Understanding the Functional Plasticity in Neural Networks of the Basal Ganglia in Cocaine Use Disorder: A Role for Allosteric Receptor-Receptor Interactions in A2A-D2 Heteroreceptor Complexes
Our hypothesis is that allosteric receptor-receptor interactions in homo- and heteroreceptor complexes may form the molecular basis of learning and memory. This principle is illustrated by showing how cocaine abuse can alter the adenosine A2AR-dopamine D2R heterocomplexes and their receptor-receptor...
Saved in:
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2016-01-01
|
| Series: | Neural Plasticity |
| Online Access: | http://dx.doi.org/10.1155/2016/4827268 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832557006950498304 |
|---|---|
| author | Dasiel O. Borroto-Escuela Karolina Wydra Julia Pintsuk Manuel Narvaez Fidel Corrales Magdalena Zaniewska Luigi F. Agnati Rafael Franco Sergio Tanganelli Luca Ferraro Malgorzata Filip Kjell Fuxe |
| author_facet | Dasiel O. Borroto-Escuela Karolina Wydra Julia Pintsuk Manuel Narvaez Fidel Corrales Magdalena Zaniewska Luigi F. Agnati Rafael Franco Sergio Tanganelli Luca Ferraro Malgorzata Filip Kjell Fuxe |
| author_sort | Dasiel O. Borroto-Escuela |
| collection | DOAJ |
| description | Our hypothesis is that allosteric receptor-receptor interactions in homo- and heteroreceptor complexes may form the molecular basis of learning and memory. This principle is illustrated by showing how cocaine abuse can alter the adenosine A2AR-dopamine D2R heterocomplexes and their receptor-receptor interactions and hereby induce neural plasticity in the basal ganglia. Studies with A2AR ligands using cocaine self-administration procedures indicate that antagonistic allosteric A2AR-D2R heterocomplexes of the ventral striatopallidal GABA antireward pathway play a significant role in reducing cocaine induced reward, motivation, and cocaine seeking. Anticocaine actions of A2AR agonists can also be produced at A2AR homocomplexes in these antireward neurons, actions in which are independent of D2R signaling. At the A2AR-D2R heterocomplex, they are dependent on the strength of the antagonistic allosteric A2AR-D2R interaction and the number of A2AR-D2R and A2AR-D2R-sigma1R heterocomplexes present in the ventral striatopallidal GABA neurons. It involves a differential cocaine-induced increase in sigma1Rs in the ventral versus the dorsal striatum. In contrast, the allosteric brake on the D2R protomer signaling in the A2AR-D2R heterocomplex of the dorsal striatopallidal GABA neurons is lost upon cocaine self-administration. This is potentially due to differences in composition and allosteric plasticity of these complexes versus those in the ventral striatopallidal neurons. |
| format | Article |
| id | doaj-art-21faf16683ef49559aa3f5ce9d99b257 |
| institution | Kabale University |
| issn | 2090-5904 1687-5443 |
| language | English |
| publishDate | 2016-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Neural Plasticity |
| spelling | doaj-art-21faf16683ef49559aa3f5ce9d99b2572025-02-03T05:43:49ZengWileyNeural Plasticity2090-59041687-54432016-01-01201610.1155/2016/48272684827268Understanding the Functional Plasticity in Neural Networks of the Basal Ganglia in Cocaine Use Disorder: A Role for Allosteric Receptor-Receptor Interactions in A2A-D2 Heteroreceptor ComplexesDasiel O. Borroto-Escuela0Karolina Wydra1Julia Pintsuk2Manuel Narvaez3Fidel Corrales4Magdalena Zaniewska5Luigi F. Agnati6Rafael Franco7Sergio Tanganelli8Luca Ferraro9Malgorzata Filip10Kjell Fuxe11Department of Neuroscience, Karolinska Institutet, Retzius väg 8. 17177 Stockholm, SwedenLaboratory of Drug Addiction Pharmacology, Institute of Pharmacology, Polish Academy of Sciences, 12 Smetna Street, PL-31-343 Kraków, PolandDepartment of Neuroscience, Karolinska Institutet, Retzius väg 8. 17177 Stockholm, SwedenUniversidad de Málaga, Instituto de Investigación Biomédica de Málaga, Facultad de Medicina, Málaga, SpainObservatorio Cubanos de Neurociencias, Grupo Bohío-Estudio, Yaguajay, CubaLaboratory of Drug Addiction Pharmacology, Institute of Pharmacology, Polish Academy of Sciences, 12 Smetna Street, PL-31-343 Kraków, PolandDepartment of Neuroscience, Karolinska Institutet, Retzius väg 8. 17177 Stockholm, SwedenDepartament de Bioquímica i Biomedicina Molecular, Facultat de Biologia, Universitat de Barcelona, Barcelona, SpainDepartment of Life Sciences and Biotechnology, University of Ferrara, Ferrara, ItalyDepartment of Life Sciences and Biotechnology, University of Ferrara, Ferrara, ItalyLaboratory of Drug Addiction Pharmacology, Institute of Pharmacology, Polish Academy of Sciences, 12 Smetna Street, PL-31-343 Kraków, PolandDepartment of Neuroscience, Karolinska Institutet, Retzius väg 8. 