Imaging the neural circuitry and chemical control of aggressive motivation.
BACKGROUND
With the advent of functional magnetic resonance imaging (fMRI) in awake animals it is possible to resolve patterns of neuronal activity across the entire brain with high spatial and temporal resolution. Synchronized changes in neuronal activity across multiple brain areas can be viewed as functional neuroanatomical circuits coordinating the thoughts, memories and emotions for particular behaviors. To this end, fMRI in conscious rats combined with 3D computational analysis was used to identifying the putative distributed neural circuit involved in aggressive motivation and how this circuit is affected by drugs that block aggressive behavior.


RESULTS
To trigger aggressive motivation, male rats were presented with their female cage mate plus a novel male intruder in the bore of the magnet during image acquisition. As expected, brain areas previously identified as critical in the organization and expression of aggressive behavior were activated, e.g., lateral hypothalamus, medial basal amygdala. Unexpected was the intense activation of the forebrain cortex and anterior thalamic nuclei. Oral administration of a selective vasopressin V1a receptor antagonist SRX251 or the selective serotonin reuptake inhibitor fluoxetine, drugs that block aggressive behavior, both caused a general suppression of the distributed neural circuit involved in aggressive motivation. However, the effect of SRX251, but not fluoxetine, was specific to aggression as brain activation in response to a novel sexually receptive female was unaffected.


CONCLUSIONS
The putative neural circuit of aggressive motivation identified with fMRI includes neural substrates contributing to emotional expression (i.e. cortical and medial amygdala, BNST, lateral hypothalamus), emotional experience (i.e. hippocampus, forebrain cortex, anterior cingulate, retrosplenial cortex) and the anterior thalamic nuclei that bridge the motor and cognitive components of aggressive responding. Drugs that block vasopressin neurotransmission or enhance serotonin activity suppress activity in this putative neural circuit of aggressive motivation, particularly the anterior thalamic nuclei.
Ferris
Craig F
CF
Center for Translational NeuroImaging, Northeastern University, Boston, Massachusetts, USA. c.ferris@neu.edu
Stolberg
Tara
T
Kulkarni
Praveen
P
Murugavel
Murali
M
Blanchard
Robert
R
Blanchard
D Caroline
DC
Febo
Marcelo
M
Brevard
Mathew
M
Simon
Neal G
NG
D000284:Administration, Oral; D000374:Aggression / Q000187:drug effects / Q000502:physiology / Q000523:psychology*; D000679:Amygdala / Q000033:anatomy & histology / Q000187:drug effects / Q000502:physiology; D000818:Animals; D065092:Antidiuretic Hormone Receptor Antagonists; D001921:Brain / Q000033:anatomy & histology / Q000187:drug effects / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005473:Fluoxetine / Q000008:administration & dosage / Q000494:pharmacology; D007031:Hypothalamus / Q000033:anatomy & histology / Q000187:drug effects / Q000502:physiology; D007091:Image Processing, Computer-Assisted; D021621:Imaging, Three-Dimensional; D008279:Magnetic Resonance Imaging; D008297:Male; D009042:Motivation; D009415:Nerve Net / Q000033:anatomy & histology / Q000187:drug effects / Q000502:physiology*; D016548:Prosencephalon / Q000033:anatomy & histology / Q000187:drug effects / Q000502:physiology; D051381:Rats; D020318:Rats, Long-Evans; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D013788:Thalamus / Q000033:anatomy & histology / Q000187:drug effects / Q000502:physiology
D065092:Antidiuretic Hormone Receptor Antagonists; D005473:Fluoxetine; D017367:Selective Serotonin Reuptake Inhibitors