Dose and time response analysis of apomorphine's effect on prepulse inhibition of acoustic startle.

Previous studies have suggested a dopaminergic modulation of the acoustic startle response. Using a 73 dB tone as a prestimulus to 100 dB white noise (PP trials), and 100 dB white noise alone (WN trials) during a 5-30 min or 5-90 min session, we found that IP injections of apomorphine (APO; 1.6 and 3.2 mg/kg) initially elevated PP trial means to levels statistically indistinguishable from WN trial means. These results suggest that APO can dose-dependently disrupt prepulse inhibition of the acoustic startle response. After the initial startle amplitude elevation 5-10 min post-injection in the 5-90 min protocol, startle response amplitude of the 3.2 mg/kg APO dose group decreased during successive testing periods, in contrast to the pattern of vehicle controls, which did not decrease during the session. The results of this extended time course study suggest complex time and dose effects of APO on reflex modification mechanisms. The finding that systemic APO administration produces a loss of prepulse inhibition in rodents underscores the pivotal role of DA neurotransmission in the mediation of startle behavior.