Systemic administration of the adenosine A2A agonist CGS 21680 induces sedation at doses that suppress lever pressing and food intake

Abstract

Adenosine A 2A receptors are involved in the regulation of several behavioral functions. Adenosine A 2A antagonists exert antiparkinsonian effects in animal models, and adenosine A 2A agonists suppress locomotion and impair various aspects of motor control. The present experiments were conducted to study the effects of low doses of the adenosine A 2A agonist CGS 21680 on lever pressing, specific parameters of food intake, and sedation. In the first experiment, the effects of CGS 21680 on fixed ratio 5 lever pressing were assessed. In the second experiment, rats were tested in 30 min feeding sessions, and also were observed for drug-induced sedation using a sedation rating scale. CGS 21680 (0.025, 0.05, 0.1 mg/kg IP) produced a dose related suppression of lever pressing, and also reduced the amount of food consumed. The feeding effect was largely dependent upon a slowing of the rate of feeding, and there was only a modest suppression of time spent feeding. Doses of CGS 21680 that suppressed lever pressing and feeding also were associated with sedation/drowsiness. In conjunction with other studies, the present results suggest that sedative effects may play an important role in some of the behavioral effects produced by systemic administration of adenosine A 2A agonists.

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).…”

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

“…This study employed a sedation rating scale adapted from Salamone et al (1996) and Chuck et al (2006), and showed that, in the same systemic dose range that also suppressed FR5 lever pressing and feeding, CGS 21680 (0.05 and 0.1 mg/kg IP) significantly induced overt signs of sedation/drowsiness that included foot dragging, stumbling, ataxia, flattened posture, lowered head, and partially closed eyes. In the Mingote et al (2008) study, 0.1 mg/kg CGS 21680 produced a level of sedation that was comparable to that induced by 2.0 g/kg ethanol (Chuck et al 2006), which is a dose of ethanol that also suppressed lever pressing. Thus, the absence of a shift from lever pressing to chow intake following systemic administration of CGS 21680 is likely to be due to a sedation/ drowsiness effect.…”

Effort-related motivational effects of the pro-inflammatory cytokine interleukin 1-beta: studies with the concurrent fixed ratio 5/ chow feeding choice task

“…Also, drugs that produce substantial drowsiness/sedation (e.g. the adenosine A 2A agonist CGS 21680) have been shown to decrease both lever pressing and chow intake (Mingote et al 2008b), and did not induce the shift from lever pressing to chow intake at systemic doses that induced sedation (Font et al 2008). Our own pilot studies indicated that higher doses of IL-1β could suppress food intake in addition to lever pressing, but the low doses used in experiments 1 above enabled us to observe a shift if choice from lever pressing to chow intake.…”