Kynurenate blocks the acute effects of haloperidol on midbrain dopamine neurons recorded in vivo.
The acute effect of systemic administration of the antipsychotic drug haloperidol on the activity of midbrain dopamine (DA) neurons was investigated with extracellular single cell recording in the chloral hydrate anaesthetized male rat. DA cells in the zona compacta-substantia nigra (SN) and ventral tegmental area (VTA) were excited by low doses of haloperidol. This excitation, which included increased firing rate and burst firing, was no longer present after treatment with the excitatory amino acid (EAA) antagonist kynurenate (1 mumol ICV). Kynurenate alone profoundly regularized the activity and abolished burst firing in VTA-DA neurons, while SN-DA neuronal activity was unaffected by this treatment. Thus, VTA-DA neurons, but not SN neurons, appear to be dependent on a tonic EAA input for their normal varied, burst-firing activity. The antagonism of haloperidol-induced effects by kynurenate suggests that the acute excitatory action of haloperidol on midbrain DA neurons is executed via EAA neurons, in the case of the VTA probably via a corticofugal EAA pathway from the medial prefrontal cortex.
Tung
C S
CS
Department of Pharmacology, Karolinska Institute, Stockholm, Sweden.
Grenhoff
J
J
Svensson
T H
TH
D000200:Action Potentials / Q000187:drug effects; D000344:Afferent Pathways / Q000187:drug effects; D000818:Animals; D004298:Dopamine / Q000378:metabolism*; D006220:Haloperidol / Q000037:antagonists & inhibitors*; D007736:Kynurenic Acid / Q000494:pharmacology*; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects*; D013378:Substantia Nigra / Q000187:drug effects* / Q000378:metabolism; D013681:Tegmentum Mesencephali / Q000187:drug effects* / Q000378:metabolism
D011954:Receptors, Dopamine; D007736:Kynurenic Acid; D006220:Haloperidol; D004298:Dopamine