Craig F. Ferris

Northeastern University, USA

Abstract

[O23] Functional MRI Studies on the Role of Vasopressin in Aggressive Motivation and Fear Conditioning

Functional MRI in wake male rats combined with 3D computational analysis were  used to identifying the putative integrated neural circuits involved in aggressive motivation and fear conditioning and how these circuits are affected by vasopressin signaling in the brain.  Aggressive motivation was triggered by exposing a resident male being imaged to their female mate together with a strange male intruder in the bore of the magnet. Conditioned fear was elicited by the presentation of a ferret in the magnet while applying sucrose to the tongue.  Weeks later a robust fear response could be elicited by simply applying sucrose to the tongue during an imaging session.

Brain areas previously identified as critical in the organization and expression of aggressive behavior were activated by the presence of the male intruder.  Unexpected was the intense activation of the forebrain cortex and anterior thalamic nuclei.  Oral administration of a selective vasopressin V1a receptor antagonist SRX251 caused a general suppression of the distributed neural circuit involved in aggressive motivation.  However, the effect of SRX251 was specific to aggression as brain activation in response to a novel sexually receptive female was unaffected.

Interestingly, the initial exposure to fear showed high activation of the limbic cortex and thalamus but little amygdala.  Vasopressin receptor blockade had no effect on the unconditioned fear response.  However, rats conditioned to sucrose showed a much greater increase in brain activation as compared to the ferret alone. With conditioning came a greater increase in activity in the amygdala and prefrontal cortex.  Vasopressin receptor blockade reduced thalamic and cortical activation associated with fear conditioning.

The putative neural circuits of aggressive motivation and fear conditioning toward a predator both include areas involved in emotional experience (i.e. hippocampus, forebrain cortex, anterior cingulate, retrosplenial cortex) and the anterior thalamic nuclei that bridge the motor and cognitive components of aggression and fear.  Drugs that block vasopressin neurotransmission suppress activity in many of these common areas.