PT  - JOURNAL ARTICLE
AU  - Susan E Martelle
AU  - Susan H Nader
AU  - Paul W Czoty
AU  - William S John
AU  - Angela N Duke
AU  - Pradeep K Garg
AU  - Sudha Garg
AU  - Amy H Newman
AU  - Michael A Nader
TI  - Further Characterization of Quinpirole-Elicited Yawning As a Model of Dopamine D3 Receptor Activation in Male and Female Monkeys
AID  - 10.1124/jpet.114.214833
DP  - 2014 Jan 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - jpet.114.214833
4099  - http://jpet.aspetjournals.org/content/early/2014/05/29/jpet.114.214833.short
4100  - http://jpet.aspetjournals.org/content/early/2014/05/29/jpet.114.214833.full
AB  - The dopamine (DA) D3 receptor (DRD3) has been associated with impulsivity, pathological gambling and drug addiction making it a potential target for pharmacotherapy development. Positron emission tomography (PET) studies using the DRD3-preferring radioligand [11C]-(+)-propyl-hexahydro-naphtho-oxazin ([11C]PHNO) have shown higher binding potentials in drug abusers compared to control subjects. Preclinical studies have examined DRD3 receptor activation using the DA agonist quinpirole and the unconditioned behavior of yawning. However, the relationship between quinpirole-elicited yawning and DRD3 receptor availability has not been determined. In Experiment 1, 10 drug-naive male rhesus monkeys were scanned with [11C]PHNO and the ability of quinpirole (0.01-0.3 mg/kg, i.m.) to elicit yawning was examined. Significant relationships between DRD3 receptor availability and quinpirole-induced yawns were noted in several brain regions. Experiment 2 replicated earlier findings that a history of cocaine self-administration did not affect quinpirole-induced yawning and extended this to examine monkeys 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 to controls. Finally, quinpirole-elicited yawning was studied in drug-naive female monkeys and compared to drug-naive male. Sex differences were noted, with quinpirole being more potent and significantly eliciting more yawns in males compared to females. Taken together these findings support the use of quinpirole-elicited yawning as a behavioral tool for examining DRD3 activation in monkeys and that both drug history and sex may influence individual sensitivity to the behavioral effects of DRD3 compounds.