Manolo Carta, PhD

Tel: +46 46 222 05 55 Fax: + 46 46 222 05 59 E-mail: Manolo.Carta@med.lu.se

Research interests

During the last years my research interest has focused on the understanding of the mechanisms underlying the appearance of L-DOPA-induced dyskinesia in Parkinson´s disease patients using the rat 6-OHDA model. In fact, the ability of L-DOPA to relieve the motor impairments in Parkinson´s disease patients declines over time, and side effects, such as dyskinesias, appear, limiting the use of the drug in the advanced stage of disease. As the serotonin neurons have been shown to contribute to the conversion of L-DOPA to dopamine and release of the neurotransmitter in the synaptic cleft, we questioned about the role of this source of dopamine in the emergence of the side effect of L-DOPA. This is particularly relevant since the serotonin neurons lack a pre-synaptic feedback control mechanism for the release of dopamine, such as the dopamine transporter and D2 auto-receptor. Thus, we found that removal of the serotonin system by toxic lesion or pharmacological silencing of the serotonin neurons activity produces a complete abolishment of L-DOPA-induced dyskinesia (Carta et al, 2007).
Interestingly, we found a potent synergistic effect in the ability of combination of 5-HT1A and 5-HT1B receptor agonists to suppress L-DOPA-induced dyskinesia. This may have interesting clinical application, as targeting of the 5-HT1A receptors alone did not produce, in line with our results, significant reduction of dyskinesia in parkinsonian patients. Indeed, we have recently found that simultaneous activation of 5-HT1A and 5-HT1B receptors is able to suppress L-DOPA-induced dyskinesia also in the MPTP-treated monkey model of parkinson´s disease (Munoz et al, in press), rising the possibility for a similar mechanism for the appearance of L-DOPA-induced dyskinesia in primates. Dopamine release from the serotonin terminals appears therefore the main pre-synaptic determinant of L-DOPA-induced dyskinesia. We are currently aiming at clinical investigation of the efficacy of this pharmacological approach in dyskinetic parkinsonian patients.

• Curriculum Vitae
• Complete list of publications

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Neurobiology Unit, BMC A11
Department of Experimental Medical Science
Lund University
221 84 Lund, Sweden