[3H]Ketanserin (Serotonin Type 2) Binding Increases in Rat Cortex Following Basal Forebrain Lesions with Ibotenic Acid

The response of the serotonergic system following injury to the basal forebrain cholinergic system was investigated in rats. The density of 5-hydroxytryptamine (serotonin) type 2 (S2) receptor sites in the frontal cortex and hippocampus was determined 1 week and 4 months after production of lesions by injections of ibotenic acid into the medial septum and nucleus basalis magnocellularis. One week later, the number of S2 receptor sites in the frontal neocortex, as defined by 3H]ketanserin binding, was unchanged. Four months later, the number of 3H]ketanserin binding sites (and Bmax) was increased and high-affinity 3H]serotonin uptake was decreased in the frontal neocortex, but not in the hippocampus, relative to unlesioned controls. Choline acetyltransferase (acetyl-CoA:choline O-acetyltransferase; EC 2.3.1.6) activity was decreased significantly in the frontal neocortex and hippocampus 1 week and 4 months after surgery. The change in frontal neocortical S2 receptor site density was inversely related to the level of choline acetyltransferase activity, was specific for cholinergic denervation associated with the cortex but not the hippocampus, and may represent a localized denervation supersensitivity due to degeneration of median raphe cortical afferents.