Routine post-weaning handling of rats prevents isolation rearing-induced deficit in prepulse inhibition

Abstract

Rats reared under isolation conditions from weaning present a number of behavioral changes compared to animals reared under social conditions (group housing). These changes include deficits in prepulse inhibition (PPI) of the startle reflex to a loud sound. PPI refers to the reduction of the magnitude of the startle reflex when a relatively weak stimulus (the prepulse) precedes by an appropriate time interval the intense startle-elicing stimulus (the pulse). PPI is useful for studying sensorimotor integration. The present study evaluated the effect of handling on the impairment of PPI induced by isolation-rearing. Male Wistar rats (N = 11-15/group) were housed in groups (5 per cage and handled three times a week) or isolated (housed individually) since weaning (21 days) for 10 weeks when they reach approximately 150 g. The isolated rats were divided into "minimally handled" animals (handled once a week for cleaning purposes only) or "handled" animals (handled three times a week). This handling consisted of grasping the rat by the tail and moving it to a clean cage (approximately 5 s). A statistically significant reduction (52%) in the PPI test was found only in the isolated group with minimal handling while no difference was seen between grouped animals and isolated handled animals. These results indicate that isolation rearing causes disruption in the PPI at adult age, which serves as an index of attention deficit. This change in the sensory processing of information induced by postweaning isolation can be prevented by handling during the development of the animal.

Behavioural and neurochemical effects of post-weaning social isolation in rodents—Relevance to developmental neuropsychiatric disorders

“…Isolation-reared mice (Sakaue et al, 2003;Varty et al, 2006) and rats show a robust reduction in PPI of acoustic startle (Geyer et al, 1993). This finding has been replicated in a large variety of laboratories in both male and female Lister hooded (Cilia et al, 2005bDayWilson et al, 2006;Varty et al, 1999b), Long-Evans (Binder et al, 2001;Powell et al, 2003Powell et al, , 2002 and Sprague-Dawley rats (Geyer et al, 1993;Varty et al, 1999a), with less consistent and smaller effects seen in Wistar (Domeney and Feldon, 1998;Rosa et al, 2005;Weiss et al, 2000Weiss et al, , 1999Weiss and Feldon, 2001) and Lewis strains but it may not occur in isolated Fischer (Varty and Geyer, 1998) rats ( Table 2). As previously discussed in Section 2 above the development of PPI may also be dependent on the housing environment and is not seen in Wistar rats raised on a grid rather than a sawdust floor (Weiss et al, 1999).…”

“…However, the PPI deficit is developmentally specific and does not occur when adult rats are isolated for an 8-week period (Wilkinson et al, 1994). Other groups have also found that the PPI deficit can be lost by assessment of locomotor activity less than 1 week prior to PPI (Domeney and Feldon, 1998) or handling during the isolation period (KrebsThomson et al, 2001) even briefly (grasping the tail three times a week) will prevent the development of PPI deficits (Rosa et al, 2005). So an adequate recovery period of at least 7 days should be left between test procedures or repeated PPI testing if this is to be performed (Domeney and Feldon, 1998;Varty and Higgins, 1995).…”

“…In contrast, the basal level of activity may be elevated from group housed controls from the outset of placing isolated Wistar rats in a novel arena (Domeney and Feldon, 1998;Heidbreder et al, 2000). This also demonstrates the need to record the response to novelty over a sufficient time period to enable the temporal profile to be recorded and could explain the few reports where the response to a novel arena has appeared unaltered (Rosa et al, 2005) or even reduced during the first 5 min due to initial freezing (Holson et al, 1991). Furthermore, even brief periods of handling twice a week are sufficient to prevent this inappropriate habituation to a novel environment (Holson et al, 1991).…”

Social Isolation Rearing Induces Neuropsychiatric Diseases: Updated Overview

“…Since schizophrenia manifests as a constellation of symptoms such as polydipsia, reversal learning, impaired prepulse inhibition, and many others, animal studies have focused on these symptoms. Investigating the occurrence of this disorder, polydipsia in male Sprague-Dawley rats after 62 days of social isolation [9], reversal learning in male Sprague-Dawley rats after 52 days of social isolation [10], and prepulse inhibition in male Wistar rats after 21 days of social isolation [11] were assessed. It was seen that schizophrenia-related symptoms occurred in social isolation reared rats.…”

Development and characterization of chronic animal models of schizophrenia

“…Plenty of evidence suggest that long-term postweaning social isolation may also induce impaired PPI in rodents, but resocialization may lead to recovery; however, the data are somewhat inconsistent [4,45,[134][135][136][137][138][139][140][140][141][142][143]. It is assumed that changes in the prefrontal cortex after social isolation and/or imbalances between neural connections within the cortico-striato-limbic circuitry lead to the observed PPI disturbances [4].…”