Ahlers S T, Weissman B A, Barrett J E
Neurochemistry Division, Naval Medical Research Institute, Bethesda, Maryland.
J Pharmacol Exp Ther. 1992 Feb;260(2):474-81.
The purported serotonin (5-HT)1A antagonists BMY-7378 and NAN-190 were examined in pigeons for their potential to block the effects of the prototypical 5-HT1A agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) on punished ("conflict") and unpunished behavior and for their binding affinity at the 5-HT1A receptor site labeled by [3H]-8-OH-DPAT. Although BMY-7378 and NAN-190 both displayed high affinity for the 5-HT1A receptor (IC50 values of 0.8 and 7.5 nM, respectively), their effects, when administered alone, as well as in combination with 8-OH-DPAT, were distinct. 8-OH-DPAT (0.3-3.0 mg/kg) produced large increases in punished responding at doses that did not affect or that decreased unpunished responding. Administration of NAN-190 (1.0-3.0 mg/kg) did not increase punished responding, whereas BMY-7378 (1.0-5.6 mg/kg) slightly increased behavior suppressed by punishment. Pretreatment with BMY-7378 attenuated the rate-increasing effects of 8-OH-DPAT on punished responding; however, these effects were accompanied by dose-dependent enhancement of the rate-decreasing effects of 8-OH-DPAT on unpunished responding. In contrast, NAN-190 blocked the rate-increasing effects of 8-OH-DPAT on punished responding and also reversed the rate-decreasing effects of 8-OH-DPAT on responding that was not punished. Pretreatment with NAN-190 failed to block increases in punished responding produced by 0.1 to 1.0 mg/kg of the benzodiazepine midazolam. These data suggest that NAN-190 may be characterized as an antagonist and BMY-7378 a partial agonist with respect to 5-HT1A-induced behavioral changes observed in the conflict procedure with pigeons.
在鸽子身上研究了所谓的5-羟色胺（5-HT）1A拮抗剂BMY-7378和NAN-190，以考察它们阻断典型5-HT1A激动剂8-羟基-2-（二正丙基氨基）四氢萘（8-OH-DPAT）对受罚（“冲突”）行为和未受罚行为影响的潜力，以及它们对由[3H]-8-OH-DPAT标记的5-HT1A受体位点的结合亲和力。虽然BMY-7378和NAN-190对5-HT1A受体均表现出高亲和力（IC50值分别为0.8和7.5 nM），但它们单独给药以及与8-OH-DPAT联合给药时的效应却截然不同。8-OH-DPAT（0.3 - 3.0 mg/kg）在不影响或降低未受罚反应的剂量下，使受罚反应大幅增加。给予NAN-190（1.0 - 3.0 mg/kg）并未增加受罚反应，而BMY-7378（1.0 - 5.6 mg/kg）则使受惩罚抑制的行为略有增加。用BMY-7378预处理可减弱8-OH-DPAT对受罚反应的速率增加效应；然而，这些效应伴随着8-OH-DPAT对未受罚反应的速率降低效应的剂量依赖性增强。相比之下，NAN-190阻断了8-OH-DPAT对受罚反应的速率增加效应，并且还逆转了8-OH-DPAT对未受罚反应的速率降低效应。用NAN-190预处理未能阻断0.1至1.0 mg/kg苯二氮卓类咪达唑仑引起的受罚反应增加。这些数据表明，就鸽子冲突程序中观察到的5-HT1A诱导的行为变化而言，NAN-190可被表征为拮抗剂，而BMY-7378为部分激动剂。
