Modulation of serotonergic transmission by eltoprazine in L-DOPA-induced dyskinesia: Behavioral, molecular, and synaptic mechanisms

The present study demonstrates that activation of 5-HT1A/1B receptors reduces AIMs via the restoration of Long-Term Potentiation (LTP) and synaptic depotentiation in a sub-set of striatal spiny projection neurons (SPNs). This recovery is associated with the normalization of D1 receptor-dependent cAMP/PKA and ERK/mTORC signaling pathways, and the recovery of NMDA receptor subunits balance, indicating these events as key elements in AIMs induction. Moreover, we analyzed whether the manipulation of the serotonergic system might affect motor behavior and cognitive performances. We found that a defect in locomotor activity in parkinsonian and L-DOPA-treated rats was reversed by eltoprazine treatment. Conversely, the impairment in the striatal-dependent learning was found exacerbated in L-DOPA-treated rats and eltoprazine failed to recover it.