043886:Receptor, Cholecystokinin A; D011949:Receptors, Cholecystokinin; D014157:Transcription Factors; D000661:Amphetamine