Opposite effects of short- and long-duration isolation on ultrasonic vocalization, startle and prepulse inhibition in rats

Housing conditions change the sensorimotor gating and the emotional state of rats. The prepulse inhibition (PPI) is a reduction in the startle reflex to loud sounds when they are preceded by acoustic stimuli of low-intensity, and this test has been considered to be a useful measurement of the functioning of sensory gating in animals and man. Rats reared under conditions of isolation from the time of weaning, but not for 1 week at adult age, display clear deficits in prepulse inhibition and in sensorimotor gating. Ultrasound vocalizations (USVs) at 20-24 kHz are the usual defensive responses of rats exposed to threatening conditions such as novel situations. The amount of emissions of ultrasound vocalizations at these frequencies depends on whether the aversive stimuli are presented either alone or in combination. Given this background we evaluated the prepulse inhibition and the emission of ultrasound vocalizations in response to novelty in rats isolated for 1 day or 2 weeks and compared the results to those in grouped rats. We also examined whether the anxiolytic agent midazolam (0.5 and 1.0 mg/kg) could reverse the effects of isolation under the experimental conditions used. Rats isolated for 1 day showed a significant increase in the number and duration of USVs together with an enhancement in the startle response to loud sounds, which were antagonized in a dose-dependent manner by midazolam. On the other hand, 2-week isolation had the effect of reducing the number of USVs emitted at 20-24 kHz without changing the startle response. The PPI was not changed by isolation, irrespective of the duration of isolation (1 day or 2 weeks). The results suggest that 1 day and 2 weeks of isolation have opposite effects on the emotional state of the animals. While short periods of isolation cause an anxiolytic-sensitive enhancement of the defensive responses, longer periods tend to reduce the defensive reaction of the animals to aversive stimuli. Based on these results, this work presents a novel method for induction of two different modes of defensive response, which are proposed to be mediated by separate neural substrates in rats. Also, isolation from 1 day to 2 weeks has no effect on the expression of prepulse inhibition and, by extension, on the functioning of the sensory gating.