8-OH-DPAT Prevents Morphine-Induced Apoptosis in Rat Dorsal Raphe Nucleus: A Possible Mechanism for Attenuating Morphine Tolerance

Kambiz Hassanzadeh
Department of Physiology and Pharmacology, Faculty of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran

Abstract:

Previously, we found that activation of serotonin 1A (5-HT1A) receptors in the dorsal raphe nucleus (DRN) decreased the development of tolerance to the analgesic effect of morphine. It has been indicated that tolerance to the analgesic effect of morphine is associated with apoptosis in the central nervous system. In this investigation the effect of 8-OH-DPAT (8-hydroxy-2-[di-n-propylamino]tetralin), a specific 5-HT1A receptor agonist, on morphine-induced tolerance and apoptosis in rat DRN was evaluated. Nociception was assessed using a hotplate apparatus. The terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) method was used to analyze apoptosis. Tolerance to the analgesic effect of morphine was complete by 10 days after morphine administration (5 mg/kg/d, i.p.), whereas a significant analgesic effect was observed through the 10th day in 8-OH-DPAT–treated animals. Furthermore, the results indicated that 8-OH-DPAT (2, 4 and 8 µg/rat/day) attenuated the number of apoptotic cells in the DRN in comparison with the control group. However, 8-OH-DPAT (8 µg/rat/d, intra-DRN) failed to reduce morphine-induced apoptosis in the presence of the 5-HT1A receptor antagonist, NAN-190 (6 µg/rat/d, intra-DRN). In conclusion we found that intra-DRN injection of a specific 5-HT1A receptor agonist attenuated morphine-induced apoptosis in rat DRN, which may have a key role in morphine tolerance.