Decreased tryptophan hydroxylase 2 mRNA and protein expression, decreased brain serotonin concentrations, and anxiety-like behavioral changes in a rat model of simulated transport stress

Transport stress causes not only physiological changes but also behavioral responses, including anxiety-like and depression-like behaviors in animals. The serotonergic system in the brain plays a pivotal role in processing anxiety. This study aimed to explore changes in concentrations of 5-hydroxytryptamine (serotonin), and the expression changes of tryptophan hydroxylase 2 (TPH2) mRNA and protein associated with anxiety-related behavioral responses under transport stress. A model of simulated transport stress was established in 40 adult male Sprague-Dawley rats, including a control group (n = 20) and a transport stress (TS) group (n = 20). The results showed that the rats in the TS group exhibited an increased feeding latency in the novelty-suppressed feeding test and a reduced frequency and dwelling time in the central area in the open-field test (OFT). Two hours following the final behavioral test, blood samples were collected. Creatine kinase (CK) activities and glucose and corticosterone concentrations in serum were significantly higher in the rats in the TS group than in the control group. Transport stress also significantly reduced the concentrations of 5-hydroxytryptamine in the hippocampus, striatum, and raphe nuclei and also reduced the expression levels of mRNA and protein for TPH2 in the raphe nuclei. Notably, the number of Fos-immunoreactive neurons was higher in the dorsal raphe nucleus under transport stress, whereas the number of 5-hydroxytryptamine-positive neurons was significantly lower. These findings are consistent with the hypothesis that the 5-hydroxytryptamine transmitter in the hippocampus, striatum, and raphe nuclei is involved in processing anxiety-related behavioral responses under transport stress.Lay summary Physiological and psychological stress responses were induced in a rat model of simulated transport stress. We examined whether serotonin in the brain may be involved in mediating behavioral responses following exposure to transport stress. Tissue concentrations of serotonin in rat brain regions, including the hippocampus, striatum, and raphe nuclei, were reduced following exposure to transport stress. Expression of tryptophan hydroxylase 2 mRNA and protein, which catalyses serotonin synthesis, as well as numbers of serotonin-immunoreactive neurons, were decreased in the brainstem raphe nuclei.