The blockade of D1/D2-like dopamine receptors in the lateral periaqueductal gray region affects morphine self-administration with and without exercise in rats

Introduction: The periaqueductal gray (PAG) region plays an essential role in the modulation of nociception. Also, lateral PAG (lPAG) is involved in reward circuitry by the dopaminergic system in addiction. The present study investigated the blockade of D-1/D-2-like dopamine receptors in the lateral PAG region affects morphine self-administration with and without exercise. Methods: Rats were divided into six groups. The rats were initially trained to receive small pellets of food by pressing an active lever in the self administration apparatus. Exercise groups were run on a treadmill at 20m/min, 5 days/week, for 4 weeks before the surgery. Then rats were bilaterally implanted with cannulae in lPAG. The SCH23390 and sulpiride were microinjected into the lPAG, 5min before receiving morphine. Afterward, the animals were allowed to self administer morphine in 2h sessions over 11 consecutive days. At last, the numbers of lever pressing, infusion times and withdrawal symptoms were measured. Results: The results showed the number of active lever pressing was significantly increased in the morphine group compared to other groups in self-infusion during 11 days. Exercise significantly reversed the detrimental effects of morphine self-administration after five days. However, the synergistic effect of injected sulpiride into the lPAG region with exercise training was more pronounced on the amelioration of morphine than on the combinatory effect of SCH23390 with exercise. Conclusion: The findings suggested that the D-2 dopamine receptor in the lPAG region was involved in the morphine addiction via the dopaminergic system and exercise training in combination with antagonists could reduce the rewarding properties of morphine.