ABSTRACT
Drug exposure during adolescence, when the "reward" circuitry of the brain is developing, can permanently impact reward-related behavior into adulthood. Epidemiological studies show that opioid treatment during adolescence, such as pain management for a dental procedure or surgery, increases the incidence of psychiatric illness including substance use disorders. Moreover, the opioid epidemic currently in the United States is affecting younger individuals raising the impetus to understand the pathogenesis of the negative effects of opioids. One reward-related behavior that develops during adolescence is social behavior. We previously demonstrated that developmental changes in the nucleus accumbens reward region regulate social development in rats during sex-specific adolescent periods: early to mid-adolescence in males (postnatal day, P30-40) and preearly adolescence in females (P20-30). We thus hypothesized that the developmental stage of morphine exposure will differentially impact social behavior development such that drug administered during the female critical period would result in adult sociability deficits in females, but not males, and morphine administered during the male critical period would result in adult sociability deficits in males, but not females. We found that morphine exposure during the female critical period primarily resulted in deficits in sociability in females, while morphine exposure during the male critical period primarily resulted in deficits in sociability primarily in males. However, depending on the test performed and the social parameter measured, social alterations could be found in both sexes that received morphine exposure at either adolescent stage. These data indicate that when drug exposure occurs during adolescence, and how the endpoint data are measured, will play a large role in determining the effects of drug exposures on social development. (PsycInfo Database Record (c) 2024 APA, all rights reserved).
Subject(s)
Morphine , Social Change , Rats , Female , Male , Animals , Morphine/pharmacology , Analgesics, Opioid/pharmacology , Social Behavior , Nucleus AccumbensABSTRACT
Strong social support promotes a variety of positive health outcomes in humans and rodent models, while social isolation in rodents shortens lifespan, perceived social isolation (i.e. loneliness) can increase mortality by up to 50% in humans. How social relationships lead to these drastic health effects is unclear, but may involve modulation of the peripheral immune system. The reward circuitry of the brain and social behaviors undergo a critical period of development during adolescence. We published that microglia-mediated synaptic pruning occurs in the nucleus accumbens (NAc) reward region during adolescence to mediate social development in male and female rats. We hypothesized that if reward circuitry activity and social relationships directly impact the peripheral immune system, then natural developmental changes in the reward circuitry and social behaviors during adolescence should also directly impact the peripheral immune system. To test this, we inhibited microglial pruning in the NAc during adolescence, and then collected spleen tissue for mass spectrometry proteomic analysis and ELISA validation. We found that the global proteomic consequences of inhibiting microglial pruning in the NAc were similar between the sexes, but target-specific examination suggests that NAc pruning impacts Th1 cell-related immune markers in the spleen in males, but not females, and broad neurochemical systems in the spleen in females, but not males.
ABSTRACT
Adolescence is a period of copious neural development, particularly in the 'reward' circuitry of the brain, and reward-related behavioral development, including social development. One neurodevelopmental mechanism that appears to be common across brain regions and developmental periods is the requirement for synaptic pruning to produce mature neural communication and circuits. We published that microglia-C3-mediated synaptic pruning also occurs in the nucleus accumbens (NAc) reward region during adolescence to mediate social development in male and female rats. However, both the adolescent stage in which microglial pruning occurred, and the synaptic pruning target, were sex specific. NAc pruning occurred between early and mid-adolescence in male rats to eliminate dopamine D1 receptors (D1rs), and between pre- and early adolescence in female rats (P20-30) to eliminate an unknown, non-D1r target. In this report, we sought to better understand the proteomic consequences of microglial pruning in the NAc, and what the female pruning target might be. To do this, we inhibited microglial pruning in the NAc during each sex's pruning period and collected tissue for mass spectrometry proteomic analysis and ELISA validation. We found that the proteomic consequences of inhibiting microglial pruning in the NAc were inversely proportional between the sexes, and a novel, female-specific pruning target may be Lynx1. Please note, if this preprint will be pushed further to publication it will not be by me (AMK), as I am leaving academia. So, I'm going to write more conversationally.
ABSTRACT
Social networks and support are integral to health and wellness across the lifespan, and social engagement may be particularly important during aging. However, social behavior and social cognition decline naturally during aging across species. Social behaviors are in part supported by the 'reward' circuitry, a network of brain regions that develops during adolescence. We published that male and female rats undergo adolescent social development during sex-specific periods, pre-early adolescence in females and early-mid adolescence males. Although males and females have highly dimorphic development, expression, and valuation of social behaviors, there is relatively little data indicating whether social aging is the same or different between the sexes. Thus, we sought to test two hypotheses: (1) natural social aging will be sex-speciifc, and (2) social isolation stress restricted to sex-specific adolescent critical periods for social development would impact social aging in sex-specific ways. To do this, we bred male and female rats in-house, and divided them randomly to receive either social isolation for one week during each sex's respective critical period, or no manipulation. We followed their social aging trajectory with a battery of five tests at 3, 7, and 11 months of age. We observed clear social aging signatures in all tests administered, but sex differences in natural social aging were most robustly observed when a familiar social stimulus was included in the test. We also observed that adolescent isolation did impact social behavior, in both age-independent and age-dependent ways, that were entirely sex-specific. Please note, this preprint will not be pushed further to publication (by me, AMK), as I am leaving academia. So, it's going to be written more conversationally.
ABSTRACT
Drug exposure during adolescence, when the 'reward' circuitry of the brain is developing, can permanently impact reward-related behavior. Epidemiological studies show that opioid treatment during adolescence, such as pain management for a dental procedure or surgery, increases the incidence of psychiatric illness including substance use disorders. Moreover, the opioid epidemic currently in the United States is affecting younger individuals raising the impetus to understand the pathogenesis of the negative effects of opioids. One reward-related behavior that develops during adolescence is social behavior. We previously demonstrated that social development occurs in rats during sex-specific adolescent periods: early to mid-adolescence in males (postnatal day (P)30-40) and pre-early adolescence in females (P20-30). We thus hypothesized that morphine exposure during the female critical period would result in adult sociability deficits in females, but not males, and morphine administered during the male critical period would result in adult sociability deficits in males, but not females. We found that morphine exposure during the female critical period primarily resulted in deficits in sociability in females, while morphine exposure during the male critical period primarily resulted in deficits in sociability primarily in males. However, depending on the test performed and the social parameter measured, social alterations could be found in both sexes that received morphine exposure at either adolescent stage. These data indicate that when drug exposure occurs during adolescence, and how the endpoint data are measured, will play a large role in determining the effects of drug exposures on social development.
