INVESTIGADORES
FALZONE Tomas Luis
artículos
Título:
Absence of Dopamine D4 Receptors Results in Enhanced Reactivity to Unconditioned, But not Conditioned, Fear
Autor/es:
FALZONE T; GELMAN D; YOUNG J; GRANDY D; LOW M; RUBINSTEIN M,
Revista:
EUROPEAN JOURNAL OF NEUROSCIENCE
Editorial:
Blackwell Publishing
Referencias:
Lugar: Cambridge, UK; Año: 2002 vol. 1 p. 158 - 164
ISSN:
0953-816X
Resumen:
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 signi®cance 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