Dopamine D2 receptors exert tonic regulation over discrete neurotensin systems of the rat brain.
Blockade of dopamine D2 receptors with either the selective antagonist, sulpiride, or the non-selective antagonist, haloperidol, induces 2- to 3-fold increases in the content of neurotensin-like immunoreactivity in the striatum and the nucleus accumbens of the rat brain. Quantitatively similar increases were also observed (a) in the striatum following selective degeneration of more than 85% of the nigrostriatal dopamine pathway with 6-hydroxydopamine and (b) in both the striatum and the nucleus accumbens after non-selective depletion of brain dopamine using reserpine plus alpha-methyl-p-tyrosine. Interestingly, treatment of animals with sulpiride or haloperidol, following the depletion of dopamine by either 6-hydroxydopamine or reserpine plus alpha-methyl-p-tyrosine, did not add to the elevation in neurotensin content of either structure caused by the dopamine depletion alone. These data suggest that an intact dopamine system is required for the neuroleptics to exert their effects on individual neurotensin systems. In addition, the same mechanism appears to underlie the responses of the neurotensin pathways to treatments with the neuroleptics or dopamine-depleting drugs. A likely explanation for the effects of neuroleptics and dopamine-depleting drugs is that they eliminate tonic activity on D2 receptors by basally released dopamine in the striatum and the nucleus accumbens. Supportive evidence for this hypothesis is that concurrent administration of the D2 receptor agonist, LY 171555, with reserpine, completely blocked the effects of reserpine-induced dopamine depletion on neurotensin systems of the striatum and the nucleus accumbens.
Merchant
K M
KM
Department of Pharmacology and Toxicology, University of Utah, Salt Lake City 84112.
Bush
L G
LG
Gibb
J W
JW
Hanson
G R
GR
D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D006220:Haloperidol / Q000494:pharmacology*; D006892:Hydroxydopamines; D008297:Male; D009496:Neurotensin / Q000378:metabolism*; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism*; D016627:Oxidopamine; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000502:physiology*; D017448:Receptors, Dopamine D2; D012110:Reserpine / Q000494:pharmacology; D012686:Septal Nuclei / Q000378:metabolism*; D013469:Sulpiride / Q000494:pharmacology*
D006892:Hydroxydopamines; D011954:Receptors, Dopamine; D017448:Receptors, Dopamine D2; D009496:Neurotensin; D013469:Sulpiride; D012110:Reserpine; D016627:Oxidopamine; D006220:Haloperidol