Cambios en el efecto ansiolitico de los agonistas 5-HT(1A) de acuerdo con la especie, la edad, el genero y el estado endocrino del individuo

In this paper we review the relevance of gender, species, age and some endocrine features on the anxiolytic action of certain serotonergic (5-HT) drugs (agonists at the 5-HT(1A) receptor) such as buspirone, indorenate, 8-OH-DPAT and ipsapirone. In these series of experiments we used the conditioned defensive burying behaviour paradigm to establish the anxiety levels. Although we have examined diverse anxiety paradigms in our laboratory, we selected this model because it offers several advantages. The interspecies results show that in rats, hamsters and mice, all 5-HT(1A) agonists produce a clear anxiolytic effect. However, the mechanism underlying such action seems to vary depending upon the species: thus, in mice and hamsters, the 5-HT system appears to be directly involved, while in rats the reduction in anxiety after these compounds appears to be mediated via the contral noradrenergic system. Interestingly, differences in the effects of these drugs along various ages were found. Thus, in infant rats (2-3 weeks) all 5-HT(1A) agonists proved to be ineffective, but a gradual increase of their anxiolytic action was observed between the 5th. and 13th. weeks. On the 21st. week of age a less consistent anxiolytic action of these drugs was observed. In relation to the gender, in the present experiments we did not find a statistical significant difference in the anxiolytic effects of buspirone, ipsapirone, indorenate and 8-OH-DPAT between males and females or between females in different phases of their estrous cycle; however, diazepam produced clearer actions in male rats when compared to females. Such disparities were particularly conspicuous when comparing males with female rats in their metestrous endocrine phase. In this respect it is interesting that during the rat estrous cycle different basal levels of anxiety were found: relatively low in the proestrous phase and high in the metestrous/diestrus phases. As before mentioned, no gender difference in the antianxiety actions of the 5-HT(1A) agonists were observed; however, in females in proestrous and in males, diazepam, indorenate and ipsapirone induced a decrease in the rats reactivity. Finally, the present review shows that 8-OH-DPAT looses its anxiolytic properties in 7-days lactating mothers. All data taken together reveal the strong influence that the internal physiological state may have on the pharmacological actions of anxiolytics. Additionally, these results indicate that the physiological condition should be considered when anxiolytics are clinically used.