Cortical Cannabinoid Modulation of Subcortical Dopamine Activity: Implications for Emotional Processing
Master of Science
Dr. Steven Laviolette
Humans receive countless sensory inputs from the outside world to which they assign a certain level of emotional significance. However, there are times when an individual may assign an abnormally high level of emotional salience to an otherwise non-significant event, resulting in an inappropriate allocation of attention as seen in the hallucinations and psychosis associated with schizophrenia. Several brain regions are involved in this emotional processing, including the medial prefrontal cortex (mPFC) and the ventral tegmental area (VTA). We have previously shown that activation of mPFC cannabinoid (CB1) receptors in rats causes a potentiated fear response to a normally non-salient sensory event (Laviolette & Grace, 2006a). To further investigate the cause of this increased fear response we performed in vivo extracellular electrophysiology recordings along with olfactory fear conditioning in awake, behaving animals. We observed a biphasic effect across both methodologies where an intra-mPFC low dose CB1 agonist caused an increase in spontaneous neural activity in VTA DA cells and a potentiated fear response, while an intra-mPFC high dose CB1 agonist caused a decrease in spontaneous neural activity in VTA DA cells and a block of normal fear memory acquisition, an effect that was rescued using an intra-VTA GABA-B receptor antagonist. Given the implications of the dopamine and cannabinoid systems in schizophrenia, these studies could provide important insights into the underlying neural activity of the emotional processing deficits associated with the disorder
Draycott, Brittany, "Cortical Cannabinoid Modulation of Subcortical Dopamine Activity: Implications for Emotional Processing" (2013). Electronic Thesis and Dissertation Repository. 1580.