Intra-accumbens injections of the adenosine A2A agonist CGS 21680 affect effort-related choice behavior in rats

Abstract

Rationale-Nucleus accumbens dopamine (DA) participates in the modulation of instrumental behavior, including aspects of behavioral activation and effort-related choice behavior. Rats with impaired accumbens DA transmission reallocate their behavior away from food-reinforced activities that have high response requirements and instead select less-effortful types of food-seeking behavior. Although accumbens DA is considered a critical component of the brain circuitry regulating effortrelated processes, emerging evidence also implicates adenosine A 2A receptors.Objective-The present work was undertaken to test the hypothesis that accumbens A 2A receptor stimulation would produce effects similar to those produced by DA depletion or antagonism.Materials and methods-Three experiments assessed the effects of the adenosine A 2A agonist CGS 21680 on performance of a concurrent choice task (lever pressing for preferred food vs. intake of less preferred chow) that is known to be sensitive to DA antagonists and accumbens DA depletions.Results-Systemic injections of CGS 21680 reduced lever pressing but did not increase feeding. In contrast, bilateral infusions of the adenosine A 2A receptor agonist CGS 21680 (6.0-24.0 ng) into the nucleus accumbens decreased lever pressing for the preferred food but substantially increased consumption of the less preferred chow. Injections of CGS 21680 into a control site dorsal to the accumbens were ineffective.Conclusions-Taken together, these results are consistent with the hypothesis that local stimulation of adenosine A 2A receptors in nucleus accumbens produces behavioral effects similar to those induced by accumbens DA depletions. Accumbens adenosine A 2A receptors appear to be a component of the brain circuitry regulating effort-related choice behavior.

On the role of adenosine (A)2A receptors in cocaine-induced reward: a pharmacological and neurochemical analysis in rats

“…Inhibitory effects of CGS 21680 on both FR and PR schedules of cocaine self-administration clearly indicate an action on motivational properties of cocaine which is in line with other behavioral reports in rats showing an effective reduction of cocaine addictive responses following A 2A receptor agonism or in rats overexpressing neuronal A 2A receptors (for review see Filip et al 2012). Similarly in a food self-administration paradigm, CGS 21680 dose dependently blocked operant responding for food, and this finding extends previous studies in which the A 2A receptor agonist, following systemic or accumbal injections, reduced effort-related food choice behavior (Font et al 2008;Mingote et al 2008) or bingerelated eating disorders (Micioni di Bonaventura et al 2012).…”

“…These interesting and unexpected results in cocaine self-administered animals, being reversed by the systemic pretreatment with the selective A 2A receptor antagonist KW 6002, may be explained by the A 2A receptor agonist induced enhancement of either the rewarding properties of cocaine or the need for more cocaine to obtain the rewarding action. The latter alternative seems the probable one since the A 2A receptor agonist: (1) reduces the descending limb of the dose-response curve in cocaine selfadministration, (2) mimics the actions of DA D 1 or D 2 -like receptor antagonists which given before cocaine in selfadministration studies increase the animals' responding on a FR schedule of reinforcement (e.g., Phillips et al 1994;Caine et al 2002;Barrett et al 2004) and enhances an initial burst responding and increases cocaine inter-infusion intervals across the 2-h session (the present study), (3) avoids actions on brain areas related to sedation (Font et al 2008), and (4) produces a clear-cut decrease in the cocaine-induced increases in extracellular accumbens DA levels which is regarded to be one of the main mechanisms in the rewarding and motor stimulating effects of psychostimulants.…”

Role of dopamine–adenosine interactions in the brain circuitry regulating effort-related decision making: insights into pathological aspects of motivation

“…In rats responding to the operant FR5/chow feeding concurrent choice procedure, injections of CGS 21680 into the accumbens core decreased lever pressing and increased chow intake [120], a pattern of effects similar to that produced by accumbens DA depletions and antagonism. Injections of CGS 21680 into a control site dorsal to nucleus accumbens were ineffective [120].…”

“…Investigators have also studied adenosine A 2A receptor pharmacology in relation to cognitive processes [117] and anxiety [118]. Within the last few years, the motivational significance of adenosine A 2A receptor pharmacology has become apparent, especially with regard to aspects of behavioral activation and effort-related processes [84,[119][120][121].…”

“…More recently, it was demonstrated that local injection of CGS 21680 into nucleus accumbens core reduced response on a VI 60 s schedule with an attached FR10 requirement attached, but did not impair performance on a standard VI 60 s schedule [121], an effect that has been shown to occur following accumbens DA depletions [68]. In rats responding to the operant FR5/chow feeding concurrent choice procedure, injections of CGS 21680 into the accumbens core decreased lever pressing and increased chow intake [120], a pattern of effects similar to that produced by accumbens DA depletions and antagonism. Injections of CGS 21680 into a control site dorsal to nucleus accumbens were ineffective [120].…”