The dopaminergic stabilizer pridopidine demonstrates state-dependent effects on 
locomotor activity, counteracting both hypo- and hyperactivity in rats. 
Pridopidine has been shown to display both functional dopamine D2 receptor 
antagonist properties and increase in biomarkers associated with NMDA-mediated 
glutamate transmission in the frontal cortex. To further characterise the 
effects of pridopidine on prefrontal cortex (PFC) neurons, a series of in vivo 
electrophysiological studies were performed in urethane-anaesthetised rats. 
Pridopidine, administered at doses from 10 to 60 mg/kg (i.v.), dose dependently 
increased pyramidal cell firing in the majority of the neurons tested. 
Pridopidine induced a significant increase of 162 % in mean firing activity of 
PFC neurons, versus initial basal firing activity as the cumulative dose of 30 
mg/kg, i.v., was administered. This enhancement of activity was due to increased 
firing frequency of already spontaneously active neurons, rather than an 
increase in population activity. The increase was partially reversed or 
prevented by a sub-threshold dose of the dopamine D1 receptor antagonist 
SCH23390 (0.5 mg/kg, i.v.). Microiontophoretic application of pridopidine had 
only moderate activating effects. The selective dopamine D1 receptor agonist 
A-68930 also had limited effects when administered by microiontophoretic 
application, but exerted a dose dependent (0.2-3 mg/kg, i.v.) activation of 
firing in the majority of neurons tested (10/16). However, inhibition of firing 
by systemic administration of A-68930 was also observed in a subgroup of neurons 
(6/16). Both activation and inhibition of firing induced by systemic 
administration of A-68930 were reversed by the systemic administration of 
SCH23390. The present data suggests that pridopidine enhances pyramidal cell 
firing via an indirect dopamine D1 receptor-mediated mechanism. These effects of 
pridopidine may serve to strengthen the cortico-striatal communication and to 
improve motor control in Huntington's disease for which pridopidine is currently 
in development.