Effects of 2-AG on the reinforcing properties of wheel activity in obese and lean Zucker rats

Abstract

The endocannabinoid system plays a role in obesity, primarily by its role in food reward. Activity, also involved in obesity, seems to be at least partially controlled by the endocannabinoid system, but the relevant behavioral and neurochemical mechanisms have not been well established. This study represents an attempt to begin elucidating these mechanisms by examining the effects of an endogenous cannabinoid ligand, 2-arachidonoylglycerol (2-AG), on the reinforcing properties of exercise reinforcement in lean and obese Zucker rats. Ten obese and 10 lean Zucker rats pressed a locked door under a progressive ratio schedule of reinforcement that, when unlocked, provided access to a running wheel for 2-min periods. After baseline breakpoints were established, doses of 2-AG (0.3-3 mg/kg) were administered before experimental sessions. Obese rats exhibited lower breakpoints for wheel activity, lower response rates, and fewer revolutions compared with lean rats. 2-AG decreased breakpoints, response rates, and revolutions for obese rats, and revolutions only for lean rats. These data suggest that 2-AG may reduce the reinforcing properties of activity, and that obese Zuckers may show a greater sensitivity to 2-AG. The data also suggest that endocannabinoids may play a role in the reinforcing properties of exercise.

Respiratory muscle weakness in the Zucker diabetic fatty rat

“…Evidence of diaphragm weakness and atrophy in the absence of in vitro functional impairment. We chose to investigate the function and morphology of the diaphragm, a constitutively active muscle to remove disuse atrophy as a potential confounding variable as, while physical activity has not been specifically investigated in the ZDF strain, previous studies have identified that the obese Zucker strain has decreased spontaneous activity and wheel activity, compared with lean controls (38,39). Functional analysis of the diaphragm revealed that baseline esophageal pressures were not different between ZDF and lean controls during eupneic breathing (Fig.…”

The use of a running wheel to measure activity in rodents: Relationship to energy balance, general activity, and reward

“…Additionally, eCB regulation of exercise may be related to metabolic status as the motivation for wheel running, and the wheel-running behavior itself, is differentially responsive to cannabinoid ligands in lean compared to obese Zucker rats (Smith and Rasmussen, 2010). Taken together, the apparent role for the hippocampus in energy management, coupled with the robust effect of exercise on hippocampal structure and function, indicate that the influence of wheel running on the hippocampus should not be discounted in studies of food intake and energy expenditure.…”

Rimonabant’s reductive effects on high densities of food reinforcement, but not palatability, in lean and obese Zucker rats

“…It is possible that obese rats’ behavior was insensitive to the effects of rimonabant because of their genotype, though this is unlikely as rimonabant effects were observed in the reinforcer and response data. Moreover, a number of studies show that obese Zucker rats are especially sensitive to CB 1 compounds (Rasmussen and Huskinson 2008; Smith and Rasmussen 2010; Vickers et al 2003). It is more likely that while rimonabant reduced behavior and reinforcers earned overall across all schedules of the obese Zucker rats, the allocation of behavior did not change due to rimonabant.…”

“…After this point, access to food was restricted to a daily 2-hr free-feeding session immediately following experimental sessions; this established food as a reinforcer. This restriction procedure results in both lean and obese Zucker rats consuming 2.3–2.6% of their body weight in food (Rasmussen et al 2010; Rasmussen and Huskinson 2008; Smith and Rasmussen 2010). This also allows deprivation levels to be held constant between lean and obese rats and prevents rapid weight gain, which is linked to health problems in the obese Zucker rat.…”

“…One of the mechanisms that contributes to these differences is defective leptin signaling (Haynes et al 1997), which is also linked to higher endocannabinoid levels in the hypothalamus (Di Marzo et al 2001) and more CB 1 receptor binding sites in the limbic regions of the brain (Thanos et al 2008). These differences likely contribute to altered sensitivity to cannabinoid compounds (Smith and Rasmussen 2010), including rimonabant (Rasmussen and Huskinson 2008; Thanos et al 2008; Vickers et al 2003). We hypothesized that obese Zucker rats may be more sensitive to the effects of rimonabant, as they have been shown to be more sensitive to cannabinoid drugs.…”