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Eur Neuropsychopharmacol. 2019 Mar;29(3):444-449. doi: 10.1016/j.euroneuro.2019.01.108. Epub 2019 Jan 25.

Acute and subchronic PCP attenuate D2 autoreceptor signaling in substantia nigra dopamine neurons.

Author information

1
Hasselt University, Department of Physiology, Hasselt 3500, Belgium.
2
Oklahoma Medical Research Foundation, Aging & Metabolism Research Program, Oklahoma City, OK 73104, USA; University of Texas Health, San Antonio, Department of Cellular & Integrative Physiology, San Antonio, TX 78228, USA.
3
Oklahoma Medical Research Foundation, Aging & Metabolism Research Program, Oklahoma City, OK 73104, USA; University of Texas Health, San Antonio, Department of Cellular & Integrative Physiology, San Antonio, TX 78228, USA. Electronic address: mike-beckstead@omrf.org.

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.

KEYWORDS:

Burst; DAT; Dopamine; GIRK; Mouse; Phencyclidine

PMID:
30686631
PMCID:
PMC6421099
[Available on 2020-03-01]
DOI:
10.1016/j.euroneuro.2019.01.108
[Indexed for MEDLINE]

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