Antipsychotic drugs and dopamine-mediated responses in Aplysia neurons.
The effect of antipsychotic drugs was tested on responses to micro-electrophoretically applied dopamine, acetylcholine and 5-hydroxytryptamine in identified neurons of the marine gastropod Aplysia californica. Fluphenazine was able to depress the response to DA in concentration of 10 muM, with 100 muM DA-responses of many neurons were blocked completely. Thioridazine (10 and 100 muM) and haloperidol (50 muM) were also effective in depressing DA-responses, while the non-antipsychotic phenothiazines mepazine (10 and 100 muM) and promethazine (100 muM) had only a slight action on DA-receptors. ACh- and 5-HT-responses were slightly affected only by high concentrations after long lasting perfusion. The investigated drugs had no persistent or only an insignificant effect on resting membrane potential and amplitude of action potentials of the neurons. With haloperidol depolarizing afterpotentials leading to double discharges were observed in some neurons. In a few instances spontaneous EPSPs disappeared with the DA-response under the influence of anti-psychotic drugs. The results render a direct neurophysiological evidence for the blockade of DA-receptors by antipsychotic drugs in correspondence to their clinical efficacy and agree with data from clinical observations and obtained in neurochemical, behavioral and indirect neurophysiological experiments.
D000109:Acetylcholine / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005476:Fluphenazine / Q000494:pharmacology; D006220:Haloperidol / Q000494:pharmacology; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D008974:Mollusca; D009474:Neurons / Q000187:drug effects*; D010640:Phenothiazines / Q000494:pharmacology; D011954:Receptors, Dopamine / Q000187:drug effects*; D012701:Serotonin / Q000494:pharmacology; D013881:Thioridazine / Q000494:pharmacology
D014150:Antipsychotic Agents; D010640:Phenothiazines; D011954:Receptors, Dopamine; D012701:Serotonin; D006220:Haloperidol; D013881:Thioridazine; D000109:Acetylcholine; D005476:Fluphenazine