TY - JOUR
T1 - Dual role of dopamine D2-like receptors in the mediation of conditioned and unconditioned fear
AU - Brandão, Marcus Lira
AU - De Oliveira, Amanda Ribeiro
AU - Muthuraju, Sangu
AU - Colombo, Ana Caroline
AU - Saito, Viviane Mitsuko
AU - Talbot, Teddy
N1 - Publisher Copyright:
© 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
PY - 2015/1/20
Y1 - 2015/1/20
N2 - A reduction of dopamine release or D2 receptor blockade in the terminal fields of the mesolimbic system, particularly the amygdala, clearly reduces conditioned fear. Similar D2 receptor antagonism in the neural substrates of fear in the midbrain tectum attenuates the processing of unconditioned aversive information. However, the implications of the interplay between opposing actions of dopamine in the rostral and caudal segments of the dopaminergic system are still unclear. Previous studies from this laboratory have reported the effects of dopaminergic drugs on behavior in rats in the elevated plus maze, auditory-evoked potentials (AEPs) recorded from the midbrain tectum, fear-potentiated startle, and conditioned freezing. These findings led to an interesting framework on the functional roles of dopamine in both anxiety and fear states. Dopamine D2 receptor inhibition in the terminal fields of the mesolimbic dopamine system generally causes anxiolytic-like effects, whereas the activity of midbrain substrates of unconditioned fear are enhanced by D2 receptor antagonists, suggesting that D2 receptor-mediated mechanisms play opposing roles in fear/anxiety processes, depending on the brain region under study. Dopamine appears to mediate conditioned fear by acting at rostral levels of the brain and regulate unconditioned fear at the midbrain level, likely by reducing the sensorimotor gating of aversive events.
AB - A reduction of dopamine release or D2 receptor blockade in the terminal fields of the mesolimbic system, particularly the amygdala, clearly reduces conditioned fear. Similar D2 receptor antagonism in the neural substrates of fear in the midbrain tectum attenuates the processing of unconditioned aversive information. However, the implications of the interplay between opposing actions of dopamine in the rostral and caudal segments of the dopaminergic system are still unclear. Previous studies from this laboratory have reported the effects of dopaminergic drugs on behavior in rats in the elevated plus maze, auditory-evoked potentials (AEPs) recorded from the midbrain tectum, fear-potentiated startle, and conditioned freezing. These findings led to an interesting framework on the functional roles of dopamine in both anxiety and fear states. Dopamine D2 receptor inhibition in the terminal fields of the mesolimbic dopamine system generally causes anxiolytic-like effects, whereas the activity of midbrain substrates of unconditioned fear are enhanced by D2 receptor antagonists, suggesting that D2 receptor-mediated mechanisms play opposing roles in fear/anxiety processes, depending on the brain region under study. Dopamine appears to mediate conditioned fear by acting at rostral levels of the brain and regulate unconditioned fear at the midbrain level, likely by reducing the sensorimotor gating of aversive events.
KW - Anxiety
KW - Brain aversion system
KW - Conditioned fear
KW - Dopamine
KW - Panic
KW - Unconditioned fear
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U2 - 10.1016/j.febslet.2015.02.036
DO - 10.1016/j.febslet.2015.02.036
M3 - Review article
C2 - 25783771
AN - SCOPUS:84946489062
SN - 0014-5793
VL - 589
SP - 3433
EP - 3437
JO - FEBS Letters
JF - FEBS Letters
IS - 22
ER -