Dual role of dopamine D₂‐like receptors in the mediation of conditioned and unconditioned fear

Abstract

a b s t r a c tA reduction of dopamine release or D 2 receptor blockade in the terminal fields of the mesolimbic system, particularly the amygdala, clearly reduces conditioned fear. Similar D 2 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 D 2 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 D 2 receptor antagonists, suggesting that D 2 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.

Anxiety reduction on atomoxetine and methylphenidate medication in children with ADHD

“…These have included the baseline sympathetic tone decrease and cardiac parasympathetic tone elevation and slowing down of the sympathetic arousal to acute stress . The anxiolytic effects of methylphenidate could also be mediated via central norepinephrine re‐uptake inhibition, but the anxiolytic properties could be reduced by its dopaminergic effects on rostral segments of the dopaminergic system, in which the increased dopamine activity has been associated with conditioned fear . This could explain why we found less but still highly significantly reduced anxiety symptoms in children treated with methylphenidate compared with those on atomoxetine.…”

Regulation of Fear Extinction in the Basolateral Amygdala by Dopamine D2 Receptors Accompanied by Altered GluR1, GluR1-Ser845 and NR2B Levels

“…Biochemical analyses of dialysate from the amygdala have revealed that DA release can be induced by electric footshock (Muller et al, 2009). This increased DA level excites BLA pyramidal cells, and a decrease in dopamine activity in the BLA reduces the expression of conditioned fear (Brandão et al, 2015). Because quinpirole inhibits DA release, we speculated that the reduction in DA suppresses the activity of pyramidal cells in the BLA.…”

Mesocorticolimbic dopamine functioning in primary psychopathy: A source of within-group heterogeneity

“…In other words, the active role of DA in emotion is likely evaluative, attention-mediated, and anticipatory (stronger role towards conditioned stimuli), rather than acute, intuitive, and automated (both conditioned and unconditioned stimuli), which corresponds to the distinction between, respectively, anxiety and fear (Grillon, 2008). Nonetheless, to nuance this statement, basal DA activity does seem to have a passive role in the sensorimotor gating of unconditioned aversive material via D2-receptors in the midbrain (Brandão et al, 2015).…”