Pro-social 50-kHz ultrasonic communication in rats: post-weaning but not post-adolescent social isolation leads to social impairments—phenotypic rescue by re-socialization

Abstract

Rats are highly social animals and social play during adolescence has an important role for social development, hence post-weaning social isolation is widely used to study the adverse effects of juvenile social deprivation and to induce behavioral phenotypes relevant to neuropsychiatric disorders, like schizophrenia. Communication is an important component of the rat's social behavior repertoire, with ultrasonic vocalizations (USV) serving as situation-dependent affective signals. High-frequency 50-kHz USV occur in appetitive situations and induce approach behavior, supporting the notion that they serve as social contact calls; however, post-weaning isolation effects on the behavioral changes displayed by the receiver in response to USV have yet to be studied. We therefore investigated the impact of post-weaning isolation on socio-affective information processing as assessed by means of our established 50-kHz USV radial maze playback paradigm. We showed that post-weaning social isolation specifically affected the behavioral response to playback of pro-social 50-kHz but not alarm 22-kHz USV. While group-housed rats showed the expected preference, i.e., approach, toward 50-kHz USV, the response was even stronger in short-term isolated rats (i.e., 1 day), possibly due to a higher level of social motivation. In contrast, no approach was observed in long-term isolated rats (i.e., 4 weeks). Importantly, deficits in approach were reversed by peer-mediated re-socialization and could not be observed after post-adolescent social isolation, indicating a critical period for social development during adolescence. Together, these results highlight the importance of social experience for affiliative behavior, suggesting a critical involvement of play behavior on socio-affective information processing in rats.

The dopamine D 3 -preferring D 2 /D 3 dopamine receptor partial agonist, cariprazine, reverses behavioural changes in a rat neurodevelopmental model for schizophrenia

“…The USVs recorded in all groups were in the 50kHz range which occur in social, appetitive situations, during tickling and sexual behaviour thought to reflect positive affective state in rats (Brudzynski, 2013;Seffer et al, 2015). The increase in USVs in the socially isolated rats may reflect an increased motivation for social interaction although this was not accompanied by an increase in total social interaction compared to group-housed rats.…”

“…Consistent with the current findings the increase in avoidance and decrease in following behaviour produced by sub-chronic PCP administration to adult rats was also reversed by cariprazine (Neill et al, 2015). Using an identical PCP/isolate paradigm we found that clozapine (at doses which reversed the NOR deficit) was unable to restore the pro-social behavioural deficit (McIntosh et al, 2012), consistent with clozapine's limited efficacy to treat the negative symptoms of schiziophrenia and supporting the potential translational value of this test.The USVs recorded in all groups were in the 50kHz range which occur in social, appetitive situations, during tickling and sexual behaviour thought to reflect positive affective state in rats (Brudzynski, 2013;Seffer et al, 2015). The increase in USVs in the socially isolated rats may reflect an increased motivation for social interaction although this was not accompanied by an increase in total social interaction compared to group-housed rats.…”

Modulation of long interspersed nuclear element-1 in the mouse hippocampus during maturation

“…To exclude the effects of contaminated RNA-hybiridsed L1 DNA, 22 we re-evaluated copy numbers of L1-ORF2 after treating DNA samples with RNaseH and exonuclease 1, but obtained similar results (Mann-Whitney U test, ORF2 / 5S rDNA: P D 0.02, ORF2 / b-globin: P D 0.01, Figure S1). Additional analysis of the DNA samples of mice at 15,18,20, and »55 weeks after birth indicated that the L1 copy numbers were maximal at 8 weeks after birth (Fig. 1A, left panel).…”

“…To study chronological changes in the L1-ORF2 copy numbers, 6 groups of mice at various ages (3,8,15,18,20, and »55 weeks) were analyzed. Six mice from each group (3 males and 3 females) and 6 8-week-old mice used for validation (3 males and 3 females) were deeply anaesthetised and perfused transcardially with cold 4% paraformaldehyde in phosphate-buffered saline (PBS), and genomic DNA was extracted from the right and left hippocampi and the prefrontal cortex.…”

“…[11][12][13][14][15][16] Generally, SI stress impairs neuronal precursor cells at multiple steps, including the mitotic and survival phases of neurogenesis. 17 SI also suppresses the expression of glutamate receptor, 18 which functions in learning and memory.…”