TY - JOUR
T1 - Modulations of spinal serotonin activity affect the development of morphine tolerance
AU - Li, Jihn Yih
AU - Wong, Chung Hang
AU - Huang, Eagle Y.K.
AU - Lin, Yen Chien
AU - Chen, Yun Long
AU - Tan, Peter P.C.
AU - Chen, Jin Chung
PY - 2001
Y1 - 2001
N2 - To test whether modulations of spinal serotonin (5-HT) levels would affect the development of morphine tolerance, we treated rats with either intrathecal 5-HT or 5,7-dihydroxytryptamine (5,7-DHT; a 5-HT neurotoxin) in addition to systemic infusion with morphine (2 mg·kg-1·h-1). Continuous infusion of 5-HT (10 μg·6 μL-1·h-1) into the lumbar subarachnoid space of rats for 9 h accelerated the development of morphine tolerance. The area under the curve for the tail-flick latency test was 454.1 ± 35.1 in the Sham Control group vs 327.6 ± 41.0 in the 5-HT-Infused group. μ-opioid receptor binding in the lumbar spinal cord showed a decrease in the Bmax (maximal binding -46.5%), but not the binding affinity (Kd), in 5-HT-infused rats. However, intrathecal injection of 5,7-DHT (50 μg), which resulted in a 48% reduction in 5-HT and 51% reduction in 5-hydroxyindoleacetic acid concentrations, led to an attenuation of morphine tolerance (the area under the curve was 613.0 ± 24.7 in the 5,7-DHT-Lesioned group). The binding study indicated that the affinity of lumbar μ-opioid receptors decreased 196% in 5-HT-depleted rats, whereas there was no effect on apparent binding. The infusion of 5-HT (10 μg·6 μL-1·h-1) was not analgesic and the 5,7-DHT-induced lesion did not affect acute morphine-induced analgesia. We conclude that activity of spinal 5-HT-containing neurons plays a crucial role during the development of morphine tolerance.
AB - To test whether modulations of spinal serotonin (5-HT) levels would affect the development of morphine tolerance, we treated rats with either intrathecal 5-HT or 5,7-dihydroxytryptamine (5,7-DHT; a 5-HT neurotoxin) in addition to systemic infusion with morphine (2 mg·kg-1·h-1). Continuous infusion of 5-HT (10 μg·6 μL-1·h-1) into the lumbar subarachnoid space of rats for 9 h accelerated the development of morphine tolerance. The area under the curve for the tail-flick latency test was 454.1 ± 35.1 in the Sham Control group vs 327.6 ± 41.0 in the 5-HT-Infused group. μ-opioid receptor binding in the lumbar spinal cord showed a decrease in the Bmax (maximal binding -46.5%), but not the binding affinity (Kd), in 5-HT-infused rats. However, intrathecal injection of 5,7-DHT (50 μg), which resulted in a 48% reduction in 5-HT and 51% reduction in 5-hydroxyindoleacetic acid concentrations, led to an attenuation of morphine tolerance (the area under the curve was 613.0 ± 24.7 in the 5,7-DHT-Lesioned group). The binding study indicated that the affinity of lumbar μ-opioid receptors decreased 196% in 5-HT-depleted rats, whereas there was no effect on apparent binding. The infusion of 5-HT (10 μg·6 μL-1·h-1) was not analgesic and the 5,7-DHT-induced lesion did not affect acute morphine-induced analgesia. We conclude that activity of spinal 5-HT-containing neurons plays a crucial role during the development of morphine tolerance.
UR - https://www.scopus.com/pages/publications/0035024477
U2 - 10.1097/00000539-200106000-00043
DO - 10.1097/00000539-200106000-00043
M3 - 文章
C2 - 11375847
AN - SCOPUS:0035024477
SN - 0003-2999
VL - 92
SP - 1563
EP - 1568
JO - Anesthesia and Analgesia
JF - Anesthesia and Analgesia
IS - 6
ER -