Modulation by endogenous dopamine of the release of acetylcholine in the caudate nucleus of the rabbit.
Slices of the caudate nucleus of rabbits were preincubated with 3H-choline and then superfused. Stimulation by electrical pulses at 3 Hz or by 25 mmol/l potassium elicited an increase in tritium outflow which was calcium-dependent and, in the case of electrical stimulation, tetrodotoxin-sensitive. The dopamine receptor agonist apomorphine (0.01-1 mumol/l) decreased, whereas the antagonist haloperidol increased the electrically evoked overflow of tritium. Nomifensine and cocaine, used at concentrations known to inhibit the re-uptake of dopamine, also reduced the evoked overflow of tritium, and this reduction was antagonized by haloperidol. Combined pretreatment with reserpine and alpha-methyltyrosine methylester (alpha-MT), which lowered dopamine levels by 99.5%, increased the electrically evoked overflow, as did bretylium which is shown here to block action potential-induced release of dopamine. The facilitation by haloperidol and bretylium as well as the inhibition by nomifensine and cocaine were diminished or abolished after pretreatment with reserpine plus alpha-MT. Apomorphine decreased, and haloperidol increased, the potassium-evoked overflow of tritium; the effects were not changed by tetrodotoxin. The results indicate that the striatal dopamine receptors which, when activated, depress the release of acetylcholine, are akin to the D-2 type. Endogenous dopamine also acts on the receptors as shown by several manipulations with known effects on dopaminergic transmission. A large fraction of these dopamine receptors may be located on the cholinergic axon terminals.
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D001950:Bretylium Tosylate / Q000494:pharmacology; D002421:Caudate Nucleus / Q000378:metabolism*; D003042:Cocaine / Q000494:pharmacology; D004298:Dopamine / Q000502:physiology*; D004558:Electric Stimulation; D006220:Haloperidol / Q000494:pharmacology; D009627:Nomifensine / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D011817:Rabbits
D009627:Nomifensine; D001950:Bretylium Tosylate; D003042:Cocaine; D006220:Haloperidol; D001058:Apomorphine; D000109:Acetylcholine; D011188:Potassium; D004298:Dopamine