2013
DOI: 10.1007/s12264-013-1327-x
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Pharmacogenetic activation of midbrain dopaminergic neurons induces hyperactivity

Abstract: Dopaminergic neurons regulate and organize numerous important behavioral processes including motor activity. Consistently, manipulation of brain dopamine concentrations changes animal activity levels. Dopamine is synthesized by several neuronal populations in the brain. This study was carried out to directly test whether selective activation of dopamine neurons in the midbrain induces hyperactivity. A pharmacogenetic approach was used to activate midbrain dopamine neurons, and behavioral assays were conducted … Show more

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Cited by 54 publications
(34 citation statements)
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“…It is well known that a dopamine agonist or increased dopamine signaling produces hyperactivity, e.g. as measured on an open‐field test (Costall et al ., ; Giros et al ., ; Cagniard et al ., ; Wang et al ., ). As dopamine agonists presumably have a net effect of increasing striatal output, as indicated by measures of immediate early genes (Gross & Marshall, ), these observations suggest that an overall increase in striatal output is also correlated with higher movement velocity.…”
Section: Discussionmentioning
confidence: 97%
“…It is well known that a dopamine agonist or increased dopamine signaling produces hyperactivity, e.g. as measured on an open‐field test (Costall et al ., ; Giros et al ., ; Cagniard et al ., ; Wang et al ., ). As dopamine agonists presumably have a net effect of increasing striatal output, as indicated by measures of immediate early genes (Gross & Marshall, ), these observations suggest that an overall increase in striatal output is also correlated with higher movement velocity.…”
Section: Discussionmentioning
confidence: 97%
“…With respect to the specific findings linking the HR‐SE phenotype to the dHPC, lower levels of DA D 1 and 5‐HT 2A receptor mRNA were detected within this region in samples from HR‐SE rats. DA has been heavily implicated in the locomotor response to a novel environment (Beninger, ; Wang et al ., b). Furthermore, data from both animal and human subjects indicates that hypofunction at 5‐HT 2A receptors increases motor impulsivity (Bjork et al ., ; Higgins et al ., ; Winstanley et al ., ,b; Jakubczyk et al ., ).…”
Section: Discussionmentioning
confidence: 99%
“…In this design, it is impossible to separate out the effects of activation of the DREADD from any unexpected effects of CNO, which could be the enhancement or blockade of the expected result of DREADD activation. In terms of dosing, a wide range of doses (0.2–10 mg/kg) is regularly used in DREADD experiments (Alexander et al, 2009; Ferguson et al, 2011, 2013; Ray et al, 2011; Agulhon et al, 2013; Anderson et al, 2013; Farrell et al, 2013; Michaelides et al, 2013; Wang et al, 2013; Boender et al, 2014; Bull et al, 2014; Dell’Anno et al, 2014; Kätzel et al, 2014; Robinson et al, 2014; Zhu et al, 2014; Chang et al, 2015; Gompf et al, 2015; Mizoguchi et al, 2015; Pienaar et al, 2015; Scofield et al, 2015; Yau and McNally, 2015; Grace et al, 2016; Ma et al, 2016; Marchant et al, 2016; Qiu et al, 2016; Sengupta et al, 2016; Wicker and Forcelli, 2016), and there is seldom any explanation given as to how the dose that was used was decided upon. Using the lowest effectual dose in the assay to be performed, that which in the non-DREADD-expressing animals is experimentally silent, would seem the most straightforward way to minimize any off-target effects of CNO.…”
Section: Relevance To the Dreadd System: Is Cno An Inert Ligand?mentioning
confidence: 99%