No abstract

The mechanisms underlying chronic psychiatric-like impairments after traumatic brain injury (TBI) are currently unknown. The goal of the present study was to assess the role of diet and the gut microbiome in psychiatric symptoms after TBI. Rats were randomly assigned to receive a high-fat diet (HFD) or caloriematched low-fat diet (LFD). After 2 weeks of free access, rats began training on the rodent gambling task (RGT), a measure of risky decision-making and motor impulsivity. After training, rats received a bilateral frontal TBI or a sham procedure and continued postinjury testing for 10 weeks. Fecal samples were collected before injury and 3-, 30-, and 60 days postinjury to evaluate the gut microbiome. HFD altered the microbiome, but ultimately had low-magnitude effects on behavior and did not modify functional outcomes after TBI. Injury-induced functional deficits were far more robust; TBI substantially decreased optimal choice and increased suboptimal choice and motor impulsivity on the RGT. TBI also affected the microbiome, and a model comparison approach revealed that bacterial diversity measured 3 days postinjury was predictive of chronic psychiatric-like deficits on the RGT. A functional metagenomic analysis identified changes to dopamine and serotonin synthesis pathways as a potential candidate mechanism. Thus, the gut may be a potential acute treatment target for psychiatric symptoms after TBI, as well as a biomarker for injury and deficit severity. However, further research will be needed to confirm and extend these findings.

In two experiments, pigeons were exposed to a three-phase resurgence procedure (train Response A; extinguish Response A and train Response B; extinguish Response B). In the first experiment, the stimuli associated with phases were different, resulting in a resurgence procedure combined with an ABC renewal procedure. Presenting the novel stimulus, C, during extinction of both responses in the third phase resulted in minimal resurgence. Subsequently, substituting the original training Stimulus A for Stimulus C resulted in resurgence with all pigeons. In the second experiment, resurgence with the same stimuli present in all three phases of the resurgence procedure (AAA) was compared concurrently with a resurgence procedure in which the ABC renewal procedure used in Experiment 1 was superimposed. Substantially more resurgence occurred with the AAA procedure compared to the ABC procedure. Although ABC renewal in combination with the resurgence procedure generated some resurgence, such recurrent responding was attenuated relative to that observed when the stimulus conditions were constant across phases. Combined with earlier research showing the enhancing effects of combining resurgence and ABA renewal procedures, the present results elaborate on how stimuli correlated with certain behavioral histories affect the course of operant resurgence.

No abstract

Depression is the most common psychiatric comorbidity to be diagnosed following traumatic brain injury (TBI). In clinical populations, TBI-induced depression may be particularly difficult to treat due to both unique underlying causes and the propensity for treatment resistance. Preclinical assays are needed to characterize depressive-like behavior in models of TBI and evaluate treatments. In the current study, two traditionally-acute assays of depressive-like behaviors, the Forced Swim Task and Saccharin Preference, were extended longitudinally to evaluate chronic TBI-induced depressive-like behaviors in male rats. Two chronic measures of motivation, the Progressive Ratio (PR) task and Effort Discounting Task (EDT), were also tested. The PR measures motivation to exert effort, while the EDT parametrically evaluates choice between lowand high-effort requirements. The EDT was the only assay which captured chronic depressive-like behavior after TBI, albeit with a degree of recovery over time. We found that traditionally-acute measures (Forced Swim Task, Saccharin Preference), and even our other chronic measure (PR), failed to capture long-term deficits. We also challenged serotonin and dopamine systems (via fluoxetine and bupropion) to evaluate how TBI-induced changes to these systems might drive depressive-like behaviors. Although we found no effect of fluoxetine, high-dose bupropion differentially impaired TBI rats. These findings suggest that (1) TBI-induced depressive symptoms remain difficult to measure at the preclinical level, (2) treatment for TBI-induced depression requires further exploration, and (3) obstacles at the preclinical level may translate to treatment failure at the clinical level.