Cannabinoid CB₁/CB₂ receptor agonists attenuate hyperactivity and body weight loss in a rat model of activity‐based anorexia

Abstract

Taken together, our results further demonstrate the involvement of the EC system in AN pathophysiology and that strategies which modulate EC signalling are useful to treat this disorder, specifically in patients where physical hyperactivity plays a central role in its progression and maintenance.

Impaired brain endocannabinoid tone in the activity‐based model of anorexia nervosa

“…Results of the recovery phase replicated our previously published data (Scherma et al, ). Specifically, ABA rats recovered to baseline body weight within the first 4 days of the recovery phase; however, at the end of this phase, their weight was significantly less than that of Control rats (Day 7: body weight Recovered ABA −6% vs. Control) [Two‐way ANOVA group × time interaction: F (7, 112) = 15.07, p < .0001; Figure ].…”

“…For example, decreased 2‐AG levels and reduced CB1R expression in the Hipp of rats were found after chronic exposure to stress, suggesting that glucocorticoids exert a negative regulation over CB1R transcription (Hill et al, ). Consistent with this, we have recently shown increased corticosterone levels in the plasma of our individually housed ABA rats (Scherma et al, ). However, it is important to consider that a human PET study in vivo found that CB1R availability was globally increased in patients with AN compared with healthy control subjects (Gérard et al, ).…”

“…The behavioral patterns of food intake, body weight, and physical activity exhibited by ABA rats during the ABA induction and recovery phases, resembles our previously published data (Scherma et al, ).…”

“…As previously demonstrated (Scherma et al, ; Verty et al, ), rats (ABA group) placed on a restricted‐feeding schedule (1.5‐hr/day access to food) and provided access to a running wheel exhibited a progressive and significant body weight loss to a total of −23% of the initial body weight (baseline) (Two‐way ANOVA group × time interaction: F (6, 204) = 182.2, p < .0001; Figure ). Control rats that had ad libitum access to food and no access to the running wheel showed a progressively age‐related increase in their body weight.…”

“…In fact, exposure to the natural CB1R/CB2R agonist Δ 9 ‐tetrahydrocannabinol (THC) was able to attenuate the progressive body weight loss associated with the development of the ABA condition (Verty et al, ). In agreement, we have recently demonstrated the effectiveness of THC as well as that of the synthetic CB1R/CB2R agonist CP‐55,940 in reducing both body weight loss and hyperactivity in rats subjected to a repeated ABA regimen (Scherma et al, ).…”