Although speculative, the agonist activity of aripiprazole at the 5-HT1A receptor may be relevant to its differential effect on hippocampal volume compared with other antipsychotic agents examined by Bodnar and colleagues. The 5-HT1A receptors are major inhibitory G-protein-coupled receptor subtypes found on pre- and post-synaptic neurons throughout the brain. They are highly expressed in brain regions implicated in affect regulation and memory processing, including the hippocampus, particularly in the CA1 region, the amygdala and in the frontal, cingulate and entorhinal cortices.
11 5-HT1A receptors influence dopaminergic, cholinergic, glutamatergic and GABAergic functions. In this context, 5-HT1A receptor agonists have been considered as potentially pro-cognitive on the basis of preclinical evidence that they modulate the release of cortical and hippocampal dopamine and acetylcholine.
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