The neurotransmitter dopamine (DA) plays an important role in the brain 'reward' system. Experimental data indicate that DA neurotransmission occurs within two distinct timeframes: tonic and phasic release. Here, we define tonic release as relatively low levels of DA that are maintained over minutes and are likely responsible for the longer-term actions of the neurotransmitter. In contrast, burst firing (less than 1 s) of dopaminergic neurons is predicted to lead to a transient surge of DA release at terminal regions. This subsecond increase in extracellular DA remains until cleared by uptake within less than 5 s. Importantly, it has been proposed that these two distinct forms of DA signaling may regulate different aspects of reward. Tonic changes in DA may be involved in hedonia or incentive salience. In contrast, transient (i.e. subsecond) changes in terminal field DA dynamics may provide an error signal for unexpected rewards that affect learning or promote behavioral switching. While important insight into the role of tonic DA in reinforcement-related processing has been obtained using microdialysis techniques, measurements of short duration changes in DA during goal-directed behaviors have been limited. This is in part related to the fact that not all fast electrochemical techniques selectively measured DA. In our laboratory, fast scan cyclic voltammetry at carbon-fiber microelectrodes has been developed to examine phasic changes in DA during behavior. Importantly, this technique has sufficient time resolution to measure these transient (less than 1 s) changes and is the only fast method with sufficient selectivity to identify DA. The experiments proposed in this application are designed to examine phasic DA release with this tool in the nucleus accumbens (NA) across three reinforcement contexts.
Aim 1 is designed to examine phasic DA during the anticipatory phase of male sexual behavior in rats. Specifically, we will characterize DA transients during presentation of receptive females, non-receptive females, and male rats (Exp 1.1), and determine whether olfactory cues (pheromones) are sufficient to induce DA transients (Exp 1.2).
Aim 2 will characterize DA transients during cocaine self-administration (Exp 2.1) and relative to cocaine-associated stimuli (Exp 2.2), working with Dr. Regina Carelli, Psychology Department, UNC.
Aim 3 consists of three experiments that will determine underlying cellular (Exp 3.1 and 3.2) and behavioral (Exp 3.3) factors mediating the attenuation of phasic DA during intracranial self-stimulation. Collectively, these experiments will provide important insight into the role of phasic DA in reinforcement-related processing.
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