Differential effects of 5-hydroxytryptamine1a selective drugs on the 5-HT behavioral syndrome.

Four drugs that bind to the same serotonin receptor subtype (5-HT1A) produce different behavioral effects in rats. 8-OH-DPAT, 5-MeODMT, buspirone, and isapirone all potently inhibit 3H-8-OH-DPAT binding to rat brain membranes (Ki values = 1.9-13 nM). However, only 8-OH-DPAT and 5-MeODMT induce forepaw treading, head-weaving, and tremor, while buspirone and isapirone actually block those behaviors when given alongside the full agonists. All four drugs induce hindlimb abduction, flattened body posture, and Straub tail. The findings suggest that specific components of the serotonin behavioral syndrome are mediated by 5-HT1A receptors.

Study at a glance

Abstract

The effects of 8-hydroxy-2-(di-n-propyl-amino) tetralin (8-OH-DPAT), 5-methoxy-N,N-dimethyltryptamine (5-MeODMT), buspirone and isapirone were examined at 5-hydroxytryptamine1A (5-HT1A) binding sites and on the 5-HT behavioral syndrome in the rat. 8-OH-DPAT, 5-MeODMT, buspirone and isapirone are all potent inhibitors of 3H-8-OH-DPAT binding to rat brain membranes (Ki values = 1.9-13 nM). However, these drugs have differential effects on the 5-HT behavioral syndrome. 8-OH-DPAT, 5-MeODMT and buspirone induce hindlimb abduction, flattened body posture and Straub tail. Isapirone induces only a slight flattening of body posture. By contrast, 8-OH-DPAT and 5-MeODMT, but not buspirone and isapirone, and isapirone, also induce forepaw treading, head-weaving and tremor. However, both buspirone and isapirone antagonize the induction of these three behaviors by 8-OH-DPAT or 5-MeODMT. These data show that 8-OH-DPAT and 5-MeODMT are "full agonists" in relation to six components of the 5-HT behavioral syndrome. Buspirone and isapirone, on the other hand, act as "antagonists" in relation to forepaw treading, head-weaving and tremor. Therefore, these data suggest that specific components of the 5-HT behavioral syndrome are mediated by 5-HT1A receptors.