Although most studies have focused on serotonin 5-HT1 receptor stimulation as an antidyskinetic strategy, targeting the serotonin transporter modulation of dopamine activity has been overlooked. Therefore, in the current study, selective serotonin reuptake inhibitors were tested for their ability to reduce l-DOPA- and apomorphine-induced dyskinesia. In Experiments 1 and 2, hemi-parkinsonian rats were primed with l-DOPA until stable dyskinesia developed. Rats

in Experiment 1 were administered the selective serotonin reuptake inhibitors paroxetine, citalopram or fluoxetine, followed by l-DOPA. Abnormal involuntary movements and forepaw adjusting steps were recorded to determine the effects of these compounds on dyskinesia and motor performance, respectively. Brains were collected on the final test day,

after which striatal and raphe monoamines were examined via high-performance MK-8669 in vivo liquid chromatography. In Experiment 2, dyskinesias were measured after selective serotonin reuptake inhibitors and apomorphine. Serotonin reuptake inhibitors dose-dependently attenuated l-DOPA- but not apomorphine-induced dyskinesia, and preserved l-DOPA efficacy. Neurochemically, serotonin transporter inhibition enhanced striatal and raphe serotonin levels and reduced its turnover, indicating a potential mechanism of action. The present learn more results support targeting serotonin transporters to improve Parkinson’s disease treatment and provide further evidence for the role of the serotonin system in l-DOPA’s effects. “
“Numerous studies have investigated the effects of lesions of the primary visual cortex (V1) on visual responses in neurons of the superficial layer of the superior colliculus (sSC),

which receives visual information from both the retina and V1. However, little is known about the changes in the local circuit dynamics of the sSC after receiving V1 lesions. Here, we show that surround inhibition of sSC neurons is transiently enhanced following V1 lesions in mice and that this enhancement may be attributed to alterations in the balance between excitatory and inhibitory inputs to sSC neurons. Extracellular recordings in vivo revealed that sSC neuronal responses to large visual stimuli were transiently Etofibrate reduced at about 1 week after visual cortical lesions compared with normal mice and that this reduction was partially recovered at about 1 month after the lesions. By using whole-cell patch-clamp recordings from sSC neurons in slice preparations obtained from mice that had received visual cortical lesions at 1 week prior to the recordings, we found cell type-dependent changes in the balance between excitation and inhibition. In non-GABAergic cells, inhibition predominated over excitation, whereas the excitation–inhibition balance did not change in GABAergic neurons.