Role of dopamine receptor mechanisms in the amygdaloid modulation of fear and anxiety: Structural and functional analysis.
Dopamine plays an important role in fear and anxiety modulating a cortical brake that the medial prefrontal cortex exerts on the anxiogenic output of the amygdala and have an important influence on the trafficking of impulses between the basolateral (BLA) and central nuclei (CeA) of amygdala. Dopamine afferents from the ventral tegmental area innervate preferentially the rostrolateral main and paracapsular intercalated islands as well as the lateral central nucleus of amygdala activating non-overlapping populations of D1- and D2-dopamine receptors located in these structures. Behaviorally, the intra-amygdaloid infusion of D1 agonists and antagonists elicits anxiogenic and anxiolytic effects respectively on conditioned and non-conditioned models of fear/anxiety suggesting an anxiogenic role for D1 receptors in amygdala. The analysis of the effects of D2 agonists and antagonists suggest that depending of the nature of the threat the animal experiences in anxiety models either anxiogenic or anxiolytic effects are elicited. It is suggested that D1- and D2-dopamine receptors in the amygdala may have a differential role in the modulation of anxiety. The possibility is discussed that D1 receptors participate in danger recognition facilitating conditioned-unconditioned associations by the retrieval of the affective properties of the unconditioned stimuli, and in the control of impulse trafficking from cortical and BLA regions to BLA and CeA nuclei respectively whereas D2 receptors have a role in setting up adaptive responses to cope with aversive environmental stimuli.
Department of Biophysics, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Apartado Postal 70-253, México DF 04510, Mexico. mperez@ifc.unam.mx
Miguel Pérez
MP
de la Mora
Andrea
A
Gallegos-Cari
Yexel
Y
Arizmendi-García
Daniel
D
Marcellino
Kjell
K
Fuxe
D000679:Amygdala / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D001007:Anxiety / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D015259:Dopamine Agents / Q000494:pharmacology; D005239:Fear; D006801:Humans; D011954:Receptors, Dopamine / Q000502:physiology*; D013329:Structure-Activity Relationship
D015259:Dopamine Agents; D011954:Receptors, Dopamine