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The activation of 5‐HT 2A receptors in prefrontal cortex enhances dopaminergic activity
Author(s) -
Bortolozzi Analía,
DíazMataix Llorenç,
Scorza M. Cecilia,
Celada Pau,
Artigas Francesc
Publication year - 2005
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2005.03485.x
Subject(s) - ventral tegmental area , prefrontal cortex , neuroscience , dopaminergic , dopamine , chemistry , agonist , ritanserin , excitatory postsynaptic potential , receptor , glutamate receptor , stimulation , 5 ht receptor , serotonin , inhibitory postsynaptic potential , psychology , biochemistry , cognition
Atypical antipsychotics show preferential 5‐HT 2A versus dopamine (DA) D 2 receptor affinity. At clinical doses, they fully occupy cortical 5‐HT 2 receptors, which suggests a strong relationship with their therapeutic action. Half of the pyramidal neurones in the medial prefrontal cortex (mPFC) express 5‐HT 2A receptors. Also, neurones excited through 5‐HT 2A receptors project to the ventral tegmental area (VTA). We therefore hypothesized that prefrontal 5‐HT 2A receptors can modulate DA transmission through excitatory mPFC–VTA inputs. In this study we used single unit recordings to examine the responses of DA neurones to local (in the mPFC) and systemic administration of the 5‐HT 2A/2C agonist 1‐[2,5‐dimethoxy‐4‐iodophenyl‐2‐aminopropane] (DOI). Likewise, using microdialysis, we examined DA release in the mPFC and VTA (single/dual probe) in response to prefrontal and systemic drug administration. The local (in the mPFC) and systemic administration of DOI increased the firing rate and burst firing of DA neurones and DA release in the VTA and mPFC. The increase in VTA DA release was mimicked by the electrical stimulation of the mPFC. The effects of DOI were reversed by M100907 and ritanserin. These results indicate that the activity of VTA DA neurones is under the excitatory control of 5‐HT 2A receptors in the mPFC. These observations may help in the understanding of the therapeutic action of atypical antipsychotics.