Interaction of opioid and D2-like dopamine receptors in the nucleus accumbens modulate acute pain-related behaviors

Abstract

As a pivotal component of the reward circuitry in the brain, the nucleus accumbens (NAc) is essential in influencing pain-related reactions. Its involvement suggests a significant interplay with the systems that utilize opioids and dopamine. This research investigated the interplay between opioidergic and D2-like dopamine receptors within the NAc on acute pain-related behaviors. Male Wistar rats underwent unilateral cannula implantation into the NAc. In the initial phase, separate groups of animals were administered varying doses of morphine (5, 10, and 25 mmol/0.5 μL) and quinpirole (2, 4, 8, and 16 mmol/0.5 μL), acting as an opioid and a D2-like receptor agonist in the NAc, respectively. Following this, the animals received different doses of sulpiride (1.5, 3, 6, 12, and 24 mmol/0.5 μl), a D2-like receptor antagonist, prior to receiving an effective dose of morphine (10 mmol/0.5 μL). In the final phase, animals were given varying doses of naloxone (1.5, 5, 15, and 45 mmol/0.5 μl) before administering the efficacious dose of quinpirole (8 mmol/0.5 μl). This study employed the tail-flick test, which was subsequently used to assess the subjects' acute pain threshold. The primary results indicated that the administration of morphine and quinpirole into the NAc independently produced antinociceptive effects. Conversely, injecting sulpiride into the NAc significantly reduced the pain-relieving effects of morphine in the NAc. Additionally, introducing naloxone into the NAc greatly weakened the antinociceptive consequences linked to the quinpirole administration. The findings suggest a possible interaction between the dopamine and opioid systems within the NAc that may lead to pain relief. This understanding could guide the creation of new medications designed to enhance pain management while reducing the risks linked to conventional opioid treatments.