Effects of pergolide on sensorimotor gating of the startle reflex in rats

Rationale: Prepulse inhibition (PPI), a cross-species measure of sensorimot or gating, is impaired in certain neuropsychiatric disorders, including sch izophrenia. This study was designed to assess the effects of the D2-family agonist pergolide in rats, in anticipation of human studies of the dopamine rgic regulation of PPI. Methods: The effects of pergolide (0.0001-0.5 mg/kg ) on PPI of the acoustic startle reflex were studied in rats using a wide r ange of prepulse intensities [1-15 dB(A) over background] and prepulse inte rvals (5-100 ms, onset to onset). Studies also examined the effects of the D2 antagonist haloperidol on pergolide-induced changes in PPI. Results: Per golide exhibited dose- and stimulus-dependent effects on PPI. Pergolide inc reased PPI when startle stimuli were preceded by weak prepulses [1-5 dB(A) over background] at the longest prepulse interval (100 ms), or intense prep ulses [15 dB(A) over background] at short prepulse intervals (5-20 ms). Per golide (0.5 mg/kg) also decreased PPI elicited by intense prepulses at long intervals (60-100 ms). Both PPI-enhancing and PPI-disruptive effects of pe rgolide were reversed by the D2 antagonist haloperidol. Conclusions: These effects of pergolide suggest that D2 substrates mediate opposing, influence s on PPI under different stimulus conditions. The dopaminergic regulation o f sensorimotor gating appears to interact with stimulus characteristics suc h as relative intensity and temporal separation, allowing for dynamic shift s in both the quantity and quality of "gated" information.