Effects of dopamine and serotonin antagonist injections into the striatopallidal complex of asymptomatic MPTP-treated monkeys
The cardinal symptoms of Parkinson's disease (PD), akinesia, rigidity and tremor, are only observed when the striatal level of dopamine (DA) is decreased by 60–80%. It is likely that compensatory mechanisms during the early phase of DA depletion delay the appearance of motor symptoms. In a prev...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2012-10-01
|
| Series: | Neurobiology of Disease |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0969996112002100 |
| _version_ | 1818620448370327552 |
|---|---|
| author | Sara Neumane Stéphanie Mounayar Caroline Jan Justine Epinat Bénédicte Ballanger Nicolas Costes Jean Féger Stéphane Thobois Chantal François Véronique Sgambato-Faure Léon Tremblay |
| author_facet | Sara Neumane Stéphanie Mounayar Caroline Jan Justine Epinat Bénédicte Ballanger Nicolas Costes Jean Féger Stéphane Thobois Chantal François Véronique Sgambato-Faure Léon Tremblay |
| author_sort | Sara Neumane |
| collection | DOAJ |
| description | The cardinal symptoms of Parkinson's disease (PD), akinesia, rigidity and tremor, are only observed when the striatal level of dopamine (DA) is decreased by 60–80%. It is likely that compensatory mechanisms during the early phase of DA depletion delay the appearance of motor symptoms. In a previous study, we proposed a new PD monkey model with progressive MPTP intoxication. Monkeys developed all of the motor symptoms and then fully recovered despite a large DA cell loss in the substantia nigra (SN). Compensatory mechanisms certainly help to offset the dysfunction induced by the DA lesion, facilitating motor recovery in this model. Neurotransmitter measurements in the striatal sensorimotor and associative/limbic territories of these monkeys subsequently revealed that DA and serotonin (5-HT) could play a role in recovery mechanisms. To try to determine the involvement of these neurotransmitters in compensatory mechanisms, we performed local injections of DA and 5-HT antagonists (cis-flupenthixol and mianserin, respectively) into these two striatal territories and into the external segment of the globus pallidus (GPe). Injections were performed on monkeys that were in an asymptomatic state after motor recovery. Most parkinsonian motor symptoms reappeared in animals with DA antagonist injections either in sensorimotor, associative/limbic striatal territories or in the GPe. In contrast to the effects with DA antagonist, there were mild parkinsonian effects with 5-HT antagonist, especially after injections in sensorimotor territories of the striatum and the GPe. These results support a possible, but slight, involvement of 5-HT in compensatory mechanisms and highlight the possible participation of 5-HT in some behavioural disorders. Furthermore, these results support the notion that the residual DA in the different striatal territories and the GPe could be involved in important mechanisms of compensation in PD. |
| first_indexed | 2024-12-16T17:53:32Z |
| format | Article |
| id | doaj.art-25aa68c7a69d46babba1170f6e895b0e |
| institution | Directory Open Access Journal |
| issn | 1095-953X |
| language | English |
| last_indexed | 2024-12-16T17:53:32Z |
| publishDate | 2012-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Disease |
| spelling | doaj.art-25aa68c7a69d46babba1170f6e895b0e2022-12-21T22:22:14ZengElsevierNeurobiology of Disease1095-953X2012-10-014812739Effects of dopamine and serotonin antagonist injections into the striatopallidal complex of asymptomatic MPTP-treated monkeysSara Neumane0Stéphanie Mounayar1Caroline Jan2Justine Epinat3Bénédicte Ballanger4Nicolas Costes5Jean Féger6Stéphane Thobois7Chantal François8Véronique Sgambato-Faure9Léon Tremblay10Centre Nationale de la Recherche Scientifique, Centre de Neurosciences Cognitives, UMR 5229, Bron, France; Université Claude Bernard Lyon 1, Université de Lyon, Lyon, FranceInstitut National de la Santé et de la Recherche Médicale, UMR S975, Paris F-75013, France; Université Pierre et Marie Curie—Paris 6, Paris, FranceInstitut National de la Santé et de la Recherche Médicale, UMR S975, Paris F-75013, France; Université Pierre et Marie Curie—Paris 6, Paris, FranceCentre Nationale de la Recherche Scientifique, Centre de Neurosciences Cognitives, UMR 5229, Bron, France; Université Claude Bernard Lyon 1, Université de Lyon, Lyon, FranceCentre Nationale de la Recherche Scientifique, Centre de Neurosciences Cognitives, UMR 5229, Bron, France; Université Claude Bernard Lyon 1, Université de Lyon, Lyon, FranceCERMEP, Imagerie du vivant, F-69677, Bron, FranceInstitut National de la Santé et de la Recherche Médicale, UMR S975, Paris F-75013, France; Université Pierre et Marie Curie—Paris 6, Paris, FranceCentre Nationale de la Recherche Scientifique, Centre de Neurosciences Cognitives, UMR 5229, Bron, France; Université Claude Bernard Lyon 1, Université de Lyon, Lyon, FranceInstitut National de la Santé et de la Recherche Médicale, UMR S975, Paris F-75013, France; Université Pierre et Marie Curie—Paris 6, Paris, FranceCentre Nationale de la Recherche Scientifique, Centre de Neurosciences Cognitives, UMR 5229, Bron, France; Université Claude Bernard Lyon 