Evaluation of the Effects of Developmental Trauma on Neurotransmitter Systems Using Functional Molecular Imaging

Abstract

Early life stress (ELS) is strongly associated with psychiatric disorders such as anxiety, depression, and schizophrenia in adulthood. To date, biological, behavioral, and structural aspects of ELS have been studied extensively, but their functional effects remain unclear. Here, we examined NeuroPET studies of dopaminergic, glutamatergic, and serotonergic systems in ELS animal models. Maternal separation and restraint stress were used to generate single or complex developmental trauma. Body weights of animals exposed to single trauma were similar to those of control animals; however, animals exposed to complex trauma exhibited loss of body weight when compared to controls. In behavioral tests, the complex developmental trauma group exhibited a decrease in time spent in the open arm of the elevated plus-maze and an increase in immobility time in the forced swim test when compared to control animals. In NeuroPET studies, the complex trauma group displayed a reduction in brain uptake values when compared to single trauma and control groups. Of neurotransmitter systems analyzed, the rate of decrease in brain uptake was the highest in the serotonergic group. Collectively, our results indicate that developmental trauma events induce behavioral deficits, including anxiety- and depressive-like phenotypes and dysfunction in neurotransmitter systems.

Effect of developmental stress on the in vivo neuronal circuits related to excitation–inhibition balance and mood in adulthood

“…In addition, since only restraint stress was used for a single trauma in the present study, the effect of other traumatic events is unknown. Our previous work has demonstrated that there is no significant difference between the two groups when evaluated in adulthood, after imposing single stressors such as MS or restraint stress during the developmental periods (17). However, sexual differences in MS were not explained because the study used only males.…”

“…Rats were tested in an elevated plus-maze according to previously described procedures (17). The apparatus was made of acrylic and consisted of two closed arms with walls (40 cm × 10 cm × 30 cm) and two open arms (40 cm × 10 cm) connected by an open central platform (10 cm × 10 cm).…”

“…This test was performed as previously described (17). Rats were placed in acrylic cylinders (20 cm diameter × 45 cm height) filled with fresh water (35 ±1 cm), and water temperature was maintained at 25 ±1 • C. Rats were forced to swim for 15 min on the day before the test.…”

“…[ 18 F]flumazenil, [ 18 F]FPEB, and [ 18 F]Mefway are specific radiotracers for GABAergic (i.e., GABA A receptor), glutamatergic (i.e., mGluR5), and serotonergic systems (i.e., 5-HT 1A receptor), respectively. The radiotracers were prepared according to a previously described procedure (17,18). The radiochemical purity of all radiotracers at the end of the synthesis was over 95%.…”

Effects of Maternal Separation and Subsequent Stress on Behaviors and Brain Monoamines in Rats

“…We expected that early-life abuse would lead to attachment disorder in rat pups and to formation in later life of persistent neurobehavioral deficits not associated with the development of depression-like phenotype. It was shown that more pronounced disorders in behavior and neurotransmission were observed in rats subjected to complex aversive influences during brain development [ 62 , 63 ].…”