Effects of single and repeated exposure to apomorphine on the acoustic startle reflex and its inhibition by a visual prepulse.

The acoustic startle reflex (ASR) is inhibited by startle-irrelevant stimuli that briefly precede reflex elicitation. This effect, prepulse inhibition (PPI), is reduced in strength for animals that have received dopamine agonists, such as apomorphine (APO). Reduction in PPI is most evident for weak masked noise prepulses, thus suggesting that APO disrupts the reception of stimuli to the extent that they present a low signal-to-noise ratio. Here we examine the effect of APO on PPI produced by non-masked visual prepulses. Light flashes were given at two intensities, 40, 70, 110, or 220 ms before ASR elicitation. In phase 1 (5 weeks in duration) half of the animals received one weekly injection of APO (0.5 mg/kg, IP) and one of vehicle (VEH), while the other half received two injections of VEH. Within these groups, half were tested 30 min after the injections, the other half kept test naive (four groups total). In phase 2, following a 4-week rest, all groups were tested after a low dose of APO (0.1 mg/kg) and VEH, 1 week apart. APO eliminated PPI for a dim flash and reduced PPI for a brighter flash to a level normally obtained with the dim flash, while increasing both ASR control values and activity. The bright light was maximally effective at a lead time of 70 ms and APO did not alter this value. Because in general the time of maximal inhibition varies with prepulse intensity for visual stimuli, the finding that the time of the peak remained constant reveals that APO has its effect on inhibition rather than on effective stimulus intensity. In phase 2, APO reduced PPI with no sign of sensitization from past drug exposure. However, APO increased the ASR only in groups previously exposed to APO, indicating behavioral sensitization. The differential effects of repeated exposure on these response measures suggest that neural substrates for the several behavioral effects of APO function at least in part independently.