Regulating Prefrontal Cortex Activation: An Emerging Role for the 5-HT 2A Serotonin Receptor in the Modulation of Emotio
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Regulating Prefrontal Cortex Activation: An Emerging Role for the 5-HT2A Serotonin Receptor in the Modulation of Emotion-Based Actions? Susana Aznar & Anders B. Klein
Received: 1 March 2013 / Accepted: 6 May 2013 # Springer Science+Business Media New York 2013
Abstract The prefrontal cortex (PFC) is involved in mediating important higher-order cognitive processes such as decision making, prompting thereby our actions. At the same time, PFC activation is strongly influenced by emotional reactions through its functional interaction with the amygdala and the striatal circuitry, areas involved in emotion and reward processing. The PFC, however, is able to modulate amygdala reactivity via a feedback loop to this area. A role for serotonin in adjusting for this circuitry of cognitive regulation of emotion has long been suggested based primarily on the positive pharmacological effect of elevating serotonin levels in anxiety regulation. Recent animal and human functional magnetic resonance studies have pointed to a specific involvement of the 5-hydroxytryptamine (5-HT)2A serotonin receptor in the PFC feedback regulatory projection onto the amygdala. This receptor is highly expressed in the prefrontal cortex areas, playing an important role in modulating cortical activity and neural oscillations (brain waves). This makes it an interesting potential pharmacological target for the treatment of neuropsychiatric modes characterized by lack of inhibitory control of emotion-based actions, such as addiction and other impulserelated behaviors. In this review, we give an overview of the 5-HT2A receptor distribution (neuronal, intracellular, and anatomical) along with its functional and physiological effect on PFC activation, and how that relates to more recent S. Aznar (*) Laboratory for Stereology and Neuroscience, University Hospital Bispebjerg, Building 11B, 2nd Floor, Bispebjerg Bakke 23, 2400 Copenhagen, NV, Denmark e-mail: [email protected] A. B. Klein Department of Drug Design and Pharmacology, University of Copenhagen, Copenhagen, Denmark
findings of a regulatory effect of the PFC on the emotional control of our actions. Keywords Serotonin receptor . Molecular neurobiology . Stress . Anxiety . Decision making . Intracellular modulation . Neuronal plasticity
Introduction The 5-hydroxytryptamine (5-HT)2A serotonin receptor has long received attention in relation to a range of cognitiverelated neuropsychiatric disorders, with the most prominent being schizophrenia and borderline personality disorders [1–12]. This arises from the fact that atypical antipsychotics demonstrate high affinity for the 5-HT2A receptor (reviewed in [1, 13]) as well as animal studies describing a hallucinogenic effect of the 5-HT2A receptor activation mediated by the medial prefrontal cortex (mPFC) [14–16]. The 5-HT2A receptor level changes described in these patient groups have primarily been observed in the prefrontal cortex (PFC) regions [2, 8, 11]. Receptor binding differences or functional dysregulation of this receptor in the PFC
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