Serotonin neuron-dependent and -independent reduction of dyskinesia by 5-HT(1A) and 5-HT(1B) receptor agonists in the rat Parkinson model. Experimental neurology [Exp Neurol] Journal article

5-HT(1) receptor agonists have been shown to reduce abnormal involuntary movements (AIMs) in the rat and monkey models of L-DOPA-induced dyskinesia. Different mechanisms have been proposed to underlie this effect. Activation of pre-synaptic 5-HT(1) receptors has been suggested to inhibit dysregulated release of dopamine from the serotonin terminals, and thus, abnormal activation of striatal dopamine receptors. Activation of post-synaptic 5-HT(1) receptors expressed in non-serotonergic neurons in different brain areas, by contrast, have been shown to result in decreased glutamate and GABA release, which may also contribute to the antidyskinetic effect. To unveil the relative contribution of these mechanisms, we have investigated the effect of increasing doses of 5-HT(1A) and 5-HT(1B) receptor agonists on AIMs induced by either L-DOPA or apomorphine. In contrast to L-DOPA-induced AIMs, which was dampened already at low doses of 5-HT(1) agonists, reduction of apomorphine-induced AIMs required higher doses. Removal of the serotonin innervation suppressed L-DOPA-induced AIMs, but neither affected apomorphine-induced AIMs nor the inhibiting effect of 5-HT(1) agonists on AIMs induced by the dopamine direct agonist, suggesting that such effect is independent on activation of pre-synaptic 5-HT(1) receptors.

Experimental neurology [Exp Neurol]