CHANGES IN THE ANXIOLYTIC EFFECT OF 5-HT1 A AGONISTS ACCORDING TO SPECIES, AGE, GENDER AND ENDOCRINOUS STATE OF THE INDIVIDUAL

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-HT1A receptor) such as buspirone, indor enate, 8-OH-DPAT and ipsapirone. In these series of experiments we use d the conditioned defensive burying behaviour paradigm to establish th e anxiety levels. Although we have examined diverse anxiety paradigms in our laboratory, we selected this model because it offers several ad vantages. The interspecies results show that in rats, hamsters and mic e, all 5-HT1A agonists produce a clear anxiolytic effect. However, the mechanism underlying such action seems to vary depending upon the spe cies: thus, in mice and hamsters, the 5-HT system appears to be direct ly involved, while in rats the reduction in anxiety after these compou nds appears to be mediated via the central noradrenergic system. Inter estingly, differences in the effects of these drugs along various ages were found. Thus, in infant rats (2-3 weeks) all 5-HT1A agonists prov ed to be ineffective, but a gradual increase of their anxiolytic actio n was observed between the 5th. and 13th. weeks. On the 21st. week of age a less consistent anxiolytic action of these drugs was observed. I n relation to the gender, in the present experiments we did not find a statistical significant difference in the anxiolytic effects of buspi rone, ipsapirone, indorenate and 8-OH-DPAT between males and females o r between females in different phases of their estrous cycle; however, diazepam produced clearer actions in male rats when compared to femal es. Such disparities were particularly conspicuous when comparing male s with female rats in their metestrous endocrine phase. In this respec t it is interesting that during the rat estrous cycle different basal levels of anxiety were found: relatively low in the proestrous phase a nd high in the metestrous/diestrus phases. As before mentioned, no gen der difference in the antianxiety actions of the 5-HT1A agonists were observed; however, in females in proestrous and in males, diazepam, in dorenate and ipsapirone induced a decrease in the rats reactivity. Fin ally, the present review shows that 8-OH-DPAT looses its anxiolytic pr operties in 7-days lactating mothers. All data taken together reveal t he strong influence that the internal physiological state may have on the pharmacological actions of anxiolytics. Additionally, these result s indicate that the physiological condition should be considered when anxiolytics are clinically used.