Biology subjects

Ebenezer, I. S.

Publications and source records attributed to Ebenezer, I. S..

3 recordsLinked to original sources

bioRxiv2025

Does repeated administration of baclofen in free feeding rats reduce body weight by stimulating brown fat metabolism through activation of the sympathetic nervous system?

The results of previous research have suggested that chronic administration of the GABAB receptor agonist baclofen can lead to weight loss in rodents by potentially activating brown adipose tissue (BAT) to increase metabolism rate. Studies in anaesthetised rats have shown that baclofen injected directly into the ventromedial nucleus of the hypothalamus (VMH) stimulates BAT to increase thermogenesis. This effect was attenuated by pretreatment with the beta-adrenoceptor antagonist propranolol, suggesting that baclofen microinjected into the VMH stimulate the sympathetic outflow to BAT, consequently increasing metabolic rate. The present study was designed to test this hypothesis by investigating whether pretreatment with propranolol would attenuate the weight loss induced by repeated daily administration of baclofen in free feeding rats. In the first experiment, male Wistar rats were injected intraperitoneal (ip) once daily for 24 days with either saline followed by saline, saline followed by baclofen (4 mg / kg), propranolol (10 or 20 mg / kg) followed by saline, or propranolol (10 mg / kg) followed by baclofen (4 mg / kg), with 5 minutes separating each injection. Body weight was measured each day 24 h after drug administration. Baclofen treatment resulted in significant reductions in daily body weight compared to the saline group. Propranolol alone had no significant effect on body weight. Importantly, pretreatment with propranolol did not attenuate the weight loss induced by baclofen. A similar experimental protocol as described above was used in a second experiment except that the rats were pretreated with a 20 mg / kg dose of propranolol and body weight was measured for 6 days. The high dose of propranolol significantly decreased body weight compared with control data and potentiated the baclofen-induced reduction in body weight. These results suggest that the effects of baclofen of body weight in free feeding rats may not be dependant on the the activation of BAT through stimulation of the sympathetic nervous system (SNS). Further research is therefore necessary to understand how baclofen influences metabolism and weight loss.

pharmacology and toxicology↗

bioRxiv2025

Repeated intraperitoneal administration of the GABAB receptor agonist baclofen reduces body weight in the mouse.

Chronic intraperitoneal (ip) administration of the GABAB receptor agonist baclofen has been shown to reduce body weight in rats without significantly affecting daily food intake. The present study was undertaken to extend these observations to another rodent species. Male C57B/10 mice (n=27) that had free access to food and water were injected once daily for 15 days with either saline or baclofen (4 or 8 mg / kg; i.p). Body weight and food intake were measured 24h after each injection. Statistical analysis of the results revealed that the 4 mg / kg dose of baclofen significantly reduced body weight gain in the mice during the first 5 days while the 8 mg / kg dose reduced body weight gain throughout the 15 days of the study when compared with saline control animals (F(2,21)=4.88, P<0.02). Baclofen (4 or 8 mg / kg) generally had no significant effects on daily 24h food intake except on days 1 and 2 when the 8 mg / kg dose produced small but significant decreases in food intake (P<0.05) that were probably due to the initial depressant effects of the drug on behaviour. The results of this study extend previous findings in rat to another rodent species and show that systemic administration of the GABAB receptor agonist baclofen reduces body weight gain in the mouse without affecting daily food intake. These results lend further support to the hypothesis that GABAB receptor agonists decreases body weight by increasing metabolic rate.

pharmacology and toxicology↗

bioRxiv2023

The effects of repeated intraperitoneal administration of the GABAB receptor agonist baclofen on body weight in rats maintained on a restricted feeding schedule.

It has previously been shown that chronic systemic administration of the GABAB agonist, baclofen, reduces body weight in free feeding rats but has no effect on long-term food intake. The present study was conducted to extend these observations by investigating the effects of baclofen on body weight, food intake and water consumption in rats maintained on a restricted feeding schedule. The rats were allowed free access to food for 3 hours each day and injected intraperitoneally (i.p) once daily over a period of 11 days with baclofen (4 mg / kg; n=8) or saline (Control Group; n=8) immediately after each feeding session. Baclofen treatment produced small decreases in food intake on Days 2, 4 and 5 (P<0.05) compared with control animals but there were no differences between the 2 groups on Days 6 to 11. Baclofen did not affect prandial water intake. However, baclofen significantly decreased body weight gain of the animals (F(1,14) = 22.0, P < 0.01) starting 3 days after the initiation of treatment. During the subsequent 9 days both groups received no treatments. However, the "Baclofen Group" continued displaying significant reductions in body weight gain (F(1,14) = 8.47 p<0.01) but there were no significant differences in food and water consumption between the 2 groups of animals. The results of this study indicate that repeated administration of baclofen to food-restricted rats for 11 days reduces body weight and that the effects persist when the drug is withdrawn. While it is possible that the decrease in food intake during the early period of the experiment may have been partly responsible for the reduction in body weight in the baclofen-treated animals, the observation that these rats displayed reduction in body weight during the latter part of the study when there was no significant differences in food intake between the 2 groups, suggests that the drug decreases body weight independently of its effects on food consumption.

pharmacology and toxicology↗