Adolescent stress during, but not after, pubertal onset impairs indices of prepulse inhibition in adult rats

Abstract

Exposure to stress during adolescence is a risk factor for developing several psychiatric disorders, many of which involve prefrontal cortex (PFC) dysfunction. The human PFC and analogous rodent medial prefrontal cortex (mPFC) continue to mature functionally and anatomically during adolescence, and some of these maturational events coincide with pubertal onset. As developing brain regions are more susceptible to the negative effects of stress, this may make puberty especially vulnerable. To test this, we exposed male and female rats to isolation and restraint stress during the onset of puberty or during the post-pubertal period of adolescence. In young adulthood, both stressed groups and an unstressed control group underwent testing on a battery of tasks to assess emotional and cognitive behaviors, and the volume of the mPFC was quantified postmortem. Factor analysis revealed only subjects stressed peripubertally showed a long-term deficiency compared to controls in prepulse inhibition.Additionally, both sexes showed volumetric mPFC decreases following adolescent stress, and these losses were most pronounced in females. Our findings suggest that pubertal onset may be a vulnerable window wherein adolescents are most susceptible to the negative consequences of stress exposure. Furthermore, it highlights the importance of accounting for pubertal status when studying adolescents.

Timing of methamphetamine exposure during adolescence differentially influences parvalbumin and perineuronal net immunoreactivity in the medial prefrontal cortex of female, but not male, rats

“…Another example of differential timing comes from work on pre-pulse inhibition (PPI), a task that relies on the mPFC [41,42]. PPI is deficient in females that experienced daily restraint stress during early, but not late, adolescence [22]. Interestingly, PPI was also deficient in males when the stress was applied peri-pubertally which coincides with late adolescence in the present study, and males were not affected even later, but post-pubertal, in adolescence.…”

“…This all suggests that adolescence may be a time of increased negative consequences of stimulant use, particularly for females, which coincides with the development of PV neurons and PNNs in the mPFC. Timing of exposure within adolescence may also be important since many structural changes occur around female puberty [10, 21], and both sexes are behaviorally more sensitive to stress peri-pubertally in adolescence [22].…”

Looming Effects on Attentional Modulation of Prepulse Inhibition Paradigm

“…It has been further suggested that the PFC mediates the attentional enhancement of PPI of the acoustic startle reflex ( Meng et al, 2020 ). Additionally, prefrontal dysfunction caused by isolation stress during adolescence resulted in PPI deficits ( Drzewiecki et al, 2021 ; Du et al, 2021 ). What other brain areas are involved in and how the brain network subserving attention is involved in this process need further investigation.…”

The last stage of development: The restructuring and plasticity of the cortex during adolescence especially at puberty

“…Both peri-pubertal stressed males and females have lower PPI scores (less sensorimotor gating) than control and post-pubertal stressed rats. *p < .05, ***p < .001 (Drzewiecki, Willing et al, 2021).…”

“…This occurred in parallel in both sexes in spite of a main effect of sex such that females had lower PPI scores than males. It is also notable that the age of the post-pubertal females overlapped the age of the peripubertal males (Drzewiecki, Willing et al, 2021).…”