Control of dorsal raphe serotonergic neurons by the medial prefrontal cortex: Involvement of serotonin-1A, GABA(A), and glutamate receptors.
Anatomical evidence indicates that medial prefrontal cortex (mPFC) neurons project to the dorsal raphe nucleus (DR). In this study, we functionally characterized this descending pathway in rat brain. Projection neurons in the mPFC were identified by antidromic stimulation from the DR. Electrical stimulation of the mPFC mainly inhibited the activity of DR 5-HT neurons (55 of 66). Peristimulus time histograms showed a silence of 150 +/- 9 msec poststimulus (latency, 36 +/- 1 msec). The administration of WAY-100635 and picrotoxinin partly reversed this inhibition, indicating the involvement of 5-HT(1A) and GABA(A) receptors. In rats depleted of 5-HT with p-chlorophenylalanine, the electrical stimulation of mPFC mainly activated 5-HT neurons (31 of 40). The excitations (latency, 17 +/- 1 msec) were antagonized by MK-801 and NBQX. Likewise, MK-801 prevented the rise in DR 5-HT release induced by electrical stimulation of mPFC. The application of 8-OH-DPAT in mPFC significantly inhibited the firing rate of DR 5-HT neurons and, in dual-probe microdialysis experiments, reduced the 5-HT output in mPFC and DR. Furthermore, the application of WAY-100635 in mPFC significantly antagonized the reduction of 5-HT release produced by systemic 8-OH-DPAT administration in both areas. These results indicate the existence of a complex regulation of DR 5-HT neurons by mPFC afferents. The stimulus-induced excitation of some 5-HT neurons by descending excitatory fibers releases 5-HT, which inhibits the same or other DR neurons by acting on 5-HT(1A) autoreceptors. Afferents from the mPFC also inhibit 5-HT neurons through the activation of GABAergic interneurons. Ascending serotonergic pathways may control the activity of this descending pathway by acting on postsynaptic 5-HT(1A) receptors.
Celada
P
P
Department of Neurochemistry, Institut d' Investigacions Biomèdiques de Barcelona, Consejo Superior de Investigaciones Cientificas (Institut d'Investigacions Biomèdiques August Pi i Sunyer), 08036 Barcelona, Spain.
Puig
M V
MV
Casanovas
J M
JM
Guillazo
G
G
Artigas
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F
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000818:Animals; D017660:Autoreceptors / Q000378:metabolism; D002404:Catheterization; D004558:Electric Stimulation; D005071:Evoked Potentials / Q000502:physiology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D058787:GABA-A Receptor Antagonists; D008297:Male; D017551:Microdialysis; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D009434:Neural Pathways / Q000502:physiology; D009474:Neurons / Q000145:classification / Q000187:drug effects / Q000378:metabolism*; D017397:Prefrontal Cortex / Q000187:drug effects / Q000502:physiology*; D011903:Raphe Nuclei / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time / Q000502:physiology; D011963:Receptors, GABA-A / Q000378:metabolism; D017470:Receptors, Glutamate / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000378:metabolism; D017981:Receptors, Neurotransmitter / Q000819:agonists / Q000378:metabolism*; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism; D044263:Receptors, Serotonin, 5-HT1; D012701:Serotonin / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology
D017660:Autoreceptors; D018691:Excitatory Amino Acid Antagonists; D018756:GABA Antagonists; D058787:GABA-A Receptor Antagonists; D011963:Receptors, GABA-A; D017470:Receptors, Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D012701:Serotonin; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin