Saturday, May 18, 2024
5/18/2024
It is well-known that an imbalance in activity between that patch and matrix systems of striatum underlies inflexible and repetitive behaviors, such as psychostimulant-induced stereotypy. Habitual drug abuse is also persistent and inflexible, raising the possibility that addiction is mediated by the patch-matrix system. Furthermore, previous work suggests that the patch system carries information relating to reward, which may also contribute to the eventual development of habitual drug use. We posit that habit formation, as well as psychostimulant reward are due to predominant activation of the patch versus matrix system, which occurs due to the weakening of synaptic connections in matrix-based circuits. The goal of this application is to determine contribution of the patch-matrix system to habitual behaviors, as well as reward processes. Specific Aim 1 will examine whether an imbalance in patch-matrix activity contributes to METH- mediated reward and habit formation. Specific Aim 2 will examine changes in synaptic plasticity that might underlie imbalanced activity in the patch vs. matrix compartments following METH-mediated reward and habit formation. Specific Aim 3 will investigate intracellular mediators that might contribute to the imbalance in patch-matrix activity that is seen with METH-mediated reward and habit formation. The proposed research is innovative because the patch- matrix system has not been examined as a possible pathway for reward and the development of habitual behaviors. Moreover, the specific contribution of patch-based circuits to drug reward has not been described, and therefore represents a novel pathway for drug-related reward processes. We expect the outcomes of these experiments will greatly add to our understanding of the neural systems that mediate habitual drug abuse.
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