Regulation of serotonin release by γ-aminobutyric acid (GABA) and glutamate was examined by microdialysis in unanaesthetized rats. The GABAA receptor agonist muscimol, or the glutamate receptor agonists kainate, γ-amino-3-hydroxy-5-methyl-4-isoxazolaproprionate or N-methyl-D-aspartate were infused into the dorsal raphe nucleus (DRN) while extracellular serotonin was measured in the DRN and nucleus accumbens. Muscimol produced decreases, and the glutamate receptor agonists produced increases in serotonin. To determine if these receptors have a tonic influence on serotonergic neurons, glutamate or GABAA receptor antagonists were infused into the DRN. Kynurenate, a nonselective glutamate receptor blocker, produced a small, 30% decrease in serotonin. A similar decrease was obtained with combined infusion of AP-5 and DNQX into the DRN. The GABAA receptor blocker bicuculline produced an approximately three-fold increase in DRN serotonin. In conclusion, glutamate neurotransmitters have a weak tonic excitatory influence on serotonergic neurons in the rat DRN. However, the predominate influence is mediated by GABAA receptors.
Adell A , Artigas F (1998) A microdialysis study of the in vivo release of 5-HT in the median raphe nucleus of the rat . Br J Pharmacol125: 1361-1367
2.
Adell A , Carceller A , Artigas F (1993) In vivo brain dialysis study of the somatodendritic release of serotonin in the Raphe nuclei of the rat: effects of 8-hydroxy-2-(di-n-propylamino)tetralin . J Neurochem60: 1673-1681
3.
Barnard E A (1997) Ionotropic glutamate receptors: new types and new concepts . Trends Pharmacol Sci18: 141-148
4.
Becquet D , Hery M , Deprez P , Faudon M , Fache M P , Giraud P , Hery F (1993) N-Methyl-D-aspartic acid/glycine interactions on the control of 5-hydroxytryptamine release in raphe primary cultures . J Neurochem61: 1692-1697
5.
Bettler B , Mulle C (1995) Review: neurotransmitter receptors. II. AMPA and kainate receptors . Neuropharmacology34: 123-139
6.
Bosker F , Klompmakers A , Westenberg H (1994) Extracellular 5-hydroxytryptamine in median raphe nucleus of the conscious rat is decreased by nanomolar concentrations of 8-hydroxy-2(di-n-propylamino) tetralin and is sensitive to tetrodotoxin . J Neurochem63: 2165-2171
7.
Bristow L J , Hutson P H , Thorn L , Tricklebank M D (1993) The glycine/NMDA receptor antagonist, R-(+)-HA-966, blocks activation of the mesolimbic dopaminergic system induced by phencyclidine and dizocilpine (MK-801) in rodents . Br J Pharmacol108: 1156-1153
8.
Brodin E , Linderoth B , Goiny M , Yamamoto Y , Gazelius B , Millhorn D E , Hokfelt T , Ungerstedt U (1990) In vivo release of serotonin in cat dorsal vagal complex and cervical ventral horn induced by electrical stimulation of the medullary raphe nuclei . Brain Res535: 227-236
9.
Buller A L , Larson H C , Schneider B E , Beaton J A , Morrisett R A , Monaghan D T (1994) The molecular basis of NMDA receptor subtypes: native receptor diversity is predicted by subunit composition . J Neurosci14: 5471-5484
10.
Carboni E , DiChiara G (1989) Serotonin release estimated by transcortical dialysis in freely moving rats . Neuroscience32: 637-645
11.
Debarbieux F , Brunton J , Charpak S (1998) Effect of bicuculline on thalamic activity: a direct blockade of IAHP in reticularis neurons . J Neurophysiol79: 2911-2918
12.
DeBoer P , Abercrombie E D (1996) Physiological release of striatal acetylcholine in vivo: modulation by D1 and D2 dopamine receptor subtypes . J Pharmacol Exp Ther277: 775-783
13.
Dykstra K H , Hsiao J K , Morrison PF , Bungay P M , Mefford IN , Scully M M , Dedrick R L (1992) Quantitative examination of tissue concentration profiles associated with microdialysis . J Neurochem58: 931-940
14.
Ellison G (1995) The N-methyl-D-aspartate antagonists phencyclidine, ketamine and dizocilpine as both behavioral and anatomical models of the dementias . Brain Res Rev20: 250-267
15.
French E D (1994) Phencyclidine and the midbrain dopamine system: electrophysiology and behavior . Neurotox Teratol16: 355-362
16.
Gallager D W , Aghajanian G K (1976) Effect of antipsychotic drugs on the firing of dorsal raphe cells. 2. Reversal by picrotoxin . Eur J Pharmacol39: 357-364
17.
