Depression and anxiety behaviour in a rat model of chronic migraine

Abstract

Background: Epidemiological and clinical studies have demonstrated comorbidity between migraine and affective disorders. However, it is unclear whether chronic migraine can lead to affective disorders in other animals.

Methods: A classical chronic migraine rat model (repeated dura mater inflammatory soup [IS] infusion) was used to evaluate depression and anxiety behaviour via weight, sucrose preference test, open field test and elevated plus maze test.

Results: We found that sucrose preference, locomotor and rearing behaviours, inner zoon distance percent, open-arm entries percent and serotonin and dopamine levels in the prefrontal cortex decreased significantly in the IS group compared with those in the control group; co-administration of low-dose amitriptyline ameliorated these deficits. However, no differences in weight, inner zone time percent, or open-arm time percent between the IS and control groups. These results were used to create new depression and anxiety scales to comprehensively assess and evaluate the degree of affective disorders in rats. Most of chronic migraine animals showed depression and anxiety like behaviors but a few didn't.

Conclusions: Most of the chronic migraine rats were present depression and anxiety like behaviors. The new scales we created are expected to use in the future studies to find out the potential mechanism of affective disorders' comorbidity.

Keywords: Anxiety; Chronic migraine; Depression; Scale.

Fig. 1

Behavioural studies of allodynia, depression, and anxiety. a: Facial withdraw threshold. b–e: Depressive behaviours. f–g: Anxiety behaviours. a–c: The horizontal axis shows time, and the vertical axis shows the values. The facial withdraw threshold (a) decreased gradually in the inflammatory soup (IS) and IS + amitriptyline (AMI) groups, and was significantly different form the control (CON) group on Day 3 (***P < 0.001, IS and IS + AMI group vs. CON group). However, the threshold increased gradually in the IS + AMI group on Day 8 and was significantly different from the IS group (#P < 0.05, vs. IS group). No difference in weight was detected among the four groups (b, d) (P > 0.05). Sucrose preference (c, e) was significantly lower in the IS group than that in the CON group after 21 d of administration (*P < 0.05, IS vs. CON); no difference was found between the IS and IS + AMI groups. Travel distances (f), number of explorations (g), and inner zone distance percent (ID%) (h) on the open field (OF) test were all significantly lower in the IS group than those in the CON group but recovered after AMI treatment (*P < 0.05 and ***P < 0.001, IS vs. CON; #P < 0.05 and ##P < 0.01, IS vs. IS + AMI). Inner zone time percentage (i) tended to be lower in the IS group. Open-arm time percentage (OT%) (j) and entry percentage (OE%) (k) on the elevated plus maze test were lower in the IS group than those in the CON group; only OE% was significantly different (*P < 0.05, IS vs. CON; #P < 0.05, IS vs. IS + AMI)

Fig. 2

Depression and anxiety scale scores. a–d: Depression-associated scores. e–h: Anxiety-associated scores. Facial withdraw threshold. b–e: Depressive behaviours. i: All depression scores together. j: All anxiety scores together. k: Relationship between total anxiety and total depression scores. The results were similar to the primary behavioural data, except for the inner zone time percentage (IT%) (f), which was significantly different, and open-arm entries (OE%) (h), in which the significant difference disappeared. Total depression (i) and anxiety scores (j) were significantly lower in the IS group (*P < 0.05, ***P < 0.001, IS vs. CON) but improved in the IS + AMI group (##P < 0.01, IS vs. IS + AMI). More depression paralleled more anxiety in most of the rats (k). However, a few rats had only anxiety or only depression

Fig 3

Concentrations of serotonin (a) and dopamine (b) in the prefrontal cortex measured by ELISA. 5-HT and dopamine concentrations were significantly lower in the IS group than those in the CON and IS + AMI groups in the prefrontal cortex. No differences were found between the CON and AMI groups (***P < 0.001, IS vs. CON; ###P < 0.001, groups IS vs. IS + AMI.)