Conditioned fear is modulated by D2 receptor pathway connecting the ventral tegmental area and basolateral amygdala.
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.
de Oliveira
Amanda Ribeiro
AR
Laboratório de Psicobiologia, Faculdade de Filosofia, Ciências e Letras, Universidade de São Paulo, Ribeirão Preto, SP, Brazil. arobio@usp.br
Reimer
Adriano Edgar
AE
de Macedo
Carlos Eduardo Antunes
CE
de Carvalho
Milene Cristina
MC
Silva
Maria Angélica de Souza
MA
Brandão
Marcus Lira
ML
D000679:Amygdala / Q000187:drug effects / Q000502:physiology*; D000704:Analysis of Variance; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D003213:Conditioning, Psychological / Q000187:drug effects / Q000502:physiology*; D004298:Dopamine / Q000502:physiology*; D018492:Dopamine Antagonists / Q000494:pharmacology; D005239:Fear / Q000187:drug effects / Q000502:physiology*; D046352:Freezing Reaction, Cataleptic / Q000502:physiology; D008297:Male; D017551:Microdialysis; D008845:Microinjections; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D017448:Receptors, Dopamine D2 / Q000502:physiology*; D013216:Reflex, Startle / Q000187:drug effects / Q000502:physiology; D045442:Rotarod Performance Test; D013469:Sulpiride / Q000494:pharmacology; D017557:Ventral Tegmental Area / Q000187:drug effects / Q000502:physiology*
D001552:Benzazepines; D018492:Dopamine Antagonists; D017448:Receptors, Dopamine D2; C534628:SCH 23390; D013469:Sulpiride; D004298:Dopamine