This project will assess excitatory synaptic transmission in WT and Taar1 KO rats in the context of the incubation of craving model. Incubation (the time-dependent increase in cue induced craving that occurs after discontinuing drug self-administration) occurs in rodents and humans, so the model is translationally relevant and is increasingly used to study mechanisms responsible for the persistence of drug craving even after long periods of abstinence.
This project will test the hypothesis that incubation of MA craving involves potentiation of glutamate synapses onto VTA dopamine neurons leading to enhanced cue-induced dopamine release in NAc core, and that Taar1 deletion exacerbates incubation of MA craving and these underlying cellular events. The work will be done using cutting edge approaches including the genetically encoded dopamine sensor dLight, transgenic rat lines, and state-of-the-art electrophysiological approaches. Results from Project P003 will inform and be informed by studies on how MA signals through TAAR1 in dopamine cells and how VTA/NAc connectivity is affected during incubation of craving, as well as studies of TAAR1 and MA craving in humans.
Aim 1: Determine the role of TAAR1 in the incubation of MA craving.
Aim 2: Characterize MA-induced excitatory synaptic plasticity in VTA DA neurons.
Aim 3: Measure cue-induced DA release in the NAc core during the incubation of MA craving.