RESUMEN
The acoustic startle reflex (ASR) is inhibited by low intensity acoustic stimuli (prepulse inhibition; PPI) delivered prior to the startle stimulus. PPI may reflect underlying sensorimotor processes involved in the filtering of exteroceptive stimuli for their cognitive or physiological relevance. Latent inhibition (LI) is a cognitive process in which pre-exposure to the conditioned stimulus (CS) produces pro-active interference with the acquisition of an associative learning task. LI is thought to reflect a selective attention mechanism that contributes to an organism's ability to adjust its behavior to changing contingencies of reinforcement. In the present series of experiments, the ASR, PPI at three prepulse intensities (56, 68, and 80 dB), locomotor activity, and LI using an active avoidance paradigm were assessed in mice bidirectionally selected from a heterogeneous stock for response (NR line) or nonresponse (NNR line) to neuroleptic-induced catalepsy. A randomly selected line was used as the control. Mice from the NNR line displayed weak startle responses and a complete absence of PPI. In contrast, the NR line displayed the largest ASR and the greatest PPI. The control line displayed ASRs and PPI values intermediate to the selected lines. Locomotor activity which is known to affect LI was lowest in the NR line but was similar in the NNR and control lines. In the LI paradigm, acquisition of the avoidance response was impaired in mice from the NR and control lines that were pre-exposed to the auditory CS (normal response). In contrast, the acquisition of the avoidance response in the NNR line was similar in CS pre-exposed and CS non-pre-exposed animals. Overall, the results demonstrate that some of the same genetic factors which regulate neuroleptic response also play a significant role in PPI and LI.
Asunto(s)
Actividad Motora , Reflejo de Sobresalto , Estimulación Acústica , Análisis de Varianza , Animales , Reacción de Prevención , Catalepsia/fisiopatología , Catalepsia/psicología , Masculino , Ratones , Ratones Endogámicos , Psicología del EsquizofrénicoRESUMEN
The acoustic startle response (ASR), prepulse inhibition (PPI) of the ASR and the effects of haloperidol on the ASR and PPI were examined in C57BL/6J (B6) and DBA/2 (D2) inbred mouse strains and their F1 and F2 progeny. The startle stimulus was a 60-ms, 110-dB, 10-kHz tone; the prepulse stimuli were 20-ms, white noise bursts at 56, 68 and 80 dB against a 50-dB background presented 100-ms before the startle pulse. The B6 strain showed modest PPI (25-40%); in contrast, the D2 strain showed on average no PPI and numerous individuals showed prepulse augmentation (PPA). The F2 progeny showed an intermediate PPI; however, the extreme values ranged from 200% PPA to essentially 100% PPI. Haloperidol in dose-dependent fashion, increased PPI in both the B6 and D2 strains; the threshold dose was in the range of 0.1-0.2 mg/kg. Raclopride (0.3 mg/kg), clozapine (2 mg/kg) and risperidone (0.4 mg/kg) also increased PPI in both strains. The effects of haloperidol (0.4 mg/kg) on PPI in 140 F2 progeny were examined. For all prepulse intensities, there were highly significant (r > 0.80) and negative correlations between baseline PPI and the haloperidol-induced change in PPI. Thus, those animals that showed the greatest PPA showed the greatest haloperidol-induced increase in PPI. There was, however, significant variance in the haloperidol response; plots of the regression residuals showed the most and least responsive animals differed by almost 100% in effect on PPI. The F2 progeny were subsequently phenotyped for haloperidol-induced catalepsy. There was no association between the variation in effects on catalepsy and PPI. However, it was observed that those individuals with the poorest baseline PPI were catalepsy non-responsive.