Co-expression and in vivo interaction of serotonin1A and serotonin2A receptors in pyramidal neurons of prefrontal cortex.
The prefrontal cortex plays a key role in the control of higher brain functions and is involved in the pathophysiology and treatment of schizophrenia. Here we report that approximately 60% of the neurons in rat and mouse prefrontal cortex express 5-HT(1A) and/or 5-HT2A receptor mRNAs, which are highly co-localized (approximately 80%). The electrical stimulation of the dorsal and median raphe nuclei elicited 5-HT1A-mediated inhibitions and 5-HT2A-mediated excitations in identified pyramidal neurons recorded extracellularly in rat medial prefrontal cortex (mPFC). Opposite responses in the same pyramidal neuron could be evoked by stimulating the raphe nuclei at different coordinates, suggesting a precise connectivity between 5-HT neuronal subgroups and 5-HT1A and 5-HT2A receptors in pyramidal neurons. Microdialysis experiments showed that the increase in local 5-HT release evoked by the activation of 5-HT2A receptors in mPFC by DOI (5-HT2A/2C receptor agonist) was reversed by co-perfusion of 5-HT1A agonists. This inhibitory effect was antagonized by WAY-100635 and the prior inactivation of 5-HT1A receptors in rats and was absent in mice lacking 5-HT1A receptors. These observations help to clarify the interactions between the mPFC and the raphe nuclei, two key areas in psychiatric illnesses and improve our understanding of the action of atypical antipsychotics, acting through these 5-HT receptors.
Amargós-Bosch
Mercè
M
Department of Neurochemistry, Institut d'Investigacions Biomèdiques de Barcelona (CSIC), IDIBAPs, Barcelona, Spain.
Bortolozzi
Analía
A
Puig
M Victoria
MV
Serrats
Jordi
J
Adell
Albert
A
Celada
Pau
P
Toth
Miklos
M
Mengod
Guadalupe
G
Artigas
Francesc
F
D000662:Amphetamines / Q000494:pharmacology; D000818:Animals; D001345:Autoradiography; D004298:Dopamine / Q000502:physiology; D004558:Electric Stimulation; D017403:In Situ Hybridization; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017551:Microdialysis; D017397:Prefrontal Cortex / Q000166:cytology* / Q000378:metabolism*; D017966:Pyramidal Cells / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D011903:Raphe Nuclei / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D044282:Receptor, Serotonin, 5-HT1A / Q000096:biosynthesis* / Q000235:genetics; D044402:Receptor, Serotonin, 5-HT2A / Q000096:biosynthesis*; D012701:Serotonin / Q000502:physiology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D017557:Ventral Tegmental Area / Q000166:cytology / Q000378:metabolism
D000662:Amphetamines; D012333:RNA, Messenger; D044402:Receptor, Serotonin, 5-HT2A; D017366:Serotonin Receptor Agonists; D044282:Receptor, Serotonin, 5-HT1A; D012701:Serotonin; C015952:4-iodo-2,5-dimethoxyphenylisopropylamine; D004298:Dopamine