Figure 1. Genetic deletion of PSD-95 results in a selective loss of 5-HT_2A and 5-HT_2C receptors.

(A) 5-HT_2A and PSD-95 double-label immunochemistry in medial prefrontal cortex of PSD-95^wildtype and PSD-95^null mice shows a large reduction in 5-HT_2A receptor expression in null mice (N=3 littermate pairs). (B) 5-HT_2C immunochemistry in PSD-95^wildtype and PSD-95^null striatum and hippocampus reveals that 5-HT_2C receptor expression is almost completely abolished in the absence of PSD-95 in both striatum and hippocampus (N=3 littermate pairs). (C) Comparison of B_max estimates for the 5-HT_2A receptor (N=4 littermate pairs) and the 5-HT_1A receptor (N=5 littermate pairs) in PSD-95^wildtype and PSD-95^null cortices. B_max estimates were obtained by performing [³H]-ketanserin (5-HT_2A) and [³H]-WAY100635 (5- HT_1A) saturation binding on microdissected and homogenized cortical tissue. Quantitation showed a roughly 40% reduction in 5-HT_2A expression and no change in 5-HT_1A expression in the cortices of PSD-95^null mice. (D) Comparison of B_max estimates for the 5-HT_2C receptor (N=3; tissue from 3 animals was pooled for each measurement, for a total of 9 animals, all littermate pairs) and 5-HT_1A receptor (N=6 littermate pairs) in PSD-95^wildtype and PSD-95^null hippocampi. B_max estimates were obtained by performing [³H]-mesulergine saturation binding in the presence of 100 nM spiperone to block the vast majority of 5-HT_2A receptors (5- HT_2C) and [³H]-WAY100635 saturation binding (5-HT_1A). Quantitation showed an almost 70% reduction in 5-HT_2C expression and no change in 5-HT_1A expression in hippocampus in the absence of PSD-95. All saturation binding was analyzed using non-linear least squares fitting. B_max data are presented as means +/- SEM. ^*p < .05, ^**p < .01, ^***p < .001; one-tailed unpaired t-test.