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The prefrontal cortex (PFC) is enriched in several serotonin receptors, including 5-HT 1A -R, 5-HT 2A -R, and 5-HT 3 -R. These receptors modulate PFC activity due to their expression in large neuronal populations (5-HT 1A -R, 5-HT 2A -R) or in selected GABAergic populations (5-HT 3 -R). They are also relevant for antidepressant and antipsychotic drug action. Less is known about the localization of 5-HT 2C -R, for which atypical antipsychotics show high affinity. Here, we report on the cellular distribution of 5-HT 2C -R in rat PFC and striatum, using double in situ hybridization histochemistry. In PFC, 5-HT 2C -R are expressed in pyramidal (VGLUT1-positive) and GABAergic (GAD-positive) neurons, including parvalbumin-positive neurons. There is a marked dorso-ventral gradient in the proportion of VGLUT1-positive cells expressing 5-HT 2C -R (9% in the cingulate cortex, 61% in the tenia tecta and 66% in the piriform cortex), less marked for GABAergic neurons (13–27%). There is also a laminar gradient, with more cells expressing 5-HT 2C -R in deep (V–VI) than in intermediate (II–III) layers. In common with 5-HT 3 -R, layer I GABAergic cells express 5-HT 2C -R. The proportion of 5-HT 2C -R-expressing striatal neurons was 23% (dorsolateral caudate-putamen), 37% (ventromedial caudate-putamen), 53% (nucleus accumbens-core), and 49% (nucleus accumbens-shell). These results help to better understand the serotonergic modulation of PFC-based networks, including basal ganglia circuits, and atypical antipsychotic drug action.

Expression of Serotonin 2C Receptors in Pyramidal and GABAergic Neurons of Rat Prefrontal Cortex: A Comparison with Striatum