Evaluating the antipsychotic profile of the preferential PDE10A inhibitor, papaverine

The aim of the study was to evaluate the antipsychotic profile of PAP in rats using PPI. PPI deficits were induced in rats by apomorphine (APO; 0.1, 0.5 mg/kg) or d-amphetamine (AMPH; 4 mg/kg). PAP (3, 10, 30 mg/kg) or haloperidol (HAL; 0.1 mg/kg) was tested against these agonists in Sprague-Dawley (SD) or Wistar (WI) rats. Prepulse intervals ranged from 10 to 120 ms. Further tests evaluated the effects of PAP on spontaneous locomotion, AMPH (1 mg/kg)-induced hyperlocomotion, and core body temperature. HAL reversed APO-induced PPI deficits but PAP failed to reverse APO- and AMPH-induced PPI deficits at all doses, strains, pretreatment times, and prepulse intervals. PAP (30 mg/kg) significantly reduced AMPH hyperlocomotion in SD rats, and a similar pattern was detected in WI rats. This PAP dose also strongly reduced spontaneous locomotion and temperature in SD rats. Our study does not support an antipsychotic-like profile of PAP in dopaminergic PPI models.