title: Further characterization of quinpirole-elicited yawning as a model of dopamine D3 receptor activation in male and female monkeys.
abstract: The dopamine (DA) D3 receptor (D3R) has been associated with impulsivity, pathologic gambling, and drug addiction, making it a potential target for pharmacotherapy development. Positron emission tomography studies using the D3R-preferring radioligand [(11)C]PHNO ([(11)C](+)-propyl-hexahydro-naphtho-oxazin) have shown higher binding potentials in drug abusers compared with control subjects. Preclinical studies have examined D3R receptor activation using the DA agonist quinpirole and the unconditioned behavior of yawning. However, the relationship between quinpirole-elicited yawning and D3R receptor availability has not been determined. In Experiment 1, eight drug-naive male rhesus monkeys were scanned with [(11)C]PHNO, and the ability of quinpirole (0.01-0.3 mg/kg i.m.) to elicit yawning was examined. Significant positive (globus pallidus) and negative (caudate nucleus, putamen, ventral pallidum, and hippocampus) relationships between D3R receptor availability and quinpirole-induced yawns were noted. Experiment 2 replicated earlier findings that a history of cocaine self-administration (n = 11) did not affect quinpirole-induced yawning and extended this to examine monkeys (n = 3) with a history of methamphetamine (MA) self-administration and found that monkeys with experience self-administering MA showed greater potency and significantly higher quinpirole-elicited yawning compared with controls. Finally, quinpirole-elicited yawning was studied in drug-naive female monkeys (n = 6) and compared with drug-naive male monkeys (n = 8). Sex differences were noted, with quinpirole being more potent and eliciting significantly more yawns in males compared with females. Taken together these findings support the use of quinpirole-elicited yawning as a behavioral tool for examining D3R activation in monkeys and that both drug history and sex may influence individual sensitivity to the behavioral effects of D3R compounds.
authors.affiliation: Departments of Physiology and Pharmacology (S.E.M., S.H.N., P.W.C., W.S.J., A.N.D., M.A.N.) and Radiology (P.K.G., S.G., M.A.N.), Wake Forest School of Medicine, Winston-Salem, North Carolina; and the Intramural Research Program (A.H.N.), National Institute on Drug Abuse, Baltimore, Maryland.
authors.forename: Susan E
authors.initials: SE
authors.lastname: Martelle
authors.affiliation: Departments of Physiology and Pharmacology (S.E.M., S.H.N., P.W.C., W.S.J., A.N.D., M.A.N.) and Radiology (P.K.G., S.G., M.A.N.), Wake Forest School of Medicine, Winston-Salem, North Carolina; and the Intramural Research Program (A.H.N.), National Institute on Drug Abuse, Baltimore, Maryland.
authors.forename: Susan H
authors.initials: SH
authors.lastname: Nader
authors.affiliation: Departments of Physiology and Pharmacology (S.E.M., S.H.N., P.W.C., W.S.J., A.N.D., M.A.N.) and Radiology (P.K.G., S.G., M.A.N.), Wake Forest School of Medicine, Winston-Salem, North Carolina; and the Intramural Research Program (A.H.N.), National Institute on Drug Abuse, Baltimore, Maryland.
authors.forename: Paul W
authors.initials: PW
authors.lastname: Czoty
authors.affiliation: Departments of Physiology and Pharmacology (S.E.M., S.H.N., P.W.C., W.S.J., A.N.D., M.A.N.) and Radiology (P.K.G., S.G., M.A.N.), Wake Forest School of Medicine, Winston-Salem, North Carolina; and the Intramural Research Program (A.H.N.), National Institute on Drug Abuse, Baltimore, Maryland.
authors.forename: William S
authors.initials: WS
authors.lastname: John
authors.affiliation: Departments of Physiology and Pharmacology (S.E.M., S.H.N., P.W.C., W.S.J., A.N.D., M.A.N.) and Radiology (P.K.G., S.G., M.A.N.), Wake Forest School of Medicine, Winston-Salem, North Carolina; and the Intramural Research Program (A.H.N.), National Institute on Drug Abuse, Baltimore, Maryland.
authors.forename: Angela N
authors.initials: AN
authors.lastname: Duke
authors.affiliation: Departments of Physiology and Pharmacology (S.E.M., S.H.N., P.W.C., W.S.J., A.N.D., M.A.N.) and Radiology (P.K.G., S.G., M.A.N.), Wake Forest School of Medicine, Winston-Salem, North Carolina; and the Intramural Research Program (A.H.N.), National Institute on Drug Abuse, Baltimore, Maryland.
authors.forename: Pradeep K
authors.initials: PK
authors.lastname: Garg
authors.affiliation: Departments of Physiology and Pharmacology (S.E.M., S.H.N., P.W.C., W.S.J., A.N.D., M.A.N.) and Radiology (P.K.G., S.G., M.A.N.), Wake Forest School of Medicine, Winston-Salem, North Carolina; and the Intramural Research Program (A.H.N.), National Institute on Drug Abuse, Baltimore, Maryland.
authors.forename: Sudha
authors.initials: S
authors.lastname: Garg
authors.affiliation: Departments of Physiology and Pharmacology (S.E.M., S.H.N., P.W.C., W.S.J., A.N.D., M.A.N.) and Radiology (P.K.G., S.G., M.A.N.), Wake Forest School of Medicine, Winston-Salem, North Carolina; and the Intramural Research Program (A.H.N.), National Institute on Drug Abuse, Baltimore, Maryland.
authors.forename: Amy H
authors.initials: AH
authors.lastname: Newman
authors.affiliation: Departments of Physiology and Pharmacology (S.E.M., S.H.N., P.W.C., W.S.J., A.N.D., M.A.N.) and Radiology (P.K.G., S.G., M.A.N.), Wake Forest School of Medicine, Winston-Salem, North Carolina; and the Intramural Research Program (A.H.N.), National Institute on Drug Abuse, Baltimore, Maryland mnader@wakehealth.edu.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Nader
mesh_terms: D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D018491:Dopamine Agonists / Q000494:pharmacology*; D005260:Female; D008253:Macaca mulatta; D008297:Male; D008694:Methamphetamine / Q000494:pharmacology; D023421:Models, Animal; D019257:Quinpirole / Q000494:pharmacology*; D017448:Receptors, Dopamine D2 / Q000502:physiology; D050637:Receptors, Dopamine D3 / Q000502:physiology*; D012646:Self Administration; D012727:Sex Characteristics; D015000:Yawning / Q000187:drug effects*
chemical_list: D018491:Dopamine Agonists; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D019257:Quinpirole; D008694:Methamphetamine