This is an application for a CEBRA award from NIDA. Understanding neural mechanisms of addiction will likely involve determining how normal brain mechanisms of emotional memory formation contribute to the disorder. The amygdala is known to be crucial for emotional memory, and many intriguing links exist between addiction and amygdala function in emotional memory. For example, activity of dopamine (DA), a neurotransmitter heavily implicated in addiction, within the amygdala clearly influences emotional memory formation. However, despite their likely importance, dopaminergic mechanisms within the human amygdala remain almost completely unexplored at present, and their relations to emotional memory and addiction are not known. This gap in our knowledge results primarily from the fact that ligands used to date to study human dopaminergic function with positron emission tomography (PET) scanning lack sufficient sensitivity to accurately and reliably assess amygdala activity. Recently, however and colleagues (2002a) developed a specific D2/D3 ligand-18F-fallypride- capable of reliably detecting D2/D3 receptor related activity in the human amygdala. Development of this method has created a new opportunity to study DA mechanisms within the human amygdala (and related brain regions) with respect to both to normal mechanisms of emotional memory and to addiction. Here we propose to combine the expertise of the PI in human amygdala function in emotional memory, with that of the Co-PI in the 18F-fallypride PET method to investigate the responsiveness of DA within the human amygdala to emotional learning conditions in both men and women. The primary goal of this proposal is to determine whether endogenous dopamine release within the human amygdala (and related regions) in response to the emotional memory challenges used in our previous studies can be detected with the (18)F-fallypride method. In addition, we propose to begin determining how both the variables of sex and cerebral hemisphere influence these mechanisms. The data derived from these preliminary experiments should lay the foundation for a research program aimed at understanding how DA mechanisms within the human amygdala subserve both emotional memory and addiction.
