title: Dose-response analysis of locomotor activity and stereotypy in dopamine D3 receptor mutant mice following acute amphetamine.
abstract: Accumulating evidence suggests that dopamine D3 receptor (D3R) stimulation is inhibitory to spontaneous and psychostimulant-induced locomotion through opposition of concurrent D1R and D2R-mediated signaling. To evaluate this model, we used homozygous D3R mutant mice and wild-type controls to investigate the role of the D3R in locomotor activity and stereotypy stimulated by acute amphetamine (AMPH) (0.2, 2.5, 5.0, 10.0 mg/kg). At the lowest dose tested (0.2 mg/kg), neither D3R mutant mice nor wild-type mice exhibited measurable change in locomotor activity or stereotypy relative to their respective saline-treated controls. D3R mutant mice exhibited a significantly greater increase in locomotor activity, but not stereotypy, relative to wild-type mice in response to treatment with AMPH 2.5 mg/kg. AMPH-induced locomotor activity and stereotypy were similar in both wild-type and D3R mutant mice at both the 5.0 and 10 mg/kg AMPH doses. These findings provide further support for an inhibitory role for the D3R in AMPH-induced locomotor activity, and demonstrate a more limited role for the D3R in modulating AMPH-induced stereotypy.
authors.affiliation: Department of Psychiatry, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267, USA. robert.mcnamara@psychiatry.uc.edu
authors.forename: Robert K
authors.initials: RK
authors.lastname: McNamara
authors.forename: Aaron
authors.initials: A
authors.lastname: Logue
authors.forename: Kevin
authors.initials: K
authors.lastname: Stanford
authors.forename: Ming
authors.initials: M
authors.lastname: Xu
authors.forename: Jianhua
authors.initials: J
authors.lastname: Zhang
authors.forename: Neil M
authors.initials: NM
authors.lastname: Richtand
mesh_terms: D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D001923:Brain Chemistry / Q000187:drug effects / Q000235:genetics*; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism*; D015259:Dopamine Agents / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity / Q000187:drug effects / Q000235:genetics*; D009433:Neural Inhibition / Q000187:drug effects / Q000235:genetics; D050637:Receptors, Dopamine D3 / Q000819:agonists / Q000235:genetics*; D019956:Stereotypic Movement Disorder / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D009435:Synaptic Transmission / Q000187:drug effects / Q000235:genetics
chemical_list: D015259:Dopamine Agents; D050637:Receptors, Dopamine D3; D000661:Amphetamine; D004298:Dopamine