Aberrant dopamine D2-like receptor function in a rodent model of schizophrenia

Stephanie M. Perez, Daniel J Lodge

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Based on the observation that antipsychotic medications display antagonist properties at dopamine D2-like receptors, aberrant dopamine signaling has been proposed to underlie psychosis in patients with schizophrenia. Thus, it is not surprising that considerable research has been devoted to understanding the mechanisms involved in the antipsychotic action of these compounds. It is important to note that the majority of these studies have been performed in "normal" experimental animals. Given that these animals do not possess the aberrant neuronal information processing typically associated with schizophrenia, the aim of the current study was to examine the dopamine D2 receptor system in a rodent model of schizophrenia. Here, we demonstrate that methylazoxymethanol acetate (MAM)-treated rats display an enhanced effect of quinpirole on dopamine neuron activity and an aberrant locomotor response to D2-like receptor activation, suggesting changes in postsynaptic D2-like receptor function. To better understand the mechanisms underlying the enhanced response to D2-like ligands in MAM-treated rats, we examined the expression of D2, D3, and dopamine transporter mRNA in the nucleus accumbens and ventral tegmental area by quantitative reverse transcription-polymerase chain reaction. MAM-treated rats displayed a significant increase in dopamine D3 receptor mRNA expression in the nucleus accumbens with no significant changes in the expression of the D2 receptor. Taken together, these data demonstrate robust alterations in dopamine D2-like receptor function in a rodent model of schizophrenia and provide evidence that preclinical studies examining the mechanisms of antipsychotic drug action should be performed in animal models that mirror aspects of the abnormal neuronal transmission thought to underlie symptoms of schizophrenia.

Original languageEnglish (US)
Pages (from-to)288-295
Number of pages8
JournalJournal of Pharmacology and Experimental Therapeutics
Volume343
Issue number2
DOIs
StatePublished - Nov 2012

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Dopamine D2 Receptors
Methylazoxymethanol Acetate
Rodentia
Schizophrenia
Antipsychotic Agents
Nucleus Accumbens
Dopamine D3 Receptors
Quinpirole
Messenger RNA
Dopamine Plasma Membrane Transport Proteins
Ventral Tegmental Area
Dopaminergic Neurons
Locomotion
Automatic Data Processing
Psychotic Disorders
Reverse Transcription
Dopamine
Animal Models
Ligands
Polymerase Chain Reaction

ASJC Scopus subject areas

  • Pharmacology
  • Molecular Medicine

Cite this

Aberrant dopamine D2-like receptor function in a rodent model of schizophrenia. / Perez, Stephanie M.; Lodge, Daniel J.

In: Journal of Pharmacology and Experimental Therapeutics, Vol. 343, No. 2, 11.2012, p. 288-295.

Research output: Contribution to journalArticle

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