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The ontogeny of tolerance to the 5-HT1A agonist 8-OH-DPAT: a study in the rat
C E Johansson-Wallsten1, B J Meyerson
1Department of Medical Pharmacology, Uppsala University, Sweden.
Abstract:
The 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) induces hypothermia and a flat body posture in rats. Tolerance 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 micrograms/kg (0.352 mumol/kg) or saline for 1, 4 or 12 days between 22 and 34 days of age. At 26 days of age 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 responses 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.