Discriminative Stimulus Effects and 5-HT(2A) Receptors: Evidence for Constitutive Activity
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Authors
Kane, Julia N.
Issue Date
2008
Type
Thesis
Language
en_US
Keywords
Alternative Title
Abstract
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.
Description
vii, 66 p.
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