Evaluation of the Selective A2A Receptor Antagonist, SCH 412348, and the D2/D3 Receptor Agonist Pramipexole in Rat Models of Psychotic and Obsessive Behavior

TL;DRAbstract

Dopamine D2/D3 receptor agonists, used to treat Parkinson's Disease (PD), have serious side effects, including hallucinations and obsessive behavior. Adenosine A2A receptor antagonists have been proposed as a PD treatment, but little has been done to evaluate potential psychiatric side‐effects. We tested the D2/D3 receptor agonist pramipexole, and the selective A2A receptor antagonist SCH 412348 in rodent prepulse inhibition (PPI). Pramipexole (0.3–3 mg/kg) induced a significant PPI deficit in rats and mice. PPI is used to preclinically model psychotic‐like behavior. Ropinirole (1–30 mg/kg) and SCH 412348 (0.3–3 mg/kg) had no effect. Currently there is no preclinical model of the obsessive behavior side effect associated with D2/D3 receptor agonists. To address this, we trained water‐deprived rats that licking a water spout would result in a mild footshock. We hypothesized that pramipexole‐treated animals would favor the rewarding stimulus over the punishing stimulus manifested as incr

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