17177 Stockholm, SwedenOur hypothesis is that allosteric receptor-receptor interactions in homo- and heteroreceptor complexes may form the molecular basis of learning and memory. This principle is illustrated by showing how cocaine abuse can alter the adenosine A2AR-dopamine D2R heterocomplexes and their receptor-receptor interactions and hereby induce neural plasticity in the basal ganglia. Studies with A2AR ligands using cocaine self-administration procedures indicate that antagonistic allosteric A2AR-D2R heterocomplexes of the ventral striatopallidal GABA antireward pathway play a significant role in reducing cocaine induced reward, motivation, and cocaine seeking. Anticocaine actions of A2AR agonists can also be produced at A2AR homocomplexes in these antireward neurons, actions in which are independent of D2R signaling. At the A2AR-D2R heterocomplex, they are dependent on the strength of the antagonistic allosteric A2AR-D2R interaction and the number of A2AR-D2R and A2AR-D2R-sigma1R heterocomplexes present in the ventral striatopallidal GABA neurons. It involves a differential cocaine-induced increase in sigma1Rs in the ventral versus the dorsal striatum. In contrast, the allosteric brake on the D2R protomer signaling in the A2AR-D2R heterocomplex of the dorsal striatopallidal GABA neurons is lost upon cocaine self-administration. This is potentially due to differences in composition and allosteric plasticity of these complexes versus those in the ventral striatopallidal neurons.http://dx.doi.org/10.1155/2016/4827268 |
| spellingShingle | Dasiel O. Borroto-Escuela Karolina Wydra Julia Pintsuk Manuel Narvaez Fidel Corrales Magdalena Zaniewska Luigi F. Agnati Rafael Franco Sergio Tanganelli Luca Ferraro Malgorzata Filip Kjell Fuxe Understanding the Functional Plasticity in Neural Networks of the Basal Ganglia in Cocaine Use Disorder: A Role for Allosteric Receptor-Receptor Interactions in A2A-D2 Heteroreceptor Complexes Neural Plasticity |
| title | Understanding the Functional Plasticity in Neural Networks of the Basal Ganglia in Cocaine Use Disorder: A Role for Allosteric Receptor-Receptor Interactions in A2A-D2 Heteroreceptor Complexes |
| title_full | Understanding the Functional Plasticity in Neural Networks of the Basal Ganglia in Cocaine Use Disorder: A Role for Allosteric Receptor-Receptor Interactions in A2A-D2 Heteroreceptor Complexes |
| title_fullStr | Understanding the Functional Plasticity in Neural Networks of the Basal Ganglia in Cocaine Use Disorder: A Role for Allosteric Receptor-Receptor Interactions in A2A-D2 Heteroreceptor Complexes |
| title_full_unstemmed | Understanding the Functional Plasticity in Neural Networks of the Basal Ganglia in Cocaine Use Disorder: A Role for Allosteric Receptor-Receptor Interactions in A2A-D2 Heteroreceptor Complexes |
| title_short | Understanding the Functional Plasticity in Neural Networks of the Basal Ganglia in Cocaine Use Disorder: A Role for Allosteric Receptor-Receptor Interactions in A2A-D2 Heteroreceptor Complexes |
| title_sort | understanding the functional plasticity in neural networks of the basal ganglia in cocaine use disorder a role for allosteric receptor receptor interactions in a2a d2 heteroreceptor complexes |
| url | http://dx.doi.org/10.1155/2016/4827268 |
| work_keys_str_mv | AT dasieloborrotoescuela understandingthefunctionalplasticityinneuralnetworksofthebasalgangliaincocaineusedisorderaroleforallostericreceptorreceptorinteractionsina2ad2heteroreceptorcomplexes AT karolinawydra understandingthefunctionalplasticityinneuralnetworksofthebasalgangliaincocaineusedisorderaroleforallostericreceptorreceptorinteractionsina2ad2heteroreceptorcomplexes AT juliapintsuk understandingthefunctionalplasticityinneuralnetworksofthebasalgangliaincocaineusedisorderaroleforallostericreceptorreceptorinteractionsina2ad2heteroreceptorcomplexes AT manuelnarvaez understandingthefunctionalplasticityinneuralnetworksofthebasalgangliaincocaineusedisorderaroleforallostericreceptorreceptorinteractionsina2ad2heteroreceptorcomplexes AT fidelcorrales understandingthefunctionalplasticityinneuralnetworksofthebasalgangliaincocaineusedisorderaroleforallostericreceptorreceptorinteractionsina2ad2heteroreceptorcomplexes AT magdalenazaniewska understandingthefunctionalplasticityinneuralnetworksofthebasalgangliaincocaineusedisorderaroleforallostericreceptorreceptorinteractionsina2ad2heteroreceptorcomplexes AT luigifagnati understandingthefunctionalplasticityinneuralnetworksofthebasalgangliaincocaineusedisorderaroleforallostericreceptorreceptorinteractionsina2ad2heteroreceptorcomplexes AT rafaelfranco understandingthefunctionalplasticityinneuralnetworksofthebasalgangliaincocaineusedisorderaroleforallostericreceptorreceptorinteractionsina2ad2heteroreceptorcomplexes AT sergiotanganelli understandingthefunctionalplasticityinneuralnetworksofthebasalgangliaincocaineusedisorderaroleforallostericreceptorreceptorinteractionsina2ad2heteroreceptorcomplexes AT lucaferraro understandingthefunctionalplasticityinneuralnetworksofthebasalgangliaincocaineusedisorderaroleforallostericreceptorreceptorinteractionsina2ad2heteroreceptorcomplexes AT malgorzatafilip understandingthefunctionalplasticityinneuralnetworksofthebasalgangliaincocaineusedisorderaroleforallostericreceptorreceptorinteractionsina2ad2heteroreceptorcomplexes AT kjellfuxe understandingthefunctionalplasticityinneuralnetworksofthebasalgangliaincocaineusedisorderaroleforallostericreceptorreceptorinteractionsina2ad2heteroreceptorcomplexes |