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dc.contributor.author
Falzone, Tomas Luis  
dc.contributor.author
Gelman, Diego Matias  
dc.contributor.author
Young, Juan I.  
dc.contributor.author
Grandy, David K.  
dc.contributor.author
Low, Malcolm J.  
dc.contributor.author
Rubinstein, Marcelo  
dc.date.available
2019-07-10T20:38:12Z  
dc.date.issued
2002-01  
dc.identifier.citation
Falzone, Tomas Luis; Gelman, Diego Matias; Young, Juan I.; Grandy, David K.; Low, Malcolm J.; et al.; Absence of dopamine D4 receptors results in enhanced reactivity to unconditioned, but not conditioned, fear; Wiley Blackwell Publishing, Inc; European Journal Of Neuroscience; 15; 1; 1-2002; 158-164  
dc.identifier.issn
0953-816X  
dc.identifier.uri
http://hdl.handle.net/11336/79336  
dc.description.abstract
The prefrontal cortex receives a major dopaminergic input from the ventral tegmental area, which plays an important role in the integration of neuronal signals influencing behavioural responses to stressful environmental stimuli. The dopamine D4 receptor (D4R) is expressed at highest levels in the prefrontal cortex and is the predominant D2-like receptor localized in this brain area. To investigate the functional significance of D4Rs in dopamine-mediated responses we have analysed a strain of mice lacking this receptor subtype (Drd4-/-). Wild-type and Drd4-/- mice were challenged in two different approach/avoidance conflict paradigms: the elevated plus maze and the light/dark preference exploration test. By these behavioural measures Drd4-/- mice showed heightened avoidance to the more fear-provoking areas of each maze as demonstrated by reduced exploration of the open arms of the plus maze and longer latencies to explore the illuminated compartment of the light/dark shuttle box. These exaggerated avoidance behaviours were further enhanced by an additional handling stress but completely prevented by anxiolytic agents such as the benzodiazepine midazolam and ethanol. Although Drd4-/- mice displayed heightened anxiety, they exhibited normal ethanol preference and consumption in a two-bottle choice test. Learned fear responses evaluated by contextual, cued and instrumental fear-conditioning tests showed no difference between wild-type and Drd4-/- mice. Taken together these results indicate that the absence of D4Rs increases avoidance behaviour to unconditioned stimuli and does not impair behavioural reactions to Pavlovian fear-conditioning, suggesting that the D4R could play a key role in the dopaminergic modulation of cortical signals triggered by environmental stimuli.  
dc.format
application/pdf  
dc.language.iso
eng  
dc.publisher
Wiley Blackwell Publishing, Inc  
dc.rights
info:eu-repo/semantics/openAccess  
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/  
dc.subject
Anxiety  
dc.subject
Dopamine Receptors  
dc.subject
Fear  
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Frontal Cortex  
dc.subject
Knockout Mice  
dc.subject
Mouse  
dc.subject.classification
Bioquímica y Biología Molecular  
dc.subject.classification
Ciencias Biológicas  
dc.subject.classification
CIENCIAS NATURALES Y EXACTAS  
dc.title
Absence of dopamine D4 receptors results in enhanced reactivity to unconditioned, but not conditioned, fear  
dc.type
info:eu-repo/semantics/article  
dc.type
info:ar-repo/semantics/artículo  
dc.type
info:eu-repo/semantics/publishedVersion  
dc.date.updated
2019-07-05T17:32:50Z  
dc.journal.volume
15  
dc.journal.number
1  
dc.journal.pagination
158-164  
dc.journal.pais
Reino Unido  
dc.journal.ciudad
Londres  
dc.description.fil
Fil: Falzone, Tomas Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina  
dc.description.fil
Fil: Gelman, Diego Matias. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina  
dc.description.fil
Fil: Young, Juan I.. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina  
dc.description.fil
Fil: Grandy, David K.. Oregon Health Sciences University; Estados Unidos  
dc.description.fil
Fil: Low, Malcolm J.. Oregon Health Sciences University; Estados Unidos  
dc.description.fil
Fil: Rubinstein, Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina  
dc.journal.title
European Journal Of Neuroscience  
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/https://doi.org/10.1046/j.0953-816x.2001.01842.x  
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://onlinelibrary.wiley.com/doi/abs/10.1046/j.0953-816x.2001.01842.x