Changes in gut microbiota during development of compulsive checking and locomotor sensitization induced by chronic treatment with the dopamine agonist quinpirole

Abstract

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.

The gut microbiome and inflammation in obsessive‐compulsive disorder patients compared to age‐ and sex‐matched controls: a pilot study

“…A recent study of an OCD animal model using a dopamine agonist (quinpirole) revealed that onset of locomotor sensitivity and compulsive checking (OCD‐like behaviours) were associated with changes in OTUs from the Lachnospiraceae and Ruminococcaceae family (40). Odoribacter, Oscillospira and Anaerostipes also belong to the same taxonomic families.…”

“…Odoribacter, Oscillospira and Anaerostipes also belong to the same taxonomic families. It was suggested that these gut microbiota are likely related to dopamine activity (40), as two studies in patients with Parkinson's disease (41,42) and another using a dopamine agonist in rats (43) revealed alterations of OTUs in the same family. Similarly, Quagliariello et al (2018) (8) reported that levels of Bacteroides , Odoribacter and Oscillospira were higher in the younger (ages 4–8 years vs. age 9) PANS group than in controls.…”

Methamphetamine Disturbs Gut Homeostasis and Reshapes Serum Metabolome, Inducing Neurotoxicity and Abnormal Behaviors in Mice

“…Locomotor sensitization has also been shown to be closely associated with gut microbiota. In rodent models, quinpirole-induced locomotor sensitization was accompanied by microbial dysbiosis ( Jung et al, 2018 ). Furthermore, antibiotic-mediated microbial reduction showed an enhanced sensitivity to cocaine-induced locomotor sensitization ( Kiraly et al, 2016 ).…”

What Does Immunology Have to Do With Normal Brain Development and the Pathophysiology Underlying Tourette Syndrome and Related Neuropsychiatric Disorders?

“…Pharmacological animal models expressing compulsive behaviors revealed an association between the behavioral phenotype and changes in gut microbial communities. Chronic quinpirole injections in rats induced locomotor sensitization and compulsive checking associated with changes in abundance of Firmicutes, predominantly Lachnospiraceae and Ruminococcaceae (224). Another study demonstrated different gut microbiota composition between the naturally occurring obsessive-compulsive and the normal phenotypes of deer mice (225).…”