Conditioned fear is modulated by D-2 receptor pathway connecting the ventral tegmental area and basolateral amygdala

Author(s)

de Oliveira, Amanda Ribeiro ^{[1, 2]} ; Reimer, Adriano Edgar ^{[1, 2]} ; Antunes de Macedo, Carlos Eduardo ^[1] ; de Carvalho, Milene Cristina ^{[1, 2]} ; de Souza Silva, Maria Angelica ^[3] ; Brandao, Marcus Lira ^{[1, 2]}

Affiliation

^[1] Campus USP, Inst Neurociencias & Comportamento, Ribeirao Preto, SP - Brazil

^[2] Univ Sao Paulo, Fac Filosofia Ciencias & Letras, Lab Psicobiol, BR-14090901 Ribeirao Preto, SP - Brazil

^[3] Univ Dusseldorf, Inst Expt Psychol, Ctr Behav Neurosci, Dusseldorf - Germany

• Document type: Journal article
• Source: NEUROBIOLOGY OF LEARNING AND MEMORY; v. 95, n. 1, p. 37-45, JAN 2011.
• Web of Science Citations: 46

Abstract

Excitation of the mesocorticolimbic pathway, originating from dopaminergic neurons in the ventral tegmental area (VTA), may be important for the development of exaggerated fear responding. Among the forebrain regions innervated by this pathway, the amygdala is an essential component of the neural circuitry of conditioned fear. The functional role of the dopaminergic pathway connecting the VIA to the basolateral amygdala (BLA) in fear and anxiety has received little attention. In vivo microdialysis was performed to measure dopamine levels in the BLA of Wistar rats that received the dopamine D(2) agonist quinpirole (1 mu g/0.2 mu l) into the VTA and were subjected to a fear conditioning test using a light as the conditioned stimulus (CS). The effects of intra-BLA injections of the D(1) antagonist SCH 23390 (1 and 2 mu g/0.2 mu l) and D(2) antagonist sulpiride (1 and 2 mu g/0.2 mu l) on fear-potentiated startle (FPS) to a light-CS were also assessed. Locomotor performance was evaluated by use of open-field and rotarod tests. Freezing and increased dopamine levels in the BLA in response to the CS were both inhibited by intra-VTA quinpirole. Whereas intra-BLA SCH 23390 did not affect FPS, intra-BLA sulpiride (2 mu g) inhibited FPS. Sulpiride's ability to decrease FPS cannot be attributed to nonspecific effects because this drug did not affect motor performance. These findings indicate that the dopamine D(2) receptor pathway connecting the ventral tegmental area and the basolateral amygdala modulates fear and anxiety and may be a novel pharmacological target for the treatment of anxiety. (C) 2010 Elsevier Inc. All rights reserved. (AU)

• FAPESP's process: 06/06354-5 - Psychobiology of fear and anxiety
• Grantee: Marcus Lira Brandão
• Support Opportunities: Research Projects - Thematic Grants