A serotonin 5-HT1A receptor agonist prevents behavioral sensitization to L-DOPA in a rodent model of Parkinson's disease.
Marked fluctuation of dopamine concentration in the striatum following long-term L-DOPA administration contributes to the development of L-DOPA-induced motor complications including L-DOPA-induced dyskinesias and wearing-off in patients with Parkinson's disease. We have shown that pretreatment with 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), a 5-HT1A (5-hydroxytryptamine) receptor agonist, alleviates fluctuation of dopamine levels in the dopamine-denervated striatum of 6-hydroxydopamine-lesioned (hemiparkinsonian) rats after L-DOPA treatment. To determine whether co-administration of 8-OH-DPAT with L-DOPA prevents L-DOPA-induced motor complications, we examined rotation behavior and levels of messenger RNAs coding for dynorphin and glutamic acid decarboxylase in the striatum of 6-hydroxydopamine-lesioned rats treated with L-DOPA alone or L-DOPA + 8-OH-DPAT, twice daily, for 2 weeks. Co-administration of 8-OH-DPAT inhibited an increase of rotation behavior to L-DOPA and L-DOPA-induced increases in levels of messenger RNAs coding for dynorphin and glutamic acid decarboxylase in the dopamine-denervated striatum, both of which are established indices of L-DOPA-induced motor complications. These results suggest that pharmaceutical products that stimulate 5-HT1A receptors could prove useful in prevention of the development of L-DOPA-induced motor complications in patients with Parkinson's disease.
Tomiyama
Masahiko
M
Department of Neurological Science, Institute of Brain Science, Hirosaki University School of Medicine, Hirosaki 036-8562, Japan.
Kimura
Tamaki
T
Maeda
Tetsuya
T
Kannari
Kazuya
K
Matsunaga
Muneo
M
Baba
Masayuki
M
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000008:administration & dosage*; D000818:Animals; D000978:Antiparkinson Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001522:Behavior, Animal; D003342:Corpus Striatum; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D004399:Dynorphins / Q000187:drug effects / Q000378:metabolism; D004409:Dyskinesia, Drug-Induced / Q000517:prevention & control*; D005260:Female; D005968:Glutamate Decarboxylase / Q000187:drug effects / Q000378:metabolism; D017403:In Situ Hybridization; D007980:Levodopa / Q000008:administration & dosage* / Q000009:adverse effects; D010300:Parkinson Disease / Q000188:drug therapy*; D051381:Rats; D017208:Rats, Wistar; D017366:Serotonin Receptor Agonists / Q000008:administration & dosage*
D000978:Antiparkinson Agents; D017366:Serotonin Receptor Agonists; D007980:Levodopa; D004399:Dynorphins; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D005968:Glutamate Decarboxylase