ACOUSTIC STARTLE, PREPULSE INHIBITION, LOCOMOTION, AND LATENT INHIBITION IN THE NEUROLEPTIC-RESPONSIVE (NR) AND NEUROLEPTIC-NONRESPONSIVE (NNR) LINES OF MICE

The acoustic startle reflex (ASR) is inhibited by low intensity acoust ic stimuli (prepulse inhibition; PPI) delivered prior to the startle s timulus. PPT may reflect underlying sensorimotor processes involved in the filtering of exteroceptive stimuli for their cognitive or physiol ogical relevance. Latent inhibition (LI) is a cognitive process in whi ch pre-exposure to the conditioned stimulus (CS) produces pro-active i nterference with the acquisition of an associative learning task. LI i s thought to reflect a selective attention mechanism that contributes to an organism's ability to adjust its behavior to changing contingenc ies of reinforcement. In the present series of experiments, the ASR, P PI at three prepulse intensities (56, 68, and 80 dB), locomotor activi ty, and LI using an active avoidance paradigm were assessed in mice bi directionally selected from a heterogeneous stock for response (NR lin e) or nonresponse (NNR line) to neuroleptic-induced catalepsy. A rando mly selected line was used as the control. Mice from the NNR line disp layed weak startle responses and a complete absence of PPI. In contras t, the NR line displayed the largest ASR and the greatest PPI. The con trol line displayed ASRs and PPI values inter mediate to the selected lines. Locomotor activity which is known to affect LI was lowest in th e NR line but was similar in the NNR and control lines. In the LI para digm, acquisition of the avoidance response was impaired in mice from the NR and control lines that were pre-exposed to the auditory CS (nor mal response). In contrast, the acquisition of the avoidance response in the NNR line was similar in CS pre-exposed and CS non-pre-exposed a nimals. Overall, the results demonstrate that some of the same genetic factors which regulate neuroleptic response also play a significant r ole in PPI and LI.