TY - JOUR
T1 - Evidence for a substrate of neuronal plasticity based on pre- and postsynaptic neurotensin-dopamine receptor interactions in the neostriatum
AU - Fuxe, Kjell
AU - O'Connor, William T.
AU - Antonelli, Tiziana
AU - Osborne, Peter G.
AU - Tanganelli, Sergio
AU - Agnati, Luigi F.
AU - Ungerstedt, Urban
PY - 1992
Y1 - 1992
N2 - The major mechanism underlying the neuroleptic action of the tridecapeptide neurotensin (NT) appears to be an interaction with dopamine receptor mechanisms based on biochemical binding and behavioral experiments. In vivo microdialysis was used in conscious rats to investigate the effects of local perfusion with NT on the sensitivity of striatal dopamine D1 and D2 receptors for their selective agonists by monitoring extracellular dopamine, 3,4-dihydroxyphenylacetic acid, homovanilic acid, and γ-aminobutyric acid levels in the awake unrestrained male rat. Perfusion with NT (10 nM) counteracted the inhibitory effects of the dopamine D2 agonist pergolide (500 nM) on extracellular levels of dopamine and γ-aminobutyric acid. In contrast, NT (10 nM) significantly enhanced the reduction of extracellular striatal levels of dopamine after perfusion with the D1 agonist SKF 38393 (5 μM), and this combined treatment also resulted in a significant increase in the extracellular striatal levels of γ-aminobutyric acid. These results provide in vivo evidence that NT regulates central dopamine transmission by reducing pre- and postsynaptic dopamine D2 and enhancing D1 receptor sensitivity possibly through an antagonistic NT receptor-D2 receptor interaction. This heteroregulation has the potential to substantially increase the plasticity within the dopamine synapse. (.
AB - The major mechanism underlying the neuroleptic action of the tridecapeptide neurotensin (NT) appears to be an interaction with dopamine receptor mechanisms based on biochemical binding and behavioral experiments. In vivo microdialysis was used in conscious rats to investigate the effects of local perfusion with NT on the sensitivity of striatal dopamine D1 and D2 receptors for their selective agonists by monitoring extracellular dopamine, 3,4-dihydroxyphenylacetic acid, homovanilic acid, and γ-aminobutyric acid levels in the awake unrestrained male rat. Perfusion with NT (10 nM) counteracted the inhibitory effects of the dopamine D2 agonist pergolide (500 nM) on extracellular levels of dopamine and γ-aminobutyric acid. In contrast, NT (10 nM) significantly enhanced the reduction of extracellular striatal levels of dopamine after perfusion with the D1 agonist SKF 38393 (5 μM), and this combined treatment also resulted in a significant increase in the extracellular striatal levels of γ-aminobutyric acid. These results provide in vivo evidence that NT regulates central dopamine transmission by reducing pre- and postsynaptic dopamine D2 and enhancing D1 receptor sensitivity possibly through an antagonistic NT receptor-D2 receptor interaction. This heteroregulation has the potential to substantially increase the plasticity within the dopamine synapse. (.
KW - D receptors
KW - Dopamine release
KW - Microdialysis
KW - γ-aminobutyric acid release
UR - http://www.scopus.com/inward/record.url?scp=0026773440&partnerID=8YFLogxK
U2 - 10.1073/pnas.89.12.5591
DO - 10.1073/pnas.89.12.5591
M3 - Article
C2 - 1535159
AN - SCOPUS:0026773440
SN - 0027-8424
VL - 89
SP - 5591
EP - 5595
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 12
ER -