1. Acute and subchronic PCP attenuate D2 autoreceptor signaling in substantia nigra dopamine neurons
- Author
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Elisabeth Piccart, Christopher W. Tschumi, and Michael J. Beckstead
- Subjects
Male ,Patch-Clamp Techniques ,Dopamine ,Action Potentials ,Phencyclidine ,Substantia nigra ,Pharmacology ,In Vitro Techniques ,Kynurenic Acid ,Article ,Drug Administration Schedule ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Dopamine receptor D2 ,medicine ,Animals ,Pharmacology (medical) ,Biological Psychiatry ,Dopamine transporter ,biology ,Dose-Response Relationship, Drug ,Chemistry ,Receptors, Dopamine D2 ,Dopaminergic Neurons ,Dopaminergic ,Iontophoresis ,Electric Stimulation ,030227 psychiatry ,Substantia Nigra ,Psychiatry and Mental health ,Neurology ,nervous system ,biology.protein ,Autoreceptor ,NMDA receptor ,Neurology (clinical) ,Dizocilpine Maleate ,Excitatory Amino Acid Antagonists ,030217 neurology & neurosurgery ,medicine.drug ,Signal Transduction - Abstract
Phencyclidine (PCP) administration is commonly used to model schizophrenia in laboratory animals. While PCP is well-characterized as an antagonist of glutamate-sensitive N-methyl-D-aspartate (NMDA) receptors, its effects on dopamine signaling are not well understood. Here we used whole-cell and cell-attached patch-clamp electrophysiology of substantia nigra dopamine neurons to determine the effects of acute and subchronic PCP exposure on both dopamine D2 autoreceptor-mediated currents and burst firing evoked by glutamate receptor activation. Acute PCP affected D2 autoreceptor-mediated currents through two apparently distinct mechanisms: a low-concentration dopamine transporter (DAT) inhibition and a high-concentration potassium (GIRK) channel inhibition. Subchronic administration of PCP (5 mg/kg, i.p., every 12 h for 7 days) decreased sensitivity to low dopamine concentrations, and also enhanced evoked burst firing of dopamine neurons. These findings suggest the effects of PCP on dopaminergic signaling in the midbrain could enhance burst firing and contribute to the development of schizophreniform behavior.
- Published
- 2019