Haloperidol-induced reduction of nigral substance P-like immunoreactivity: a probe for the interactions between dopamine and substance P neuronal systems.
Protracted blockade of dopamine receptors by haloperidol has been shown to cause a reduction in nigral content of substance P-like immunoreactivity (SPLI). This pharmacological effect is used to study the mechanisms whereby the dopaminergic and substance P systems interact. Data presented in this paper suggest that 1) blockade of dopamine postsynaptic receptors alters nigral SPLI levels associated with the substance P striatal-nigral loop, 2) destruction of the nigral-striatal dopaminergic pathway results in changes in nigral content of SPLI similar to that induced by haloperidol, 3) several weeks after nigral-striatal lesions, compensatory mechanisms mediate a return of nigral SPLI content to control levels and 4) 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. The data support a dynamic role for striatal-nigral substance P fibers in the extrapyramidal circuitry and suggest that his pathway must be accounted for when studying the interactions of transmitter systems within this locomotor center.
D000818:Animals; D003342:Corpus Striatum / Q000502:physiology; D004298:Dopamine / Q000502:physiology*; D018492:Dopamine Antagonists; D006220:Haloperidol / Q000494:pharmacology*; D008297:Male; D009474:Neurons / Q000502:physiology*; D051381:Rats; D013373:Substance P / Q000378:metabolism* / Q000502:physiology; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology
D018492:Dopamine Antagonists; D013373:Substance P; D006220:Haloperidol; D004298:Dopamine