Mapping of CBV changes in 5-HT(1A) terminal fields by functional MRI in the mouse brain.
Visualization of brain activity in humans and animals using functional magnetic resonance imaging (fMRI) is an established method for translational neuropsychopharmacology. It is useful to study the activity of defined brain structures, however it requires further refinement to allow more specific cellular analyses, like for instance, the activity of selected pools of brain cells. Here, we investigated brain activity in serotonergic pathways in the adult mouse brain by using acute pharmacological challenge of 5-hydroxytryptamine (5-HT) 1A receptors. We show that administration of the 5-HT(1A) receptor agonist 8-OH-DPAT prompts a dose-dependent reduction in local cerebral blood volume (CBV) in brain areas rich in neurons expressing post-synaptic 5-HT(1A) receptor, including the prefrontal cortex, hippocampus and amygdalar nuclei. Region-specific inhibition of the response by co-injection of 8-OH-DPAT with the selective 5-HT(1A) receptor antagonist WAY-100635, or in 5-HT(1A) knock-out mice, suggests that 5-HT(1A) receptors are the primary targets of the agonist. Overall, the data demonstrate the feasibility of mapping region-specific serotonergic transmission in the adult mouse brain in vivo by non-invasive fMRI. The method opens novel perspectives for investigating 5-HT(1A) receptor functions in mouse models of human pathologies resulting from a dysfunction of the 5-HT(1A) receptor or the serotonergic system, including depression and anxiety.
Mueggler
Thomas
T
Institute for Biomedical Engineering, University and ETH Zurich, Zurich, Switzerland. thomas.mueggler@roche.com
Razoux
Florence
F
Russig
Holger
H
Buehler
Anna
A
Franklin
Tamara B
TB
Baltes
Christof
C
Mansuy
Isabelle M
IM
Rudin
Markus
M
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000008:administration & dosage / Q000494:pharmacology; D019412:Anatomy, Cross-Sectional; D000818:Animals; D001921:Brain / Q000033:anatomy & histology / Q000098:blood supply* / Q000187:drug effects / Q000502:physiology*; D001931:Brain Mapping / Q000379:methods*; D004305:Dose-Response Relationship, Drug; D005240:Feasibility Studies; D007700:Kinetics; D008279:Magnetic Resonance Imaging; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D010879:Piperazines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D044282:Receptor, Serotonin, 5-HT1A / Q000235:genetics / Q000378:metabolism*; D012039:Regional Blood Flow / Q000187:drug effects*; D058825:Serotonin 5-HT1 Receptor Agonists / Q000008:administration & dosage / Q000494:pharmacology; D058829:Serotonin 5-HT1 Receptor Antagonists / Q000494:pharmacology
D009419:Nerve Tissue Proteins; D010879:Piperazines; D011725:Pyridines; D058825:Serotonin 5-HT1 Receptor Agonists; D058829:Serotonin 5-HT1 Receptor Antagonists; D044282:Receptor, Serotonin, 5-HT1A; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin