Long-term treatment of rats with the D2/D3 dopamine agonist quinpirole induces compulsive checking (proposed as animal model of obsessive-compulsive disorder) and locomotor sensitization. The mechanisms by which long-term use of quinpirole produces those behavioral transformations are not known. Here we examined whether changes in gut microbiota play a role in these behavioral phenomena, by monitoring the development of compulsive checking and locomotor sensitization at the same time as measuring the response of gut microbiota to chronic quinpirole injections. Two groups of rats received nine injections of saline (n=16) or quinpirole (n=15; 0.25 mg/kg), at weekly intervals for the first 5 weeks and then two injections per week until the end of treatment. After each injection, rats were placed on a large open field for 55 min, and their behavior was video recorded for subsequent analysis. Fecal matter was collected after each trial and frozen for bacterial community profiling of the 16S rRNA gene, using paired-end reads of the V3 region. The results indicated that the induction of locomotor sensitization and compulsive checking was accompanied by changes in several communities of bacteria belonging to the order Clostridiales (class Clostridia, phylum Firmicutes), and predominantly in Lachnospiraceae and Ruminococcaceae families of bacteria. It is suggested that changes in these microbes may serve to support the energy use requirements of compulsive checking and obsessive-compulsive disorder.

It is not known why there is increased risk to have seizures with increased anxiety and stress after traumatic brain injury (TBI). Stressors cause the release of corticotropin-releasing factor (CRF) both from the hypothalamic pituitary adrenal (HPA) axis and from CNS neurons located in the central amygdala and GABAergic interneurons. We have previously shown that CRF signaling is plastic, becoming excitatory instead of inhibitory after the kindling model of epilepsy. Here, using Sprague Dawley rats we have found that CRF signaling increased excitability after TBI. Following TBI, CRF type 1 receptor (CRFR 1 )-mediated activity caused abnormally large electrical responses in the amygdala, including fast ripples, which are considered to be epileptogenic. After TBI, we also found the ripple (120–250 Hz) and fast ripple activity (>250 Hz) was cross-frequency coupled with θ (3–8 Hz) oscillations. CRFR 1 antagonists reduced the incidence of phase coupling between ripples and fast ripples. Our observations indicate that pathophysiological signaling of the CRFR 1 increases the incidence of epileptiform activity after TBI. The use for CRFR 1 antagonist may be useful to reduce the severity and frequency of TBI associated epileptic seizures.