Cerebral ischaemia reduces the density of 5-HT2 binding sites in the frontal cortex of the gerbil.

The 5-HT2 antagonist [3H]ketanserin labels a single population of high affinity sites (Kd 0.48 +/- 0.03 nM; Bmax 206 +/- 20 fmol/mg protein) in the frontal cortex of the gerbil. Specific binding of [3H]ketanserin was displaced by a number of 5-HT2A antagonists ritanserin, cyproheptadine and methysergide) but not by the 5-HT1A agonist, 8-hydroxy-2-(di-n- propylamino)tetralin (8-OH-DPAT) or the 5-HT1A/1B agonists 5-carboxyamidotryptamine (5-CT) or RU 24969, indicating that the labelled site probably represents the 5-HT2 receptor. Cerebral ischaemia induced in either a 3 hr unilateral non-recovery model or a 5 min bilateral, 3-day recovery model, resulted in a significant decrease in the density of 5-HT2 binding sites in the ischaemic frontal cortex without an apparent change in their affinity for the ligand. The decrease in density was not simply related to levels of 5-HT because occlusion of the right carotid artery for 3 hr resulted in bilateral depletion of 5-HT but only in an ipsilateral reduction in the density of binding sites. In addition, a significant decrease in the density of 5-HT2 binding sites occurred in the recovery model at a time when the levels of 5-HT in the cortex were unaltered.