Gartside S E , Umbers V , Hajos M , Sharp T (1995) Interaction between a selective 5-HT1A receptor antagonist and an SSRI in vivo: effects on 5-HT cell firing and extracellular 5-HT . Br J Pharmacol115: 1064-1070
18.
Grant K A , Colombo G , Grant J , Rogawski M A (1996) Dizocilpinelike discriminative stimulus effects of low-affinity uncompetitive NMDA antagonists . Neuropharmacology35: 1709-1719
19.
Hajos M , Richards C D , Szekely A D , Sharp T (1998) An electrophysiological and neuroanatomical study of the medial prefrontal cortical projection to the midbrain raphe nuclei in the rat . Neuroscience87: 95-108
20.
Hall R A , Kessler M , Lynch G (1994) Kainate binding to the AMPA receptor in rat brain . Neurochem Res19: 777-782
21.
Hernandez L , Auerbach S , Hoebel B G (1988) Phencyclidine (PCP) injected in the nucleus accumbens increases extracellular dopamine and serotonin as measured by microdialysis . Life Sci42: 1713-1723
22.
Hjorth S , Auerbach S B (1994) Further evidence for the importance of 5-HT1A autoreceptors in the action of selective serotonin reuptake inhibitors . Eur J Pharmacol260: 251-255
23.
Hutson P H , Sarna G S , O'Connell M T , Curzon G (1989) Hippocampal 5-HT synthesis and release in vivo is decreased by infusion of 8-OHDPAT into the nucleus raphe dorsalis . Neurosci Lett100: 276-280
24.
Jacobs B L , Azmitia E C (1992) Structure and function of the brain serotonin system . Physiol Rev72: 165-229
25.
Jacobs B L , Fornal C A (1991) Activity of brain serotonergic neurons in the behaving animal . Pharmacol Rev43: 563-578
26.
Jolas T , Aghajanian G K (1997) Opioids suppress spontaneous and NMDA-induced inhibitory postsynaptic currents in the dorsal raphe nucleus of the rat in vitro . Brain Res755: 229-245
27.
Jolas T , Gilden L , Nestler E , Aghajanian G K (1998) Opioid upregulation of adenylyl cyclase linked to GABA tone in 5-HT dorsal raphe neurons . Soc Neurosci Abstr24: 1352-1352
28.
Kalén P , Strecker R E , Rosengren E , Bjorklund A (1988) Endogenous release of neuronal serotonin and 5-hydroxyindoleacetic acid in the caudate-putamen of the rat as revealed by intracerebral dialysis coupled to high-performance liquid chromatography with fluorimetric detection . J Neurochem51: 1422-1435
29.
Kalén P , Strecker R E , Rosengren E , Bjorklund A (1989) Regulation of striatal serotonin release by the lateral habenula-dorsal raphe pathway in the rat as demonstrated by in vivo microdialysis: role of excitatory amino acids and GABA . Brain Res492: 187-202
30.
Levine E S , Jacobs B L (1992) Neurochemical afferents controlling the activity of serotonergic neurons in the dorsal raphe nucleus: microiontophoretic studies in the awake cat . J Neurosci12: 4037-4044
31.
Maier S F , Grahn R E , Maswood S , Watkins L R (1995) The benzodiazepine receptor antagonists flumazenil and CGS8216 block the enhancement of fear conditioning and interference with escape behavior produced by inescapable shock . Psychopharmacology121: 250-258
32.
Marsden C A , Martin K F , Routledge C , Brazell M P , Maidment N T (1986) Application of intracerebral dialysis and in vivo voltammetry to pharmacological and physiological studies of amine neurotransmitters . Ann NY Acad Sci473: 106-125
33.
Martin P , Carlsson M L , Hjorth S (1998) Systemic PCP treatment elevates brain extracellular 5-HT: a microdialysis study in awake rats . Neuroreport9: 2985-2988
34.
Matos F F , Urban C , Yocca F D (1996) Serotonin (5-HT) release in the dorsal raphe and ventral hippocampus: raphe control of somatodendritic and 5-HT release . J Neural Transm103: 173-190
35.
McQuade R , Sharp T (1995) Release of cerebral 5hydroxytryptamine evoked by electrical stimulation of the dorsal and median raphe nuclei: effect of a neurotoxic amphetamine . Neuroscience68: 1079-1088
36.
Moghaddam B , Adams B , Verma A , Daly D (1997) Activation of glutamatergic neurotransmission by ketamine: a novel step in the pathway from NMDA receptor blockade to dopaminergic and cognitive disruptions associated with the prefrontal cortex . J Neurosci17: 2921-2927
37.
Nishikawa T , Scatton B (1983) Evidence for a GABAergic inhibitory influence on serotonergic neurons originating from the dorsal raphe . Brain Res279: 325-329
38.
