Tolerance to 5-HT and its implication in electro-acupuncture tolerance and morphine tolerance
Abstract
Previously we reported that electro-acupuncture tolerance (AT) or morphine tolerance (MT) were partially reversed by intra-cerebroventricular injection (icv) of 5-hydroxy tryptophan (5-HTP), the precursor of 5-HT. In this study the development of tolerance to 5-HT during AT and MT was evaluated.
Overload of 5-HT receptors was achieved by ip 5-HTP 25 mg/kg/h×6 h and the response of CNS to 5-HT was monitored by icv 5-HT 12.5 μg. The hypothermic effect of 5-HT was markedly reduced in 5-HTP loaded rats (0.6±0.8℃), in AT rats (0.8±0.5℃) and in MT rats (0.8± 0.7℃) as compared to the control rats (1.9±0.4℃, ].5±0.3℃ and 1.5±0.5℃，respectively). On the other hand, there was a reduction in the effectiveness of electro-acupuncture analgesia in 5-HTP loaded rats. The increase of tail flick latency after electro-acupuncture was only 14±41% in 5-HTP loaded rats as compared to110±29% in the control rats.
The results suggest that tolerance to endogenous 5-HT may serve as one of the possible mechanisms underlying the development of AT and MT.
Keywords:
Overload of 5-HT receptors was achieved by ip 5-HTP 25 mg/kg/h×6 h and the response of CNS to 5-HT was monitored by icv 5-HT 12.5 μg. The hypothermic effect of 5-HT was markedly reduced in 5-HTP loaded rats (0.6±0.8℃), in AT rats (0.8±0.5℃) and in MT rats (0.8± 0.7℃) as compared to the control rats (1.9±0.4℃, ].5±0.3℃ and 1.5±0.5℃，respectively). On the other hand, there was a reduction in the effectiveness of electro-acupuncture analgesia in 5-HTP loaded rats. The increase of tail flick latency after electro-acupuncture was only 14±41% in 5-HTP loaded rats as compared to110±29% in the control rats.
The results suggest that tolerance to endogenous 5-HT may serve as one of the possible mechanisms underlying the development of AT and MT.