Feeding condition and the relative contribution of different dopamine receptor subtypes to the discriminative stimulus effects of cocaine in rats

Abstract

Rationale The contribution of dopamine receptor subtypes in mediating the discriminative stimulus effects of cocaine is not fully established. Many drug discrimination studies use food to maintain responding, necessitating food restriction, which can alter drug effects. Objective This study established stimulus control with cocaine (10 mg/kg) in free-feeding and food-restricted rats responding under a schedule of stimulus shock termination (SST) and in food-restricted rats responding under a schedule of food presentation to examine whether feeding condition or the reinforcer used to maintain responding impacts the effects of cocaine. Method Dopamine receptor agonists and antagonists were examined for their ability to mimic or attenuate, respectively, the effects of cocaine. Result Apomorphine, quinpirole, and lisuride occasioned >90% responding on the cocaine-associated lever in free-feeding rats responding under a schedule of SST; apomorphine, but not quinpirole or lisuride, occasioned >90% responding on the cocaine lever in food-restricted rats responding under a schedule of SST. In food-restricted rats responding for food these drugs occasioned little cocaine lever responding and were comparatively more potent in decreasing responding. In free-feeding rats, the effects of cocaine were attenuated by the D2/D3 receptor antagonist raclopride and the D3 receptor-selective antagonist PG01037. In food-restricted rats, raclopride and the D2 receptor-selective antagonist L-741,626 attenuated the effects of cocaine. Raclopride antagonized quinpirole in all groups while PG01037 antagonized quinpirole only in free-feeding rats. Conclusion These results demonstrate significant differences in the discriminative stimulus of cocaine that are due to feeding conditions and not to the use of different reinforcers across procedures.

Effects of dopamine D2-like receptor agonists in mice trained to discriminate cocaine from saline: Influence of feeding condition

“…Similar to previous reports in food-restricted rats trained to discriminate cocaine (Baladi et al 2013; Barrett and Appel 1989; Callahan et al 1991; Filip and Przegaliñski, 1997; Terry et al 1994; but see Witkin et al 1991), both dopamine D 3 receptor-selective agonists dose-dependently increased cocaine-appropriate responding with doses of 0.32 (pramipexole) and 1.0 mg/kg (quinpirole) resulting in nearly exclusive cocaine-appropriate responding in Food- Restricted mice. Sumanirole, a dopamine D 2 receptor-selective agonist, occasioned lower levels of cocaine-appropriate responding (~40%).…”

“…Sumanirole, a dopamine D 2 receptor-selective agonist, occasioned lower levels of cocaine-appropriate responding (~40%). Unlike previous reports of apomorphine producing nearly exclusive cocaine-appropriate responding in food-restricted rats (Baladi et al 2013; Colpaert et al 1976; Witkin et al 1991), the non-selective dopamine receptor agonist only modestly increased (~60%) cocaine-appropriate responding at doses smaller than those that suppressed responding in Food-Restricted mice. Together with the results of a previous study in which a highly-selective dopamine D 3 receptor agonist, PF-592,379, failed to increase cocaineappropriate responding in food-restricted rats (Collins et al, 2012), as well as other studies in which dopamine D 3 receptor-selective antagonists failed to antagonize the cocaine-like discriminative stimulus effects of dopamine D 3 receptor-selective agonists in rats (Baker et al 1998; Baladi et al, 2013), results of the current studies provide further evidence that the discriminative stimulus effects of cocaine are mediated by both dopamine D 3 and D 2 receptors in food-restricted rodents.…”

“…Previous studies have demonstrated that feeding conditions can impact the relative contribution of receptor subtypes that mediate the discriminative stimulus effects of both direct-acting dopamine D 2 -like receptor agonists (e.g., quinpirole) and indirect-acting dopamine receptor agonists (e.g., cocaine; Baladi et al 2010; 2013). The current studies extended these general findings in several ways.…”

“…Moreover, a recent series of studies suggest that factors such as drug history, sex, and feeding condition (i.e., the amount and type of food eaten) can alter the relative contribution of particular dopamine receptor subtypes to the behavioral effects of direct- (e.g., quinpirole) and indirect-acting (e.g., cocaine) dopamine receptor agonists (Baladi and France 2010; Baladi et al 2010; 2011; 2012; 2013; Collins et al 2008). For example, the discriminative stimulus effects of quinpirole (a direct-acting dopamine D 2 -like receptor agonist) and cocaine are primarily mediated by dopamine D 2 receptors in food-restricted rats, whereas dopamine D 3 receptors play a larger role in mediating these same effects in rats that have free access to food (Baladi et al 2010; 2013).…”

“…For example, the discriminative stimulus effects of quinpirole (a direct-acting dopamine D 2 -like receptor agonist) and cocaine are primarily mediated by dopamine D 2 receptors in food-restricted rats, whereas dopamine D 3 receptors play a larger role in mediating these same effects in rats that have free access to food (Baladi et al 2010; 2013). …”