Short post‐weaning social isolation induces long‐term changes in the dopaminergic system and increases susceptibility to psychostimulants in female rats

Abstract

Childhood and adolescence are sensitive periods of development, marked by high brain maturation and plasticity. Exposure to early life stress, such as social isolation, is able to prompt changes in sensitive brain circuitries, essentially in the mesolimbic dopaminergic system and increase the risk for addictive behaviors later in life. Post-weaning social isolation can stimulate the consumption of rewarding substances, like drugs of abuse and palatable foods. However, most studies analyze long periods of social isolation and very little is known about the effects of a brief social isolation in a sensitive period of development and its association with palatable food on the reward system sensitization. Furthermore, females are more susceptible to the reinforcing effect of drugs than males. Therefore, the aim of this study was to analyze the effects of a short post-weaning social isolation combined with a free access to a chronic high sugar diet (HSD) on the dopaminergic system, oxidative status and behavioral response to an amphetamine-like drug in adulthood. We used female Wistar rats that were socially isolated from post-natal days (PD) 21 to 35 and received free access to a HSD until PD 60. On PD 65, animals were submitted to a challenge with diethylpropion (DEP), an amphetamine-like drug and different responses were analyzed: locomotor activity, immmunocontent of dopamine related proteins, and the oxidative status in the striatum, before and after the DEP challenge. We showed that a short post-weaning social isolation (SI) increased the locomotor response to DEP, when compared with previous saline administration. Social isolation also increased dopamine transporter, tyrosine hydroxylase, and decreased dopamine D2 receptor immunocontent. Additionally, SI increased the overall oxidative status parameters after the challenge with DEP. Interestingly, the exposure to a HSD prevented the SI effects on locomotor response, but did not interfere in the dopaminergic parameters evaluated, despite having modified some oxidative parameters. This study showed for the first time that a short post-weaning social isolation was able to induce long-term changes in the striatal dopaminergic system and increased the response to psychostimulants. These results emphasize the importance of stressful experiences during a short period of development on programming susceptibility to psychostimulants later in life.

Chronic Social Isolation Stress during Peri-Adolescence Alters Presynaptic Dopamine Terminal Dynamics via Augmentation in Accumbal Dopamine Availability

“…The peri-adolescent period during which we expose the rats to social isolation is rather long, and there may be a narrow window that could produce some of the phenotypes that we study. , We chose a longer isolation period in the current study to be consistent with our earlier studies, which revealed profound and enduring behavioral and neurobiological adaptations using this model. In addition, in a previous study we showed that social isolation during adulthood does not affect electrically stimulated dopamine release and uptake measures .…”

Early Life Stress and Risks for Opioid Misuse: Review of Data Supporting Neurobiological Underpinnings

“…Considerable preclinical evidence has emerged showing that ELS may lead to profound and long-term derangements in brain DA neurotransmission. Abnormalities that have been observed include but are not limited to altered D1, D2, and D3 receptor mRNA expression; decreased density of DA transporters; increased DA metabolites in the striatum and/or NAc [289][290][291][292][293][294]; and reduced rates of DA clearance in the mPFC [295]. Both enhanced [290,296,297] and blunted [290,[296][297][298] striatal DA responses to stress have been observed in adult rodents exposed to ELS.…”

COVID-19 pandemic impact on children and adolescents' mental health: Biological, environmental, and social factors

“…Furthermore, it has been shown that a short period of social isolation during adolescence is able to induce long-term effects on dopaminergic pathways in rats ( Lampert et al, 2017 ). However, a high-fat diet has controversial results on the dopaminergic pathways due, in part, to different dietary lipid compositions.…”