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Cannabidiol (CBD) is a major non-psychotropic compound derived from Cannabis that has wide therapeutic potential. In our previous studies we observed decreased body weight gain in rapidly growing rats (10 weeks of age at the start of study) treated with CBD for 14 consecutive days. The present study aimed to evaluate the effects of repeated CBD administration on body weight gain, food intake and accumulation of abdominal adipose tissue in rats fed standard (SD) and high fat (HFD) diet. Adult male Wistar rats (n = 36) weighing approximately 400 g at the beginning of the experiment (14 weeks of age), fed with SD only, or having access to free choice HFD (60% kcal from fat, 10% kcal from sucrose) received intraperitoneal injections of CBD or vehicle for 14 consecutive days (5 mg/kg/day). Body weight gain as well as food and water intake were measured daily. Total amount of intra-abdominal adipose tissue was assessed by a dissection method. In contrast to previous observations in younger rats, repeated CBD administration induced significant increase in body weight gain of rats fed SD, but no significant change in food or water intake was observed. CBD produced tendency for decreased body weight gain in rats fed with HFD, but it did not reach level of significance. CBD did not affect total energy intake in rats that had access to HFD, but slightly increased preference for SD. CBD administration reduced intra-abdominal adipose tissue accumulation in rats with access to HFD, but not in rats fed with SD only. The results suggest that CBD may produce different effects on body weight gain depending on age or the metabolic state of the animal. Moreover, the results indicate that CBD may decrease accumulation of intra-abdominal adipose tissue in animals under HFD.
Cannabidiol (CBD) is a major non-psychotropic compound of cannabis that has been reported to exert neuroprotective, antipsychotic and anxiolytic effects. CBD has promising anti-inflammatory properities, but despite therapeutic potential its mechanisms of action remain poorly understood. Our previous study revealed decrease in number of lymphocytes B and T in peripheral blood following repeated CBD administration. The present study aimed to assess effects of repeated administration of CBD on distribution of lymphocyte subsets in the spleen and the involvement of CB2 receptors. Adult male Wistar rats (n=35, 10 weeks of age at the start of study) received intraperitoneal injections of CBD at a dose of 5 mg/kg/day, or the vehicle, for 14 consecutive days. Total and relative numbers of lymphocyte T (T CD4+, and T CD8+), B, NK subsets were determined by flow cytometry. The selective CB2 receptor antagonist AM630 (1 mg/kg) was administered 15 min before CBD (or the vehicle) in order to block CB2 receptors. Repeated administration of CBD decreased total leukocyte number resulting from decreased numbers of lymphocytes B and T (both T CD8+ and T CD4+) in the spleen. Pretreatment with CB2 receptor antagonist partially inhibited CBD-induced decrease in lymphocyte number that was most pronounced in case of T CD8+ lymphocytes. AM630 itself produced slight decline in lymphocyte number that did not reach statistical significance. Observed effects were accompanied by a decrease in body weight gain, which was prevented by pretreatment with CB2 antagonist. The results indicate that CBD reduces lymphocyte number in the spleen, as it does in peripheral blood and that CBD has ability to affect the lymphocyte number via CB2 receptor.
Cannabidiol (CBD) is a major non-psychotropic constituent of Cannabis. The endocannabinoid system, which can be modulated by administration of CBD, is known to play an important role in control of food intake and energy balance. In recent years, numerous studies have revealed various pharmacological effects of CBD such as neuroprotective, analgetic, anxiolytic, antipsychotic and anti-inflammatory properties, and also antitumor potential. Surprisingly, very few reports concern effects of CBD on feeding behavior. Our previous studies revealed decreased body weight gain following repeated CBD administration in rats. The present study aimed to assess acute food intake in deprived rats under standard (SD) and high fat diet (HFD). Adult male Wistar rats (n=40), weighing approximately 350 ± 30 g were food deprived for 24 h and 30 minutes before return of food rats received intraperitoneal injections of CBD (5 mg/kg) or the vehicle. Rats were fed with SD (12% kcal from fat) only, or had additional access to HFD (60% kcal from fat, 10% kcal from sucrose). Food and water intake was measured 1 h, 2 h, 3 h and 24 h after animals were allowed ad libitum access to their assigned diet. Administration of CBD induced significant decrease in food intake of deprived rats within first 3 hours after food was returned in rats fed with SD only. Total energy intake within 24 h was not significantly altered in rats fed with SD. No change in total energy intake or preference of SD and HFD was observed in rats that had access to free choice HFD. CBD did not affect water intake or defecation. The results indicate that acute dose of CBD may decrease food intake in food deprived animals fed with SD, but not in rats having access to HFD. The data indicate that effects of acute CBD administration in deprived rats depend on type of diet.
The expression of dopamine, dopamine receptors and dopamine active transporters in peripheral lymphoid tissues and lymphocytes suggest that increased dopaminergic activity induced by cocaine may be involved in regulation of the distribution of lymphocyte subsets in the spleen. Adult male Wistar rats implanted with jugular vein catheter received cocaine hydrochloride (3 × 5 mg/kg/ml, i.v., at 30 min intervals) or saline infusions. Animals were pretreated with haloperidol (1 mg/kg/ml, i.v.) or vehicle 10 min prior to the first cocaine infusion. After each cocaine infusion the locomotor-activating effects of cocaine were measured. The spleens were collected 30 min after the third cocaine infusion and total splenocyte numbers and percentage numbers of leukocyte subpopulations were assessed using a morphological method. Three-color immunofluorescent antibody staining procedure (CD3-FITC/CD45RA-PC7/CD161A-APC and CD3-FITC/ CD4-PC7/CD8-APC) was used for determination of T, B, NK, T CD4+ and T CD8+ lymphocyte subsets. Plasma corticosterone and serum concentrations of IL-4, IFN-gamma and cocaine were assessed. In the spleen, administration of cocaine after pretreatment with haloperidol decreased numbers of splenocytes, lymphocytes and T CD4+ and B lymphocytes, significantly in comparison to rats treated with cocaine alone. The proportions between lymphocyte subsets and CD4/CD8 ratio in the spleen were not affected. Cocaine or/and haloperidol increased plasma corticosterone concentration. Serum cocaine concentration indicated the possibility of accumulation of cocaine in the applied schedule of administration. Serum concentrations of IL-4 and IFN-gamma were not altered. Haloperidol abolished locomotor response induced by cocaine infusions. In conclusion, dopaminergic activity following administration of cocaine is involved in retention of T CD4+ and B lymphocytes in the spleen of rats.
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