The effects of nucleus accumbens μ-opioid and adenosine 2A receptor stimulation and blockade on instrumental learning

Abstract

Prior research has shown that glutamate and dopamine receptors in the nucleus accumbens (NAcc) core are critical for the learning of an instrumental response for food reinforcement. It has also been demonstrated that μ-opioid and adenosine A2A receptors within the NAcc impact feeding and motivational processes. In these experiments, we examined the potential roles of NAcc μ-opioid and A2A receptors on instrumental learning and performance. Sprague-Dawley rats were food restricted and trained to lever press following daily intra-accumbens injections of the A2A receptor agonist CGS 21680 (at 0.0, 6.0, or 24.0 ng/side), the A2A antagonist pro-drug MSX-3 (at 0.0, 1.0, or 3.0 μg/side), the μ-opioid agonist DAMGO (at 0.0, 0.025, or 0.025 μg/side), or the opioid receptor antagonist naltrexone (at 0.0, 2.0 or 20.0 μg/side). After five days, rats continued training without drug injections until lever pressing rates stabilized, and were then tested with a final drug test to assess potential performance effects. Stimulation, but not inhibition, of NAcc adenosine A2A receptors depressed lever pressing during learning and performance tests, but did not impact lever pressing on non-drug days. Both μ-opioid receptor stimulation and blockade inhibited learning of the lever-press response, though only naltrexone treatment caused impairments in lever-pressing after the task had been learned. The effect of A2A receptor stimulation on learning and performance were consistent with known effects of adenosine on effort-related processes, whereas the pattern of lever presses, magazine approaches, and pellet consumption following opioid receptor manipulations suggested that their effects may have been driven by drug-induced shifts in the incentive value of the sugar reinforcer.

Striatopallidal adenosine A2A receptor modulation of goal-directed behavior: Homeostatic control with cognitive flexibility

“…Moreover, A 2A R in striatopallidal neural bodies of NAc and output projection terminals of ventral pallidum exert an opposite effect on Pavlovian conditioning ( Li et al, 2020 ), the former depressing and the later facilitating Pavlovian-to-instrumental transfer. Decision-making is also oppositely controlled by striatal A 2A R ( Clissold and Pratt, 2014 ; Salamone et al, 2018 ; Yu et al, 2009 ) and by prefrontocortical A 2A R ( Leffa et al, 2018 ), which exert inhibitory and facilitatory effects, respectively. Likewise, cognition is also under parallel control by striatal and hippocampal A 2A R ( Carvalho et al, 2019 ; Viana da Silva et al, 2016 ; Temido-Ferreira et al, 2020 ).…”

Anticipatory Behavior for a Mealworm Reward in Laying Hens Is Reduced by Opioid Receptor Antagonism but Not Standard Feed Intake

“…As anticipatory behavior is thought to reflect the animal's perception of a stimulus we interpret the hen's behavior to be an anticipation of the mealworm reward and conclude that control hens found the mealworms more rewarding than hens that were administered nalmefene. However, it must be noted that motivation (Le Merrer et al, 2009) or learning (Clissold and Pratt, 2014) may have also been directly impacted by nalmefene administration due to the off-target action of the drug on all opioid receptors.…”