Interactions of antipsychotic drugs with norepinephrine and cerebellar neuronal circuitry: implications for the psychobiology of psychosis.
Using the rat cerebellar Purkinje cell as a model neuronal system, the effects of norepinephrine and fluphenazine, an antipsychotic drug, are examined. Fluphenazine is shown to be a potent, specific antagonist of the norepinephrine-mediated inhibition of Purkinje cell discharge. Norepinephrine, despite its inhibitory action on spontaneous firing of the Purkinje cell, increases its responsiveness to afferent synaptic pathways. These data thus imply that norepinephrine may increase the brain's sensitivity to incoming information, and that antipsychotic drugs interfere with this effect. A role for norepinephrine, as well as dopamine, in the genesis of psychosis is suggested on the basis of their mutual antagonism by anti-psychotic drugs. The facilatory effects of NE on neuronal information-processing are used to predict a possible participation of NE in the perceptual difficulties noted in psychosis.
D000200:Action Potentials; D000344:Afferent Pathways / Q000187:drug effects; D000818:Animals; D002531:Cerebellum / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004336:Drug Antagonism; D004347:Drug Interactions; D005475:Flupenthixol / Q000494:pharmacology; D005476:Fluphenazine / Q000494:pharmacology*; D006801:Humans; D007536:Isomerism; D008297:Male; D008959:Models, Neurological; D009433:Neural Inhibition / Q000187:drug effects; D009474:Neurons / Q000187:drug effects; D009638:Norepinephrine / Q000494:pharmacology*; D011398:Promethazine / Q000494:pharmacology; D011618:Psychotic Disorders / Q000209:etiology*; D011689:Purkinje Cells; D051381:Rats
D005475:Flupenthixol; D011398:Promethazine; D005476:Fluphenazine; D009638:Norepinephrine