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

Laboratório de Psicobiologia, Faculdade de Filosofia, Ciências e Letras, Universidade de São Paulo, Ribeirão Preto, SP, Brazil.
Neurobiology of Learning and Memory (Impact Factor: 4.04). 10/2010; 95(1):37-45. DOI: 10.1016/j.nlm.2010.10.005
Source: PubMed

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 VTA 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 μg/0.2 μl) 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 μg/0.2 μl) and D(2) antagonist sulpiride (1 and 2 μg/0.2 μl) 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 μg) 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.

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    • "Moreover, D2 (but not D1) antagonists injection in the BLa impairs fear-potentiated startle probably due to reduced dopaminergic tone (de Oliveira et al. 2011), which is in agreement with the amygdalar hypodopaminergic status seen in DEX-exposed animals. These findings are consistent with recent data showing that D2 receptor pathway connecting the VTA and BLa modulates conditioned fear (de Oliveira et al. 2011). "
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