Establishment of a chronic activity-based anorexia rat model

Abstract

The optimal parameters to achieve complete amenorrhoea included early adolescence, chronic starvation and 25% weight loss. The new ABA model allows studying the effects of chronic AN on underlying behavioural, hormonal and brain pathobiology.

Activity Based Anorexia as an Animal Model for Anorexia Nervosa–A Systematic Review

“…Chronic ABA also reduced the volumes of the cerebral cortex and corpus callosum, Glial fibrillary acidic protein positive astrocytes in these regions, total astrocyte-covered area and astrocyte mRNA expression (196), alterations that likely contribute to the neuropsychological deficits observed in AN. Lastly, comparing different ages, 4-week old rats displayed increased hyperactivity and amenorrhea compared to 8-week old animals (123), indicating that younger animals are more vulnerable to chronic ABA.…”

“…Since females take longer to reach the weight loss criterion (44), in order to mimic and better understand human AN, female animals should be examined in a more long term protocol. Comparing different ages, younger rats develop ABA more rapidly (123). To develop ABA in an adult rodent population takes substantially longer than in adolescence, probably resulting from the fact that—besides absence of significant body weight gain during this period—escalation of running is often blunted in adults compared to adolescent rats.…”

“…Female adolescent rats that lost 20% of body weight due to ABA and subsequently exposed to an additional 2-week weight holding phase displayed a significantly disrupted menstrual cycle and E2 reduction compared to rats whose menstrual cycle was assessed just after the 20% body weight loss (195). Similarly, chronic starvation by food restriction to 40% of the baseline food intake and 24 h/day running wheel access until a 20–25% weight reduction followed by weight holding due to individual food restriction, resulted in a loss of the estrous cycle in all animals with 25% body weight loss, while acute ABA disrupted estrous cycle only in 58% of rats (123). In addition, due to the chronic ABA protocol in female rats an impaired memory function was observed with a correlation between E2 reduction and memory loss (195), possibly giving rise to E2 substitution as therapeutic attempt to treat cognitive deficits in AN.…”

Epigenetic regulation of the cannabinoid receptor CB1 in an activity‐based rat model of anorexia nervosa

“…Moreover, only the use of a long‐term protocol would be also useful in order to establish bone metabolism parameters similar to those observed in AN patients (Mequinion et al, 2015). It has been also observed that younger rats might be more vulnerable to chronic ABA since these animals showed higher hyperactivity and amenorrhea (Frintrop et al, 2018). Future studies are thus needed to also evaluate the epigenetic regulation of Cnr1 as well as other target genes in an ABA chronic model also in order to understand how these environmental cues affect genes regulation over the time.…”

“…First of all, AN is a disease enduring over several years and has a high relapse rate and we here used a short‐term ABA protocol. Recently, new chronic ABA models showed that in these rats' menstrual cycle was disrupted and E2 reduced when compared to acute ABA (Frintrop et al, 2018; Paulukat et al, 2016). Moreover, only the use of a long‐term protocol would be also useful in order to establish bone metabolism parameters similar to those observed in AN patients (Mequinion et al, 2015).…”