Abstract
RationaleTrace conditioning may provide a behavioural model suitable to examine the maintenance of ‘on line’ information and its underlying neural substrates.ObjectivesExperiment la was run to establish trace conditioning in a shortened procedure which would be suitable to test the effects of dopamine (DA) D1 receptor agents administered by microinjection directly into the brain. Experiment lb examined the effects of the DA D1 agonist SKF81297 and the DA D1 antagonist SCH23390 following systemic administration in pre-trained animals. Experiment 2 went on to test the effects of systemically administered SKF81297 on the acquisition of trace conditioning. In experiment 3, SKF81297 was administered directly in prelimbic (PL) and infralimbic (IL) sub-regions of medial prefrontal cortex (mPFC) to compare the role of different mPFC sub-regions.ResultsWhilst treatment with SCH23390 impaired motor responding and/or motivation, SKF81297 had relatively little effect in the pre-trained animals tested in experiment 1b. However, systemic SKF81297 depressed the acquisition function at the 2-s trace interval in experiment 2. Similarly, in experiment 3, SKF81297 (0.1 μg in 1.0 μl) microinjected into either PL or IL mPFC impaired appetitive conditioning at the 2-s trace interval.ConclusionsImpaired trace conditioning under SKF81297 is likely to be mediated in part (but not exclusively) within the IL and PL mPFC sub-regions. The finding that trace conditioning was impaired rather than enhanced under SKF81297 provides further evidence for the inverse U-function which has been suggested to be characteristic of mPFC DA function.
Highlights
Working memory has been defined as the capacity to maintain ‘on line’ transitory information in order to allow comprehension, thinking and planning (Goldman-Rakic 1996)
Impaired trace conditioning under SKF81297 is likely to be mediated in part within the IL and PL medial prefrontal cortex (mPFC) sub-regions
The finding that trace conditioning was impaired rather than enhanced under SKF81297 provides further evidence for the inverse U-function which has been suggested to be characteristic of mPFC DA function
Summary
Working memory has been defined as the capacity to maintain ‘on line’ transitory information in order to allow comprehension, thinking and planning (Goldman-Rakic 1996). Working memory provides a likely mechanism for associative processes in general, and, in particular, when a time interval must be bridged (Gilmartin et al 2014). With respect to underlying brain substrates, deficits in working memory have been attributed to neuronal loss in medial prefrontal (mPFC) dopamine (DA) pathways (Arnsten et al 1994; Cai and Arnsten 1997; Goldman-Rakic and Brown 1981; Harada et al 2002; Robbins and Arnsten 2009). Consistent with the role of DA as a modulator of aspects of mPFC function, DA depletion in the caudate nucleus impaired spatial delayed response task performance (Collins et al 2000). Whilst as an entity mPFC has been implicated in working memory and temporal processes, the roles of its specific sub-regions in mediating temporal aspects of working memory, and in particular the role of DA within specific sub-regions, have yet to be fully established (Cassaday et al 2014)
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