Repeated DOI and SR 46349B treatments do not affect elevated plus-maze anxiety despite opposite effects on cortical 5-HT2A receptors.

We report the consequences of a 4-day treatment (b.i.d) with the 5-HT2A,2B,2C receptor agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI, 1.5 mg/kg) or the selective 5-HT2A receptor antagonist trans-4-[(3Z)3-(2-dimethylaminoethyl)oxyimino-3-(2-fluorophe nyl)propen-1-yl]phenol hemifumarate (SR 46349B, 7.5 mg/kg) on (i) anxiety-related behaviour in an elevated plus-maze, and (ii) specific [3H]ketanserin binding at central 5-HT2A receptors, in Roman rats. Neither DOI nor SR 46349B pretreatment affected the behaviour in the open arms of the elevated plus-maze; however, DOI pretreatment promoted discrete changes in the closed arm entries. The Bmax value of [3H]ketanserin binding at cortical 5-HT2A receptors was decreased by repeated DOI pretreatment. Conversely, Bmax, but also KD, values were increased by SR 46349B pretreatment. Thus, changes at central 5-HT2A receptors may occur without there being changes in anxiety-related behaviour in the elevated plus-maze.