Cocaine Versus Food Choice Procedure in Rats: Environmental Manipulations and Effects of Amphetamine

Abstract

We have adapted a nonhuman primate model of cocaine versus food choice to the rat species. To evaluate the procedure, we tested cocaine versus food choice under a variety of environmental manipulations as well as pharmacological pretreatments. Complete cocaine-choice dose-effect curves (0–1.0 mg/kg/infusion) were obtained for each condition under concurrent fixed ratio schedules of reinforcement. Percentage of responding emitted on the cocaine-reinforced lever was not affected significantly by removal of cocaine-associated visual or auditory cues, but it was decreased after removal of response-contingent or response-independent cocaine infusions. Cocaine choice was sensitive to the magnitude and fixed ratio requirement of both the cocaine and food reinforcers. We also tested the effects of acute (0.32, 0.56, 1.0, 1.8 mg/kg) and chronic (0.1, 0.32 mg/kg/hr) d-amphetamine treatment on cocaine choice. Acute and chronic d-amphetamine had opposite effects, with acute increasing and chronic decreasing cocaine choice, similar to observations in humans and in nonhuman primates. The results suggest feasibility and utility of the choice procedure in rats and support its comparability to similar procedures used in humans and monkeys.

Choosing Under the Influence: A Drug-Specific Mechanism by Which the Setting Controls Drug Choices in Rats

“…Indeed, all else being equal, merely shortening the interchoice interval from 10 to 1 min was sufficient to make rats shift their choice from saccharin to cocaine within one single 30-trial choice session. This setting-specific control of cocaine choices in the same rats and at the same dose of cocaine (ie, 0.25 mg per injection) confirms previous research (Kerstetter et al, 2012) and helps to resolve current discrepancies across cocaine choice studies in rats, as explained in the Introduction Thomsen et al, 2013).…”

“…Remarkably, a complete and long-term suppression of methamphetamine seeking by food choice was also demonstrated in rats after different histories of extended access to methamphetamine self-administration that are known to induce addiction-like behavior (Caprioli et al, 2015a, b). In contrast, in other choice studies, rats eventually shifted their choice from sweet reward to cocaine when the dose of cocaine was sufficiently high (ie, up to 0.5 mg per injection) (Thomsen et al, 2008(Thomsen et al, , 2013.…”

“…In studies employing a setting where choosing under the drug influence was not possible (eg, by imposing a sufficiently long interchoice interval for drug dissipation before the next choice), most rats preferred sweet reward over cocaine, even at the high doses . In contrast, in studies using a setting where choosing under the drug influence was possible (eg, by not imposing a minimum interchoice interval), virtually all rats preferred the high doses of cocaine (Thomsen et al, 2008(Thomsen et al, , 2013. Thus, it seems that rats choose cocaine when they are under the drug influence at the time of choice and otherwise choose the nondrug reward.…”

“…There is growing awareness that such lack of options may limit the validity of this research for understanding drug addiction as a drug use disorder (Ahmed, 2005(Ahmed, , 2010Ahmed et al, 2013;Alexander and Hadaway, 1982;Cantin et al, 2010;Caprioli et al, 2015b;Carroll et al, 1989;Kerstetter et al, 2012;Le Sage, 2009;Lenoir et al, , 2013Liu and Grigson, 2005;Perry et al, 2013;Thomsen et al, 2013;Tunstall and Kearns, 2013;Zernig et al, 2013). Indeed, when there is no valuable alternative to the drug, drug self-administration may merely reflect a normal reaction to the lack of choice as opposed to reflecting a disordered behavior caused by an underlying dysfunction (Ahmed, 2010;Ahmed et al, 2013;Hyman and Malenka, 2001).…”

Interaction Between Behavioral and Pharmacological Treatment Strategies to Decrease Cocaine Choice in Rhesus Monkeys

“…One example of this pharmacotherapy approach is studies with the dopamine/norepinephrine-selective releaser d-amphetamine. Chronic d-amphetamine treatment produced dose-dependent and sustained decreases in cocaine self-administration under second-order, progressive-ratio, and concurrent drug vs food schedules of reinforcement in rats (Chiodo et al, 2008;Thomsen et al, 2012), nonhuman primates (Czoty et al, 2011;Negus, 2003;Negus and Mello, 2003), and/or humans (Greenwald et al, 2010;Rush et al, 2010). Overall, these studies demonstrate that cocaine self-administration in general, and cocaine vs food choice in particular, is sensitive to pharmacological manipulations.…”