Serotonin1A receptor deletion does not interact with maternal separation-induced increases in startle reactivity and prepulse inhibition deficits

Abstract

RationaleEarly life stress is a risk factor for the development of psychopathology in later life. Consequences of adverse life events, however, may depend on the genetic makeup of an individual. Reduced serotonin1A receptor function may predispose to the development of anxiety disorders.ObjectiveDetermine susceptibility of serotonin1A receptor knockout (1AKO) mice on different background strains to the effects of maternal separation (MS) by assessing startle plasticity in adulthood.Methods1AKO mice on a 129S6 and a Swiss Webster (SW) background were used. MS groups were separated daily from their mother for 180 min/day from postnatal days 2 to 14. Control groups underwent normal animal facility rearing. In adulthood, effects on acoustic startle response, habituation, prepulse inhibition (PPI), and foot shock sensitization were determined.ResultsMS increased startle reactivity and reduced PPI in 129S6 mice. These effects of MS were independent of genotype. MS had no effect on the other readouts. In SW mice, MS had no consistent effect on startle reactivity and did not alter startle plasticity in wild type or in 1AKO mice. 1AKO mice did not differ from wild-type mice in startle plasticity.ConclusionSerotonin1A receptor deletion does not enhance vulnerability to the effects of MS on startle plasticity. The life-long increase in startle reactivity and PPI deficit induced by MS are strain-dependent. Further, the use of startle reactivity and plasticity may have added value in translational studies relating to early life stress.

Mgat5 modulates the effect of early life stress on adult behavior and physical health in mice

“…For example, deletion of the serotonin 1A receptor does not [56], demonstrating the importance of identifying the specific gene-environment interactions that affect resilience. Interestingly, Mgat5 -/-first-time mothers housed alone displayed less time gathering pups and nurturing whereas two Mgat5 -/-mothers housed together were more efficient at rearing pups as measured by survival [40].…”

Linking Stress and Schizophrenia: A Focus on Prepulse Inhibition

“…Also, methodological factors such as timing, duration, and number of deprivation episodes, could possibly explain a lack of effect of maternal deprivation (Ellenbroek & Cools, 2002). Thereby, the ability of maternal separation to produce PPI-disrupting effects appears to be dependent on genetic strain (Ellenbroek & Cools, 2000), and species under study (rat vs. mouse) (Millstein & Holmes, 2007;Groenink et al, 2011;Naert et al, 2011). Thus, maternal separation seems to induce PPI-deficits in a delayed fashion; however, the effect could be influenced by various protecting or facilitating post-deprivational factors, which might be similar to the influence of early-life stressors in humans.…”

“…Douma, M.J. Millan, B. Olivier and L. Groenink (2011). Linking Stress and Schizophrenia: A Focus on Prepulse Inhibition, Psychiatric Disorders -Trends and Developments, Dr. Toru Uehara (Ed.…”

Interactions between corticotropin-releasing factor and the serotonin 1A receptor system on acoustic startle amplitude and prepulse inhibition of the startle response in two rat strains

“…PPI is equivalent in 5-HT 1A receptor knockout and wild-type mice (Dirks et al, 2001). Additionally, maternal separation-induced increases in startle amplitude and decreases in PPI are not attenuated by deletion of the 5-HT 1A receptor (Groenink et al, 2011). Never-the-less, 8-OH-DPAT does have effects on PPI in mice.…”