A single dose of ketamine cannot prevent protracted stress-induced anhedonia and neuroinflammation in rats

Social adversity during juvenile age but not adulthood increases susceptibility to an immune challenge later in life

“…Non-invasive [ 11 C]PBR28 PET imaging revealed that LPS injection alone increased TSPO levels, a protein associated with microglial reactivity in several brain regions, such as the frontal cortex, striatum, and brainstem. In accordance with other studies ( Moraga-Amaro et al, 2022 ; Rodríguez-Arias et al, 2018 ), s ocial stress during juvenile age or adulthood induced a long-lasting increase in reactive microglia in brain regions related to stress-induced psychopathologies, such as the frontal cortex, striatum, brainstem and hippocampus. This result is in line with human studies that observed a link between early life stress characterized as childhood maltreatment and being raised in a ‘harsh family’ and heightened peripheral and central markers of inflammation ( Danese and J Lewis, 2017 ; Miller and Chen, 2010 ).…”

“…However, our RSD model did not induce anxiety-like behavior, altered locomotion, or social dysfunction, as the time spent in the center of the open field, the distance travelled, and the social interaction were not affected. Previous studies using the RSD protocol during juvenile age or adulthood have shown contradictory results, as either an increase in anxiety and social dysfunction ( MacKay et al, 2017 ; Mancha-Gutiérrez et al, 2021 ; Mancini et al, 2021 ), or no effect ( Moraga-Amaro et al, 2022 ; Mouri et al, 2018 ) have been reported. Many factors may explain such differences, including housing conditions, differences in the RSD procedure, its duration and timing, and the interval between the RSD and the behavioral tests.…”

“…To encourage territoriality, each male resident was housed in a large cage (80*50*40 cm) with an ovariectomized female Long Evans rat that underwent tubal ligation for at least one week before the screening. The screening consisted of measuring attack latency and submission time in RSD sessions on five consecutive days to select rats displaying the desired aggressive behavior and exclude rats showing signs of violence (attack latency <10 s and attempts to kill the intruder by attacking vital zones), or non-aggressive behavior (attack latency>60s, absence of submission or submission time >120s, or the resident being submitted) ( Moraga-Amaro et al, 2022 ).…”

Impact of stress on inhibitory neuronal circuits, our tribute to Bruce McEwen

“…Both clinical and animal studies demonstrated that a single dose of ketamine provoked anti-depressant effects ( Autry et al, 2011 ; Berman et al, 2000 ; Li et al, 2010 ). In this line, ketamine disrupted the inflammation associated with repeated social stress in adult rats ( Moraga-Amaro et al, 2022 ) and blocked the acute stress-induced enhancement of glutamate release at different time-points after a footshock in adult rats ( Sala et al, 2022 ). Ketamine also rescued the dendritic retraction of pyramidal neurons induced by acute stress in the PFC ( Sala et al, 2022 ).…”