THE ONTOGENY OF TOLERANCE TO THE 5-HT1A AGONIST 8-OH-DPAT - A STUDY IN THE RAT

The 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8- OH-DPAT) induces hypothermia and a flat body posture in rats. Toleranc e to 8-OH-DPAT develops in adult rats with regard to these responses. The ontogeny of the ability to induce tolerance to the hypothermia and the flat body posture elicited by 8-OH-DPAT was studied. Rat pups of both sexes were given 8-OH-DPAT, 100 mu g/kg (0.352 mu mol/kg) or sali ne for 1, 4 or 12 days between 22 and 34 days of age. At 26 days of ag e no attenuation was induced by treatment during the previous 4 days. In contrast, at 34 days of age there was a clear attenuation of both r esponses induced by 8-OH-DPAT after an analogous 4 day treatment. The data indicate that the ability to induce tolerance to 8-OH-DPAT is not developed before 26 days of age in the rat.