Droperidol suppresses spontaneous electrical activity in neurons cultured from ventral midbrain. Implications for neuroleptanesthesia.
Droperidol is used in anesthesia as an antiemetic and as a component in neuroleptanalgesia. Its mechanism of action is thought to involve dopamine receptor blockade in the brain. The electrophysiological consequences associated with this action however, have not been elucidated. In this study we demonstrate a dose-dependent electrophysiological response to droperidol in central nervous system (CNS) neurons that express dopamine receptors that is absent in CNS neurons that do not express dopamine receptors. Primary dissociated cell (PDC) cultures were prepared from embryonal tissue dissected from ventral mesencephalon (VM) and spinal cord (SC). VM neurons were used to investigate the electrophysiological action of droperidol, a dopamine receptor antagonist, since these cultures contain neurons having dopamine receptors on their surface. SC neurons were used as a control as they do not express dopamine receptors. Some dopamine receptors are on dopaminergic neurons and therefore are called autoreceptors, while others are on nondopaminergic neurons, such as GABA producing (GABAergic) neurons. All neurons in both PDC cultures were spontaneously active. The percentage of neurons which spontaneously generated action potentials was reduced in a dose-dependent manner by droperidol (1 nM-10 microM) only in PDC cultures of VM. Exposure to droperidol had no effect on neurons from PDC cultures of SC which lack dopamine receptors. Our results suggest that droperidol modulates the electrophysiological properties of VM neurons with dopamine receptors possibly through facilitation of inhibitory interneurons. The reduced activity of VM neurons might contribute to the antiemetic and/or anesthetic activity of droperidol, since the concentrations of droperidol used in this study are at clinically relevant concentrations.
Heyer
E J
EJ
Departments of Anesthesiology and Neurology, Columbia University, 630 West 168th Street, New York, NY, USA.
Flood
P
P
D000200:Action Potentials / Q000187:drug effects* / Q000502:physiology*; D000818:Animals; D002478:Cells, Cultured; D004298:Dopamine / Q000378:metabolism; D018492:Dopamine Antagonists / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004329:Droperidol / Q000494:pharmacology*; D005333:Fetus; D008636:Mesencephalon / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D051379:Mice; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000187:drug effects / Q000378:metabolism; D013116:Spinal Cord / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
D018492:Dopamine Antagonists; D017448:Receptors, Dopamine D2; D004329:Droperidol; D004298:Dopamine