Discriminative Stimulus Effects and 5-HT(2A) Receptors: Evidence for Constitutive Activity
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|Batsell, W. Robert, 1963-
|France, Charles P.
|Kane, Julia N.
|vii, 66 p.
|Serotonin (5-HT) is a monoamine neurotransmitter synthesized in the central nervous system and the gastrointestinal tract. There are 14 known subtypes of the 5-HT receptor. The 5-HT2A subtype of 5-HT receptors is of particular interest because it is widely expressed in the brain and activity at the 5-HT2A receptor mediates behaviors and functions important to humans (Leysen, 2004). Most notably, the 5-HT2A receptor plays a role in depression, schizophrenia, and the actions of hallucinogens. According to classical receptor theory, two types of ligands are believed to bind to a receptor, an agonist or an antagonist (Aloyo et al., 2008). Receptor stimulation takes place only in the presence of an agonist. The antagonist blocks other ligands, like agonists, from binding. However, at some types of receptors, there is a baseline level of receptor stimulation taking place when no ligand is present called constitutive activity. Identifying whether there is constitutive activity at the 5-HT 2A receptor is important for understanding the receptor's relationship to pathologies and the actions of hallucinogens, and for targeting new drug treatments at the 5-HT2A receptor. Studies using associative learning paradigms have provided in vivo evidence for constitutive activity at the 5-HT 2A receptor. Experiments were conducted to establish if evidence for constitutive activity was present in vivo in a drug discrimination behavioral task and found some evidence for constitutive activity at the 5-HT2A receptor. However, in order to further investigate activity at S-HT2A receptors, it was necessary to change the behavioral procedure. In the present study, the efficiency of drug discrimination procedures was improved for the use of investigating activity at the 5-HT 2A receptors. Dose effect curves for a proposed agonist and inverse agonist at the 5-HT 2A receptor were investigated.
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|Discriminative Stimulus Effects and 5-HT(2A) Receptors: Evidence for Constitutive Activity