Characterization of the dopamine role in the mediation of distinct kinds of fear

Abstract

Chemical and electrical stimulation of the periaqueductal gray matter (PAG), deep layer of Superior colliculus (dlSC) and the central nucleus of the inferior colliculus (CIC) of rodents cause freezing and escape behavior. Following electrical stimulation of these structures, the animal shows intense flight and explosive behavior. It is believed that the defensive reactions associated with these structures may be representative of panic attacks in humans whereas the immobility after their electrical stimulation is associated with panic disorder. Electrical stimulation of the CIC at the escape threshold enhances dopamine (DA) release in the prefrontal cortex. Blocking dopamine receptors in the CIC enhances unconditioned fear. It is also known that systemic injection of sulpiride (a dopamine antagonist) increased the number of switch off responses. Based on these data, in this project we will investigate the role of the dopaminergic mechanisms of these structures in the defense reaction. Recent evidence from this laboratory gives support to the aims of this project; i) Systemic and local injection of haloperidol into the CIC enhanced unconditioned fear ii) In the light-induced switch off test, apomorphine reduced the number of switch off responses whereas sulpiride increased the responses iii) preliminary findings suggested that sulpiride produced escape behavior following injection into the CIC, iv) Aversive auditory stimuli alone produced significant Fos expression in PAG especially in dorsomedial PAG (dmPAG), dorsolateral PAG (dlPAG) and CIC. Specifically, we will examine the involvement of the D1, D2 receptors-mediated mechanisms in the above mentioned structures during fear states by using behavioral (elevated plus-maze and switch-off response to light), electrophysiologically (auditory evoked potentials), and Immunohistochemical (Fos expression in a series of limbic structures) techniques.