Differential effects of 5-hydroxytryptamine1a selective drugs on the 5-HT behavioral syndrome.
Pharmacology, biochemistry, and behavior – June 01, 1986
Source: PubMed
Summary
8-OH-DPAT and 5-MeODMT significantly activate six components of the serotonin behavioral syndrome in rats, while buspirone and isapirone counteract certain effects. In tests with rat brain membranes, these drugs showed potent inhibition of binding, with Ki values ranging from 1.9 to 13 nM. Specifically, 8-OH-DPAT and 5-MeODMT triggered behaviors like forepaw treading and tremors, whereas buspirone and isapirone only slightly affected body posture. This highlights the complex role of 5-HT1A receptors in mediating serotonin-related behaviors.
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.