| Parkinson's disease (PD) is often treated with D2/D3 receptor-preferring agonists such as pramipexole (PPX). Impulse control disorders (ICDs) are a debilitating side effect of dopamine agonist treatment in some treated PD patients. The biological substrates that underlie PPX-induced ICDs in PD remain unclear. We previously demonstrated in normal rats that acute administration of PPX alters signaling in the Akt/GSK30 pathway by decreasing phosphorylation of Akt and GSK30 in the nucleus accumbens (NAc), a D3-rich brain region involved in reward and impulsive behavior. Activation of D3 receptors by PPX was associated with dephosphorylated Akt, increasing activation of GSK3(3, and insertion of AMPAR subunits into the neuronal membrane. Enriched membrane AMPAR is associated with strengthening of glutamatergic synapses. Here, we extend these findings to a rat model of PD. We hypothesized that chronic administration of PPX to PD-like rats will alter the Akt/GSK3 R pathway in the NAc similar to acute PPX in both PD- and non-PD-like rats. We also hypothesized that effects seen in the dorsal striatum, a D2-rich brain region involved in motor function, will be greatest in PD-like rats. |
