Rényi L, Möller K A, Ensler K, Evenden J
Department of Behavioural Pharmacology, Astra Arcus AB, Södertälje, Sweden.
Neuropharmacology. 1992 Dec;31(12):1265-8. doi: 10.1016/0028-3908(92)90055-t.
The effects of acute doses of 8-hydroxy 2-(di-n-dipropylamino)tetralin (8-OH-DPAT) on the hypothermic response, induced by a challenge dose of 8-OH-DPAT, were examined in rats. Acute doses of 8-OH-DPAT (1.0 or 0.5 mg/kg, s.c.) significantly attenuated the hypothermic response induced by 8-OH-DPAT (0.05 mg/kg, s.c.). The response to 8-OH-DPAT was almost abolished between 4 hr and 4 days and the attenuation of the response lasted for 21 days. On day 28 the response had returned to the control level. The non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist, (+)-5-methyl-10,11-dihydro-5H-dibenzo-(a,d)cyclohepten-5,10-imine [(+)MK-801], blocked this long-lasting attenuation of the 8-OH-DPAT-induced hypothermic response. Given on its own, (+)MK-801 did not reduce body temperature, at the doses used in the experiments but the drug did block the acute effects of 8-OH-DPAT, at the same doses which blocked the attenuation of the hypothermic response. The present data suggest that stimulation of glutamate NMDA receptors may underlie the long-lasting effect of acute injections of 8-OH-DPAT.
研究了急性剂量的8-羟基-2-（二正丙基氨基）四氢萘（8-OH-DPAT）对大鼠因给予激发剂量的8-OH-DPAT所诱导的体温过低反应的影响。急性剂量的8-OH-DPAT（1.0或0.5毫克/千克，皮下注射）显著减弱了由8-OH-DPAT（0.05毫克/千克，皮下注射）诱导的体温过低反应。对8-OH-DPAT的反应在4小时至4天之间几乎消失，且反应的减弱持续了21天。在第28天，反应恢复到了对照水平。非竞争性N-甲基-D-天冬氨酸（NMDA）受体拮抗剂（+）-5-甲基-10,11-二氢-5H-二苯并（a,d）环庚烯-5,10-亚胺[（+）MK-801]阻断了8-OH-DPAT诱导的体温过低反应的这种长期减弱。单独给予时，在实验所用剂量下（+）MK-801不会降低体温，但该药物在阻断体温过低反应减弱的相同剂量下确实阻断了8-OH-DPAT的急性效应。目前的数据表明，谷氨酸NMDA受体的刺激可能是急性注射8-OH-DPAT产生长期效应的基础。
