Comparison of cocaine reinforcement in lean and obese Zucker rats: Relative potency and reinstatement of extinguished operant responding

Abstract

Aims: Evidence indicates that obese individuals exhibit alterations in brain-reward function that are anatomically and functionally similar to what has been observed in drug addicts, which could theoretically make obese individuals vulnerable to drug abuse and drug abusers vulnerable to overeating. However, few studies have investigated the cross-generality of these phenotypes. We recently reported that the reinforcing effectiveness (i.e., value) of a fat was greater in obese Zucker rats than in their lean counterparts, but found no differences in the reinforcing effectiveness of cocaine between groups, suggesting psychostimulant reinforcement is similar in lean and obese Zucker rats. However, it is unknown if other aspects of reinforcement such as cocaine's potency as a reinforcer or its reinstating effects differ in lean and obese Zucker rats.

Methods: The current study compared cocaine's potency as a reinforcer in lean and obese Zucker rats self-administering intravenous cocaine (0.06-1.0mg/kg/inj), and subsequently tested these subjects in cue- (light) and drug-primed (intraperitoneal cocaine; 10mg/kg) reinstatement of extinguished operant responding.

Results: All rats acquired cocaine self-administration and generated "inverted-U" dose-response functions. Following extinction of responding, the cue- and drug-primes increased lever-pressing in both groups (i.e., reinstatement). No significant differences in the reinforcing potency or reinstating effects of cocaine were observed as a function of obesity.

Conclusions: These results, combined with our previous observations, demonstrate that cocaine's reinforcing effects are comparable in lean and obese Zucker rats and do not support the hypothesis that obesity is associated with an altered reinforcing effect of psychostimulants.

Keywords: Cocaine; Obesity; Self-administration; Zucker rat.

Figure 1

Survival plot representation of acquisition of stable cocaine self-administration in lean (open symbols) and obese (closed symbols) Zucker rats.

Figure 2

Sensitivity to the reinforcing effects of cocaine in lean (open symbols) and obese (closed symbols) Zucker rats. (Upper panel) Mean number of cocaine injections earned per session in lean (open symbols) and obese (closed symbols) Zucker rats. (Lower panel) Mean number of cocaine milligrams earned per session in lean (open symbols) and obese (closed symbols) Zucker rats. Numbers in parentheses indicate the number of subjects that experienced a particular dose not experienced by all subjects. Error bars represent one standard error of the mean (SEM).

Figure 3

Extinction of previously reinforced operant responding plotted as the mean number of active lever-presses as a function of session in lean (open symbols) and obese (closed symbols) Zucker rats. Error bars represent one standard error of the mean (SEM).

Figure 4

Reinstatement of extinguished operant responding following reintroduction of either a drug-paired stimulus light or cocaine (lean: n 6, obese: n = 7). (Left) Number of active lever-presses under extinction (lean: diagonal bar; obese: hatched bar) and cue-induced reinstatement (lean: open bar, obese: closed bar) conditions. (Right) Number of active lever-presses under extinction (lean: diagonal bar, obese: hatched bar) and cocaine-primed reinstatement (lean: open bar, obese: closed bar) conditions. Error bars represent one standard error of the mean (SEM), and asterisks indicate a significant difference between extinction and reinstatement within a condition, p < 0.05.