KOLB, EM; RHODES, JS; JANOWSKY, A; GARLAND, T; Univ. of Calif., Riverside; Oregon Health and Sciences Univ. ; Oregon Health and Sciences Univ. ; Univ. of Calif., Riverside: Dopamine Receptor and Transporter Density in the Caudate and Prefrontal Cortex of Mice Selectively Bred for High Wheel Running
Animals that exhibit high locomotor activity must have both the physical ability for sustained exercise and the “motivation” to initiate and sustain high activity. We have used selective breeding to develop a model in which to study both of these aspects, 4 lines of house mice bred for High Running distance on wheels (HR) and 4 bred randomly as controls (C). The mammalian dopamine system in the CNS is known to play a necessary role in both locomotion and motivation. HR mice are differentially sensitive to dopamine drugs (methylphenidate [Ritalin], cocaine, GBR 12909, apomorphine), including the dopamine D1-like receptor antagonist SCH 23390, but not to opiate drugs (naloxone, naltrexone) or the serotonin drug fluoxetine (Psychopharmacology 158:120-131 and 167:242-250). The mechanism underlying the dopamine-related differences is presently unknown, but could involve dopamine receptors and/or reuptake transporters, among many other possibilities. Two brain regions in which dopamine signals are known to affect locomotor activity and incentive motivation are the caudate and prefrontal cortex. Indeed, these regions display increased levels of c-Fos in HR vs C when wheel access is prevented (Behav Neurosci 117:1243-1256). Here, we evaluate the concentration of specific types of dopamine receptors (D1-like vs D2-like) and reuptake transporter proteins in the caudate and prefrontal cortex of HR and C lines under baseline conditions (i.e., no wheel access). The assay uses protein-specific radioactive labels to measure maximum binding as an indicator of protein density. The trait demonstrates substantial heritability in a panel of recombinant inbred strains (J Pharmacol Exp Ther 298:634-643). Supported by NSF IBN-0212567 to TG and NIH/VA Y1DA0107 to A.J.
