FLESINOXAN PRETREATMENT DIFFERENTIALLY AFFECTS CORTICOSTERONE, PROLACTIN AND BEHAVIORAL-RESPONSES TO A FLESINOXAN CHALLENGE

To determine whether alterations in 5-HT1A receptor mediated responses induced by a single injection with a selective 5-HT1A receptor agonis t is a transient effect, or whether the (de)sensitisation is more pers istent, rats were pretreated with the selective and full 5-HT1A recept or agonist, flesinoxan (3 mg/kg SC once daily) for either 1 day or 1 w eek. Twenty-four hour after the last pretreatment injection, rats were challenged with flesinoxan (3 mg/kg SC), and the effects on plasma co rticosterone and prolactin levels, lower lip retraction and behaviour in the shock-probe burying test were determined. Several 5-HT1A recept or mediated responses were modified differentially following the flesi noxan pretreatment. However, all changes induced by a single flesinoxa n injection remained present upon repeated flesinoxan administration. The differential changes in the responses to flesinoxan cannot easily be explained by differences in pre- or postsynaptically 5-HT1A mediate d responses. The prolactin response to flesinoxan, which is thought to be mediated postsynaptically, was enhanced, whereas the corticosteron e response to flesinoxan, which is also mediated postsynaptically, was attenuated. The presynaptically mediated lower lip retraction respons e was attenuated as well, whereas the behavioural effects of flesinoxa n remained relatively unaffected following repeated flesinoxan adminis tration. Upon prolonged flesinoxan pretreatment, the changes induced b y a single flesinoxan injection remained present or increased further. Although repeated flesinoxan administration (1 day and 1 week) result ed in 20% lower plasma flesinoxan concentrations, this effect could no t explain the neuroendocrine and behavioural findings.