The extracellular fluid of the striatum contains a high level of ascorbate, an antioxidant vitamin known to play a key role in behavioral activation. We assessed the extracellular dynamics of ascorbate in R6/2 mice engineered to express the gene for Huntington's disease (HD), an autosomal dominant condition characterized by the loss of striatal neurons. Slow-scan voltammetry was used to measure striatal ascorbate during anesthesia and subsequent behavioral recovery. Although both the HD mice and their littermate controls had comparable ascorbate levels during anesthesia, the gradual return of behavioral activation over the next 120 min led to dramatically different ascorbate responses: a progressive increase in controls and a 25-50% decline in HD mice. In contrast, 3,4-dihydroxyphenylacetic acid, a major dopamine metabolite, showed no group differences. Behaviorally, HD mice were less active overall than controls and showed a relatively restricted range of spontaneous movements. Both the ascorbate and behavioral deficits were evident in 6-week-old HD mice and persisted in all subsequent test sessions through 10 weeks of age. Collectively, although these results are consistent with inadequate antioxidant protection in the HD striatum, they indicate that the ascorbate deficit is confined to periods of behavioral activation.
Historically, cognitive-developmental and behavior-analytic approaches to the study of human behavior change and development have been presented as incompatible alternative theoretical and methodological perspectives. This presumed incompatibility has been understood as arising from divergent sets of metatheoretical assumptions that take the form of ontological and epistemological principles, and constitute worldviews. Classically, cognitive-developmental approaches have been cast as deriving from an organismic worldview and behavior-analytic approaches from a contextualist worldview. Previous attempts at uniting the two approaches have entailed privileging one and radically modifying the other. The present paper argues that a meaningful integration requires a set of metatheoretical assumptions that transcends both worldviews, and, while maintaining their distinct qualities, unites them. This metatheoretical framework termed relational metatheory is described and its integrative implications explained.
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