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Involvement of the direct striatonigral pathway in levodopa‐induced sensitization in 6‐hydroxydopamine‐lesioned rats
Author(s) -
Bordet Régis,
Ridray Sophie,
Schwartz JeanCharles,
Sokoloff Pierre
Publication year - 2000
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1046/j.1460-9568.2000.00089.x
Subject(s) - dynorphin , hydroxydopamine , sch 23390 , chemistry , levodopa , sensitization , dopamine receptor d3 , pharmacology , substantia nigra , endocrinology , medicine , dopamine , receptor , antagonist , dopamine receptor d2 , parkinson's disease , biology , neuroscience , opioid , dopaminergic , biochemistry , opioid peptide , disease
Induction of dopamine D 3 receptor gene expression in 6‐hydroxydopamine‐lesioned rats by repeated administration of levodopa had been suggested to be responsible for behavioural sensitization developing in these animals. Using double in situ hybridization techniques, we show that D 3 receptor mRNA induction after repeated administration of levodopa took place mainly in dynorphin/substance P‐expressing neurons of the direct striatonigral pathway. In agreement, induction of D 3 receptor binding sites was evidenced, using 7‐[ 3 H]hydroxy‐N,N‐di‐propyl‐2‐aminotetralin ([ 3 H]7‐OH‐DPAT), in substantia nigra pars reticulata, the projection area of the direct nigrostriatonigral pathway. Changes in D 3 receptor binding and behavioural sensitization during intermittent administration of levodopa paralleled changes in prodynorphin/preprotachykinin rather than preproenkephalin/prodynorphin and preproenkephalin/preprotachykinin mRNA ratios. Behavioural sensitization, induction of D 3 receptor binding and changes in prodynorphin/preprotachykinin ratio were all prevented together when levodopa was continuously delivered or intermittently delivered in combination with r ‐(+)‐7‐chloro‐8‐hydroxy‐3‐methyl‐1‐phenyl‐2,3,4,5‐tetrahydro‐1H‐3‐benzazepine (SCH 23390), a selective D 1 receptor antagonist. Our results indicate that functional changes of the direct striatal output pathway, possibly through an interaction between D 1 and D 3 receptors at the level of terminals in the substantia nigra pars reticulata, are important for the development of behavioural sensitization.