title: Aberrant dopamine D2-like receptor function in a rodent model of schizophrenia.
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.
authors.affiliation: Department of Pharmacology, Center for Biomedical Neuroscience, University of Texas Health Science Center, 7703 Floyd Curl Drive, MC 7764, San Antonio, TX 78229, USA.
authors.forename: Stephanie M
authors.initials: SM
authors.lastname: Perez
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Lodge
mesh_terms: D000477:Alkylating Agents; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D004298:Dopamine / Q000502:physiology; D018491:Dopamine Agonists / Q000494:pharmacology; D065127:Dopamine D2 Receptor Antagonists; D059290:Dopaminergic Neurons / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D005260:Female; D008746:Methylazoxymethanol Acetate / Q000031:analogs & derivatives; D009043:Motor Activity / Q000187:drug effects; D009714:Nucleus Accumbens / Q000378:metabolism; D019257:Quinpirole / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D017448:Receptors, Dopamine D2 / Q000819:agonists / Q000502:physiology*; D050638:Receptors, Dopamine D4 / Q000819:agonists / Q000037:antagonists & inhibitors; D012559:Schizophrenia / Q000139:chemically induced / Q000378:metabolism*; D017557:Ventral Tegmental Area / Q000378:metabolism
chemical_list: D000477:Alkylating Agents; D018491:Dopamine Agonists; D065127:Dopamine D2 Receptor Antagonists; D017448:Receptors, Dopamine D2; D050638:Receptors, Dopamine D4; D019257:Quinpirole; D008746:Methylazoxymethanol Acetate; C030667:methylazoxymethanol; D004298:Dopamine