Esumi, Satoru Department of Pharmacy, Okayama University Hospital
Sagara, Hidenori Department of Pharmaceutical Information Sciences, Matsuyama University
Nakamoto, Akihiko Department of Pharmacy, Okayama University Hospital
Kawasaki, Yoichi Department of Pharmacy, Okayama University Hospital
Gomita, Yutaka School of Pharmacy, Shujitsu University
Sendo, Toshiaki Department of Pharmacy, Okayama University Hospital
Rationale: It was recently demonstrated that the priming stimulation effect (PSE) in the runway model of intracranial self-stimulation (ICSS) can be used as a model system to study the motivational effects of drugs. However, the characteristics of this navel experimental model have not been fully clarified. Objective: To elucidate the involvement of dopamine uptake inhibition in motivated behavior and the difference in experimental characteristics between closely related experimental models, we investigated the effects of the dopamine uptake inhibitor GBR12909 in the runway ICSS model, in the forced swimming test (FST), and on conditioned place preference (CPP). In addition, the role of dopamine receptor signaling in the runway model was evaluated using dopamine receptor agonists and antagonists. Results: GBR12909 dose-dependently increased running speed on the runway and decreased immobility time in the FST without affecting the time spent in the drug-associated compartment in CPP tests. The effect of GBR12909 in the runway model was inhibited by pre-treatment with the dopamine receptor antagonists haloperidol and raclopride. The dopamine receptor agonists SKF38393 and quinpirole dose-dependently decreased running speed. Conclusions: These results demonstrate that GBR12909 displays motivation-enhancing and antidepressant-like effects without place conditioning effects. In addition, the mechanisms of PSE enhancement in the runway ICSS model are different from those underlying closely associated experimental models and are mediated by increases in dopamine signaling.
Forced swimming test
Conditioned place preference
Behavioural Brain Research
(C) 2012 Elsevier B.V. All rights reserved.
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