title: Perinatal Treatments with the Dopamine D₂-Receptor Agonist Quinpirole Produces Permanent D₂-Receptor Supersensitization: a Model of Schizophrenia.
abstract: Repeated daily treatments of perinatal rats with the dopamine D2-receptor (D2-R) agonist quinpirole for a week or more produces the phenomenon of 'priming'-gradual but long-term sensitization of D2-R. In fact a daily dose of quinpirole as low as 50 µg/kg/day is adequate for sensitizing D2-R. Primed rats as neonates and in adolescence, when acutely treated with quinpirole display enhanced eating/gnawing/nursing on dams, also horizontal locomotor activity. Between 3 and 5 weeks of age, acute quinpirole treatment of primed rats produces profound vertical jumping with paw treading-a behavior that is not observed in control rats. At later ages acute quinpirole treatment is associated with enhanced yawning, a D2-R-associated behavior. This long-term D2-R supersensitivity is believed to be life-long, despite the relatively brief period of D2-R priming near the time of birth. D2-R supersensitivity is not associated with an increase in the number or affinity of D2-R, as assessed in the striatum of rats; nor is it induced with the D3-R agonist 7-OH-DPAT. However, quinpirole-induced D2-R supersensitivity is associated with cognitive deficits, also a deficit in pre-pulse inhibition and in neurotrophic factors, and low levels of the transcript regulator of G-protein signaling (RGS) RGS9 in brain; and acute reversal of these alterations by the antipsychotic agent olanzapine. In sum, rats ontogenetically D2-R supersensitized have face validity, construct validity and predictive ability for schizophrenia.
authors.affiliation: Department of Biomedical Sciences, Quillen College of Medicine, East Tennessee State University, Johnson City, TN, 37614, USA. kostrzew@etsu.edu.
authors.forename: Richard M
authors.initials: RM
authors.lastname: Kostrzewa
authors.affiliation: Department of Toxicology and Occupational Health Protection, Public Health Faculty, Medical University of Silesia, 40-752, Katowice Ligota, Poland.
authors.forename: Przemysław
authors.initials: P
authors.lastname: Nowak
authors.affiliation: Department of Nurse, High School of Strategic Planning, 41-303, Dabrowa Gornicza, Poland.
authors.forename: Ryszard
authors.initials: R
authors.lastname: Brus
authors.affiliation: Department of Biomedical Sciences, Quillen College of Medicine, East Tennessee State University, Johnson City, TN, 37614, USA.
authors.forename: Russell W
authors.initials: RW
authors.lastname: Brown
mesh_terms: D000662:Amphetamines / Q000494:pharmacology; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D018491:Dopamine Agonists / Q000494:pharmacology*; D005089:Exocytosis / Q000187:drug effects; D005260:Female; D019204:GTP-Binding Proteins / Q000378:metabolism; D006801:Humans; D008124:Locomotion; D008297:Male; D019257:Quinpirole / Q000494:pharmacology*; D051381:Rats; D017448:Receptors, Dopamine D2 / Q000187:drug effects* / Q000378:metabolism; D012559:Schizophrenia / Q000378:metabolism* / Q000503:physiopathology; D012737:Sex Factors
chemical_list: D000662:Amphetamines; D018491:Dopamine Agonists; D017448:Receptors, Dopamine D2; D019257:Quinpirole; D019204:GTP-Binding Proteins
keywords: D2 receptor; Dopamine; Priming; Quinpirole; Receptor supersensitivity