DOI-Induced Activation of the Cortex: Dependence on 5-HT2AHeteroceptors on Thalamocortical Glutamatergic Neurons
Journal of Neuroscience December 1, 2000 Jennifer L. Scruggs, Sachin Patel, Michael Bubser et al. 154 citations
A hallucinogenic drug that activates 5-HT2A receptors increases Fos protein expression in the rat somatosensory cortex. This effect depends on 5-HT2A, not 5-HT2C, receptors and requires intact thalamocortical connections. The drug does not act directly on cortical neurons but instead stimulates 5-HT2A receptors on thalamocortical neurons, increasing glutamate release, which then drives Fos expression in cortical neurons via AMPA receptors. Blocking AMPA/KA receptors or lesioning the ventrobasal thalamus reduces the effect. These findings illuminate how hallucinogens produce their effects through a thalamocortical glutamate pathway.