Dopamine modulates individual differences in avoidance behavior: A pharmacological, immunohistochemical, neurochemical and volumetric investigation.

Autor: Antunes GF; Division of Neuroscience, Hospital Sirio-Libanes, Sao Paulo, Brazil., Gouveia FV; Division of Neuroscience, Hospital Sirio-Libanes, Sao Paulo, Brazil., Rezende FS; Division of Neuroscience, Hospital Sirio-Libanes, Sao Paulo, Brazil., Seno MDJ; Division of Neuroscience, Hospital Sirio-Libanes, Sao Paulo, Brazil., de Carvalho MC; University of Sao Paulo and Institute of Neuroscience and Behavior (INeC), Campus USP, Ribeirao Preto, Brazil., de Oliveira CC; Division of Neuroscience, Hospital Sirio-Libanes, Sao Paulo, Brazil., Dos Santos LCT; Division of Neuroscience, Hospital Sirio-Libanes, Sao Paulo, Brazil., de Castro MC; Division of Neuroscience, Hospital Sirio-Libanes, Sao Paulo, Brazil., Kuroki MA; Division of Neuroscience, Hospital Sirio-Libanes, Sao Paulo, Brazil., Teixeira MJ; Department of Neurology, Division of Functional Neurosurgery, Institute of Psychiatry, University of Sao Paulo School of Medicine, Sao Paulo, Brazil., Otoch JP; Department of Surgery Techniques, School of Medicine, University of Sao Paulo, Sao Paulo, Brazil., Brandao ML; University of Sao Paulo and Institute of Neuroscience and Behavior (INeC), Campus USP, Ribeirao Preto, Brazil., Fonoff ET; Department of Neurology, Division of Functional Neurosurgery, Institute of Psychiatry, University of Sao Paulo School of Medicine, Sao Paulo, Brazil., Martinez RCR; Division of Neuroscience, Hospital Sirio-Libanes, Sao Paulo, Brazil.; LIM/23 - Laboratório de Psicopatologia e Terapêutica Psiquiátrica, Institute of Psychiatry, University of Sao Paulo School of Medicine, Sao Paulo, Brazil.; UNICID - Universidade Cidade de São Paulo, Sao Paulo, Brazil.
Jazyk: angličtina
Zdroj: Neurobiology of stress [Neurobiol Stress] 2020 Apr 08; Vol. 12, pp. 100219. Date of Electronic Publication: 2020 Apr 08 (Print Publication: 2020).
DOI: 10.1016/j.ynstr.2020.100219
Abstrakt: Avoidance behavior is a hallmark in pathological anxiety disorders and results in impairment of daily activities. Individual differences in avoidance responses are critical in determining vulnerability or resistance to anxiety disorders. Dopaminergic activation is implicated in the processing of avoidance responses; however, the mechanisms underlying these responses are unknown. In this sense, we used a preclinical model of avoidance behavior to investigate the possibility of an intrinsic differential dopaminergic pattern between good and poor performers. The specific goal was to assess the participation of dopamine (DA) through pharmacological manipulation, and we further evaluated the effects of systemic injections of the dopaminergic receptor type 1 (D1 antagonist - SCH23390) and dopaminergic receptor type 2 (D2 antagonist - sulpiride) antagonists in the good performers. Additionally, we evaluated the effects of intra-amygdala microinjection of a D1 antagonist (SCH23390) and a D2 antagonist (sulpiride) in good performers as well as intra-amygdala microinjection of a D1 agonist (SKF38393) and D2 agonist (quinpirole) in poor performers. Furthermore, we quantified the contents of dopamine and metabolites (3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA)) in the amygdala, evaluated the basal levels of tyrosine hydroxylase expression (catecholamine synthesis enzyme) and measured the volume of the substantia nigra, ventral tegmental area and locus coeruleus. Our results showed that it could be possible to convert animals from good to poor performers, and vice versa, by intra-amygdala (basolateral and central nucleus) injections of D1 receptor antagonists in good performers or D2 receptor agonists in poor performers. Additionally, the good performers had lower levels of DOPAC and HVA in the amygdala, an increase in the total volume of the amygdala (AMG), substantia nigra (SN), ventral tegmental area (VTA) and locus coeruleus (LC), and an increase in the number of tyrosine hydroxylase-positive cells in SN, VTA and LC, which positively correlates with the avoidance behavior. Taken together, our data show evidence for a dopaminergic signature of avoidance performers, emphasizing the role of distinct dopaminergic receptors in individual differences in avoidance behavior based on pharmacological, immunohistochemical, neurochemical and volumetric analyses. Our findings provide a better understanding of the role of the dopaminergic system in the execution of avoidance behavior.
Competing Interests: The authors report no conflicts of interest.
(© 2020 The Authors.)
Databáze: MEDLINE