Tyrosine hydroxylase-negative, dopaminergic neurons are targets for transmitter-depleting action of haloperidol in the snail brain.
1. The effects of long term administration of micromolar concentrations of the D2 antagonist haloperidol upon monoaminergic neurons in the snail Lymnaea stagnalis was investigated. 2. Treatment by bath application with 0.5-2.0 micromolar haloperidol, caused a significant, continuous depletion of dopamine levels in the nervous system as revealed by high performance liquid chromatography. 3. A transient depletion of serotonin was also observed, but DOPA and norepinephrine levels were unaffected. Similar depletion of dopamine was observed after the land snail, Achatina fulica, was injected with haloperidol on each of 4 consecutive days. 4. The depletion of dopamine as revealed with glyoxylate-induced fluorescence in Lymnaea appears to be restricted to a subpopulation of catecholaminergic neurons which are immuno-negative for tyrosine hydroxylase, the synthetic enzyme responsible for the conversion of tyrosine to DOPA. 5. The results thus demonstrate a depleting action of low micromolar doses of chronic haloperidol on specific subsets of dopaminergic neurons and a novel preparation for studying catecholaminergic mechanisms operating across the animal kingdom.
Sakharov
D A
DA
Institute of Developmental Biology, Russian Academy of Sciences, Moscow, Russia.
Voronezhskaya
E E
EE
Nezlin
L
L
Baker
M W
MW
Elekes
K
K
Croll
R P
RP
D000818:Animals; D004295:Dihydroxyphenylalanine / Q000032:analysis; D004298:Dopamine / Q000032:analysis*; D018492:Dopamine Antagonists / Q000494:pharmacology*; D065127:Dopamine D2 Receptor Antagonists; D017952:Ganglia, Invertebrate / Q000166:cytology*; D006220:Haloperidol / Q000494:pharmacology*; D008195:Lymnaea / Q000187:drug effects / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000032:analysis*; D009474:Neurons / Q000187:drug effects*; D009638:Norepinephrine / Q000032:analysis; D012701:Serotonin / Q000032:analysis; D012908:Snails / Q000187:drug effects* / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000032:analysis*
D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; D009419:Nerve Tissue Proteins; D012701:Serotonin; D004295:Dihydroxyphenylalanine; D014446:Tyrosine 3-Monooxygenase; D006220:Haloperidol; D004298:Dopamine; D009638:Norepinephrine