1, Université de Lyon, Lyon, FranceCentre Nationale de la Recherche Scientifique, Centre de Neurosciences Cognitives, UMR 5229, Bron, France; Université Claude Bernard Lyon 1, Université de Lyon, Lyon, France; Corresponding author at: CNRS UMR5229, 67 Boulevard Pinel, 69675 Bron Cedex, France. Fax: +33 4 37 91 12 10.The cardinal symptoms of Parkinson's disease (PD), akinesia, rigidity and tremor, are only observed when the striatal level of dopamine (DA) is decreased by 60–80%. It is likely that compensatory mechanisms during the early phase of DA depletion delay the appearance of motor symptoms. In a previous study, we proposed a new PD monkey model with progressive MPTP intoxication. Monkeys developed all of the motor symptoms and then fully recovered despite a large DA cell loss in the substantia nigra (SN). Compensatory mechanisms certainly help to offset the dysfunction induced by the DA lesion, facilitating motor recovery in this model. Neurotransmitter measurements in the striatal sensorimotor and associative/limbic territories of these monkeys subsequently revealed that DA and serotonin (5-HT) could play a role in recovery mechanisms. To try to determine the involvement of these neurotransmitters in compensatory mechanisms, we performed local injections of DA and 5-HT antagonists (cis-flupenthixol and mianserin, respectively) into these two striatal territories and into the external segment of the globus pallidus (GPe). Injections were performed on monkeys that were in an asymptomatic state after motor recovery. Most parkinsonian motor symptoms reappeared in animals with DA antagonist injections either in sensorimotor, associative/limbic striatal territories or in the GPe. In contrast to the effects with DA antagonist, there were mild parkinsonian effects with 5-HT antagonist, especially after injections in sensorimotor territories of the striatum and the GPe. These results support a possible, but slight, involvement of 5-HT in compensatory mechanisms and highlight the possible participation of 5-HT in some behavioural disorders. Furthermore, these results support the notion that the residual DA in the different striatal territories and the GPe could be involved in important mechanisms of compensation in PD.http://www.sciencedirect.com/science/article/pii/S0969996112002100Parkinson's diseasePrimateMPTPDopamineSerotoninCompensatory mechanism |
| spellingShingle | Sara Neumane Stéphanie Mounayar Caroline Jan Justine Epinat Bénédicte Ballanger Nicolas Costes Jean Féger Stéphane Thobois Chantal François Véronique Sgambato-Faure Léon Tremblay Effects of dopamine and serotonin antagonist injections into the striatopallidal complex of asymptomatic MPTP-treated monkeys Neurobiology of Disease Parkinson's disease Primate MPTP Dopamine Serotonin Compensatory mechanism |
| title | Effects of dopamine and serotonin antagonist injections into the striatopallidal complex of asymptomatic MPTP-treated monkeys |
| title_full | Effects of dopamine and serotonin antagonist injections into the striatopallidal complex of asymptomatic MPTP-treated monkeys |
| title_fullStr | Effects of dopamine and serotonin antagonist injections into the striatopallidal complex of asymptomatic MPTP-treated monkeys |
| title_full_unstemmed | Effects of dopamine and serotonin antagonist injections into the striatopallidal complex of asymptomatic MPTP-treated monkeys |
| title_short | Effects of dopamine and serotonin antagonist injections into the striatopallidal complex of asymptomatic MPTP-treated monkeys |
| title_sort | effects of dopamine and serotonin antagonist injections into the striatopallidal complex of asymptomatic mptp treated monkeys |
| topic | Parkinson's disease Primate MPTP Dopamine Serotonin Compensatory mechanism |
| url | http://www.sciencedirect.com/science/article/pii/S0969996112002100 |
| work_keys_str_mv | AT saraneumane effectsofdopamineandserotoninantagonistinjectionsintothestriatopallidalcomplexofasymptomaticmptptreatedmonkeys AT stephaniemounayar effectsofdopamineandserotoninantagonistinjectionsintothestriatopallidalcomplexofasymptomaticmptptreatedmonkeys AT carolinejan effectsofdopamineandserotoninantagonistinjectionsintothestriatopallidalcomplexofasymptomaticmptptreatedmonkeys AT justineepinat effectsofdopamineandserotoninantagonistinjectionsintothestriatopallidalcomplexofasymptomaticmptptreatedmonkeys AT benedicteballanger effectsofdopamineandserotoninantagonistinjectionsintothestriatopallidalcomplexofasymptomaticmptptreatedmonkeys AT nicolascostes effectsofdopamineandserotoninantagonistinjectionsintothestriatopallidalcomplexofasymptomaticmptptreatedmonkeys AT jeanfeger effectsofdopamineandserotoninantagonistinjectionsintothestriatopallidalcomplexofasymptomaticmptptreatedmonkeys AT stephanethobois effectsofdopamineandserotoninantagonistinjectionsintothestriatopallidalcomplexofasymptomaticmptptreatedmonkeys AT chantalfrancois effectsofdopamineandserotoninantagonistinjectionsintothestriatopallidalcomplexofasymptomaticmptptreatedmonkeys AT veroniquesgambatofaure effectsofdopamineandserotoninantagonistinjectionsintothestriatopallidalcomplexofasymptomaticmptptreatedmonkeys AT leontremblay effectsofdopamineandserotoninantagonistinjectionsintothestriatopallidalcomplexofasymptomaticmptptreatedmonkeys |