HALOPERIDOL-INDUCED REDUCTION OF NIGRAL SUBSTANCE-P-LIKE IMMUNOREACTIVITY - A PROBE FOR THE INTERACTIONS BETWEEN DOPAMINE AND SUBSTANCE-P NEURONAL SYSTEMS

  • 1 January 1981
    • journal article
    • research article
    • Vol. 218  (2) , 568-574
Abstract
Protracted blockade of dopamine receptors by haloperidol causes a reduction in nigral content of substance P-like immunoreactivity (SPLI). This pharmacological effect was used in rats to study the mechanisms whereby dopaminergic and substance P systems interact. Blockade of dopamine postsynaptic receptors alters nigral SPLI levels associated with the substance P striatal-nigral loop. Destruction of the nigral-striatal dopaminergic pathway results in changes in nigral content of SPLI similar to that induced by haloperidol. Several weeks after nigral-striatal lesions, compensatory mechanisms mediate a return of nigral SPLI content to control levels and substance P striatal-nigral circuits continue to respond to dopaminergic input after kainic acid lesions in the anterior striatum, whereas properly placed mechanical striatal-nigral lesions appear to be effective in preventing this interaction. A dynamic role for striatal-nigral substance P fibers in the extrapyramidal circuitry is suggested. This pathway should be accounted for when studying interactions of transmitter systems within this locomotor center.

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