Maternal separation and TNBS-induced gut inflammation synergistically alter the sexually differentiated stress response in rats.

BACKGROUND: Neonatal maternal separation (MS) has been used to model long-lasting changes in behavior caused by neuroplastic changes associated with exposure to early-life stress. Earlier studies showed that transient gut inflammation can influence the development of irritable bowel syndrome (IBS). A prevailing paradigm of the etiology of IBS is that transient noxious events lead to long-lasting sensitization of the neural pain circuit, despite complete resolution of the initiating event. This study characterizes the changes in behaviors and neuroendocrine parameters after MS and early-phase trinitrobenzene sulfonic acid (TNBS)-induced colitis. We tested the hypothesis that MS and gut inflammation synergistically induce (1) hyperactivity in male rats and anxiety-like behaviors in female rats and (2) activation of the HPA axis in female rats and deactivation of the HPA axis in male rats after colorectal distention (CRD). METHODS: Male and female rat pups were separated from their dams for 180 min daily from postnatal day (PND) 2 to PND 14 (MS). Early-phase colitis was induced by colorectal administration with TNBS on PND 8. The elevated plus-maze test was performed at 7 weeks. Tonic CRD was performed at 60 mmHg for 15 min at 8 weeks. Plasma ACTH and serum corticosterone were measured at baseline or after the CRD. Analysis of variance was performed for comparison among controls, TNBS, MS, and MS + TNBS. RESULTS: In male rats, the time spent in open arms significantly differed among the groups (p < 0.005). The time spent in open arms in male MS + TNBS rats was significantly higher than that of controls (p < 0.009) or TNBS rats (p < 0.031, post hoc test). Female rats showed no difference in the time spent in open arms among the groups. MS and gut inflammation induced an increase in plasma ACTH in female rats but not in male rats at baseline. CONCLUSIONS: These findings suggest that MS and gut inflammation synergistically induce hyperactive behavior or exaggerated hypothalamic-pituitary-adrenal axis function depending on sex.

Dai-Kenchu-To, a Herbal Medicine, Attenuates Colorectal Distention-induced Visceromotor Responses in Rats.

BACKGROUND/AIMS: Dai-kenchu-to (DKT), a traditional Japanese herbal medicine, is known to increase gastrointestinal motility and improve ileal function. We tested our hypotheses that (1) pretreatment with DKT would block the colorectal distention-induced visceromotor response in rats, and (2) pretreatment with DKT would attenuate colorectal distention-induced adrenocorticotropic hormone (ACTH) release and anxiety-related behavior. METHODS: Rats were pretreated with vehicle or DKT (300 mg/kg/5 mL, per os). Visceromotor responses were analyzed using electromyography in response to colorectal distention (10, 20, 40, 60, and 80 mmHg for 20 seconds at 3-minutes intervals). Anxiety-related behavior was measured during exposure to an elevated-plus maze after colorectal distention. Plasma ACTH and serum corticosterone levels were measured after exposure to the elevated-plus maze. RESULTS: Colorectal distention produced robust contractions of the abdominal musculature, graded according to stimulus intensity, in vehicle-treated rats. At 40, 60, and 80 mmHg of colorectal distention, the visceromotor responses of DKT-treated rats was significantly lower than that of vehicle-treated rats. At 80 mmHg, the amplitude was suppressed to approximately one-third in DKT-treated rats, compared with that in vehicle-treated rats. Smooth muscle compliance and the velocity of accommodation to 60 mmHg of stretching did not significantly differ between the vehicle-treated and DKT-treated rats. Similarly, the DKT did not influence colorectal distention-induced ACTH release, corticosterone levels, or anxiety-related behavior in rats. CONCLUSIONS: Our results suggest that DKT attenuates the colorectal distention-induced visceromotor responses, without increasing smooth muscle compliance, ACTH release or anxiety-related behavior in rats.

A Japanese scale to assess anxiety severity: development and psychometric evaluation.

OBJECTIVE: This study developed a Japanese self-rating anxiety scale, the Himorogi Self-rating Anxiety Scale (HSAS), and tested psychometric properties of its use in Japanese psychiatric patients. METHODS: The process of developing the scale consisted of an intensive literature review, assessment of existing instruments, and detailed discussion on the content of the newly developed scale. Data for psychometric evaluation were collected from 419 outpatients of psychiatric clinics. The Hamilton Rating Scale for Anxiety Interview Guide (HAMA-IG) and the Sheehan Patient Rated Anxiety Scale (SPRAS) were used as standards against which the HSAS was compared. RESULTS: Confirmatory factor analysis revealed a unifactorial nature for the HSAS and fewer insignificant items in the HSAS than the HAMA-IG and the SPRAS. Cronbach's alpha and test-retest coefficients indicated sufficient reliability. High correlation with the HAMA-IG and the SPRAS indicated evidence of convergence for the HSAS. ROC analysis showed high ability to distinguish between the presence and absence or remission of anxiety. Analysis of descriptive data suggested a larger dynamic range for the HSAS than the HAMA-IG and the SPRAS. CONCLUSIONS: The HSAS is a brief scale to assess anxiety severity, demonstrating evidence of good psychometric properties. It is recommended for use in research and clinical practice.