title: Serotonin neuron-dependent and -independent reduction of dyskinesia by 5-HT1A and 5-HT1B receptor agonists in the rat Parkinson model.
abstract: 5-HT1 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-HT1 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-HT1 receptors expressed in non-serotonergic neurons in different brain areas, by contrast, has 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-HT1A and 5-HT1B receptor agonists on AIMs induced by either L-DOPA or apomorphine. In contrast to L-DOPA-induced AIMs, which were dampened already at low doses of 5-HT1 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-HT1 agonists on AIMs induced by the direct dopamine agonist, suggesting that such effect is independent on activation of pre-synaptic 5-HT1 receptors.
authors.affiliation: Neurobiology Unit, Wallenberg Neuroscience Center, Department of Experimental Medical Science, Lund University, Lund, Sweden.
authors.forename: Ana
authors.initials: A
authors.lastname: Muñoz
authors.forename: Thomas
authors.initials: T
authors.lastname: Carlsson
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Tronci
authors.forename: Deniz
authors.initials: D
authors.lastname: Kirik
authors.forename: Anders
authors.initials: A
authors.lastname: Björklund
authors.forename: Manolo
authors.initials: M
authors.lastname: Carta
mesh_terms: D000818:Animals; D001058:Apomorphine / Q000009:adverse effects; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D004195:Disease Models, Animal; D018491:Dopamine Agonists / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D004409:Dyskinesia, Drug-Induced / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D005260:Female; D007980:Levodopa / Q000009:adverse effects; D010300:Parkinson Disease / Q000188:drug therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism; D044302:Receptor, Serotonin, 5-HT1B / Q000378:metabolism; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism*; D058825:Serotonin 5-HT1 Receptor Agonists; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*
chemical_list: D018491:Dopamine Agonists; D044302:Receptor, Serotonin, 5-HT1B; D011985:Receptors, Serotonin; D058825:Serotonin 5-HT1 Receptor Agonists; D017366:Serotonin Receptor Agonists; D044282:Receptor, Serotonin, 5-HT1A; D012701:Serotonin; D007980:Levodopa; D001058:Apomorphine