title: Dual role of dopamine D(2)-like receptors in the mediation of conditioned and unconditioned fear.
abstract: 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.
authors.affiliation: Laboratório de Neuropsicofarmacologia, FFCLRP, Universidade de São Paulo, Campus USP, Ribeirão Preto, SP, Brazil; Instituto de Neurociências e Comportamento, Avenida do Café, 2450, Ribeirão Preto, SP, Brazil. Electronic address: mbrandao@usp.br.
authors.forename: Marcus Lira
authors.initials: ML
authors.lastname: Brandão
authors.affiliation: Laboratório de Neuropsicofarmacologia, FFCLRP, Universidade de São Paulo, Campus USP, Ribeirão Preto, SP, Brazil; Instituto de Neurociências e Comportamento, Avenida do Café, 2450, Ribeirão Preto, SP, Brazil.
authors.forename: Amanda Ribeiro
authors.initials: AR
authors.lastname: de Oliveira
authors.affiliation: Laboratório de Neuropsicofarmacologia, FFCLRP, Universidade de São Paulo, Campus USP, Ribeirão Preto, SP, Brazil; Instituto de Neurociências e Comportamento, Avenida do Café, 2450, Ribeirão Preto, SP, Brazil.
authors.forename: Sangu
authors.initials: S
authors.lastname: Muthuraju
authors.affiliation: Laboratório de Neuropsicofarmacologia, FFCLRP, Universidade de São Paulo, Campus USP, Ribeirão Preto, SP, Brazil; Instituto de Neurociências e Comportamento, Avenida do Café, 2450, Ribeirão Preto, SP, Brazil.
authors.forename: Ana Caroline
authors.initials: AC
authors.lastname: Colombo
authors.affiliation: Laboratório de Neuropsicofarmacologia, FFCLRP, Universidade de São Paulo, Campus USP, Ribeirão Preto, SP, Brazil; Instituto de Neurociências e Comportamento, Avenida do Café, 2450, Ribeirão Preto, SP, Brazil.
authors.forename: Viviane Mitsuko
authors.initials: VM
authors.lastname: Saito
authors.affiliation: Laboratório de Neuropsicofarmacologia, FFCLRP, Universidade de São Paulo, Campus USP, Ribeirão Preto, SP, Brazil; Instituto de Neurociências e Comportamento, Avenida do Café, 2450, Ribeirão Preto, SP, Brazil.
authors.forename: Teddy
authors.initials: T
authors.lastname: Talbot
mesh_terms: D000818:Animals; D003213:Conditioning, Psychological; D004298:Dopamine / Q000378:metabolism; D005239:Fear / Q000523:psychology*; D006801:Humans; D017448:Receptors, Dopamine D2 / Q000378:metabolism*
chemical_list: D017448:Receptors, Dopamine D2; D004298:Dopamine
keywords: Anxiety; Brain aversion system; Conditioned fear; Dopamine; Panic; Unconditioned fear