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The action of serotonin (5-HT) at the 5-HT(2A) receptor subtype is thought to be involved in cocaine-seeking behavior that is motivated by exposure to drug-associated cues and drug priming. 5-HT(2A) receptors are densely clustered in the ventromedial prefrontal cortex (vmPFC), an area that plays a role in mediating cocaine-seeking behavior.

Blockade of 5-HT2A receptors in the medial prefrontal cortex attenuates reinstatement of cue-elicited cocaine-seeking behavior in rats