Pallotta M , Segieth J , Whitton P S (1998) N-methyl-d-aspartate receptors regulate 5-HT release in the raphe nuclei and frontal cortex of freely moving rats: differential role of 5-HT1A autoreceptors . Brain Res783: 173-178
39.
Pan Z Z , Williams J T (1989) GABA- and glutamate-mediated synaptic potentials in rat dorsal raphe neurons in vitro . J Neurophysiol61: 719-726
40.
Partin K M , Patneau D K , Winters C A , Mayer M L , Buonanno A (1993) Selective modulation of desensitization at AMPA versus kainate receptors by cyclothiazide and concanavalin A . Neuron11: 1069-1082
41.
Patneau D K , Vyklicky L, Jr. , Mayer M L (1993) Hippocampal neurons exhibit cyclothiazide-sensitive rapidly desensitizing responses to kainate . J Neurosci13: 3496-3509
42.
Peyron C , Petit J M , Rampon C , Jouvet M , Luppi P H (1998) Forebrain afferents to the rat dorsal raphe nucleus demonstrated by retrograde and anterograde tracing methods . Neuroscience82: 443-468
43.
Pollard H , Charriaut-Marlangue C , Cantagrel S , Represa A , Robain O , Moreau J , Ben-Ari Y (1994) Kainate-induced apoptotic cell death in hippocampal neurons . Neuroscience63: 7-18
44.
Reisine T D , Soubrie P , Artaud F , Glowinski J (1982) Involvement of lateral habenula-dorsal raphe neurons in the differential regulation striatal and nigral serotonergic transmission in cats . J Neurosci2: 1062-1071
45.
Rueter, L E , Jacobs, B L (1996) A microdialysis examination of serotonin release in the rat forebrain induced by behavioral/environmental manipulations . Brain Res739: 57-69
46.
Romero L , Artigas F (1997) Preferential potentiation of the effects of serotonin uptake inhibitors by 5-HT1A receptor antagonists in the dorsal raphe pathway: role of somatodendritic autoreceptors . J Neurochem68: 2593-2603
47.
Rothman R B , Reid A A , Monn J A , Jacobson A E , Rice K C (1989) The psychotomimetic drug phencyclidine labels two high affinity binding sites in guinea pig brain: evidence for N-methyl-D-aspartate-coupled and dopamine reuptake carrierassociated phencyclidine binding sites . Mol Pharmacol36: 887-896
48.
Rutter J J , Gundlah C , Auerbach S B (1995) Systemic uptake inhibition decreases serotonin release via somatodendritic autoreceptor activation . Synapse20: 225-233
49.
Schwarcz R , Hokfelt T , Fuxe K , Jonson G , Goldstein M , Terenius L (1979) Ibotenic acid-induced neuronal degeneration: a morphological and neurochemical study . Exp Brain Res37: 199-216
50.
Sharp T , Bramwell S R , Clark D , Grahame-Smith D G (1989) In vivo measurements of brain extracellular 5-hydroxytryptamine using microdialysis: changes in relation to 5-hydroxytryptaminergic neuronal activity . J Neurochem53: 234-240
51.
Sharp T , Bramwell S R , Grahame-Smith D G (1990) Release of endogenous 5-hydroxytryptamine in rat ventral hippocampus evoked by electrical stimulation of the dorsal raphe nucleus as detected by microdialysis sensitivity to tetrodotoxin, calcium and calcium antagonists . Neuroscience39: 629-637
52.
Soloviev M M , Abutidze K , Mellor I , Streit P , Grishin E V , Usherwood P N , Barnard E A (1998) Plasticity of agonist binding sites in hetero-oligomers of the unitary glutamate receptor subunit XenU1 . J Neurochem71: 991-1001
53.
Sommer B , Burnashev N , Verdoorn T A , Keinanen K , Sakmann B , Seeburg P H (1992) A glutamate receptor channel with high affinity for domoate and kainate . EMBO J11: 1651-1656
54.
Sutton L C , Grahn R E , Wiertelak E P , Watkins L R , Maier S F (1997) Inescapable shock-induced potentiation of morphine analgesia in rats: involvement of opioid, GABAergic, and serotonergic mechanisms in the dorsal raphe nucleus . Behav Neurosci111: 816-824
55.
Tamminga C A (1998) Schizophrenia and glutamatergic transmission . Crit Rev Neurobiol12: 21-36
56.
Tao R , Auerbach S B (1994) Anesthetics block morphine-induced increases in serotonin release in rat CNS . Synapse18: 307-314
57.
Tao R , Auerbach S B (1996) Differential effect of NMDA on extracellular serotonin in rat midbrain raphe and forebrain sites . J Neurochem66: 1067-1075
58.
Tao R , Ma Z , Auerbach S B (1996) Differential regulation of 5-hydroxytryptamine release by GABAA and GABAB receptors in midbrain raphe nuclei and forebrain of rats . Br J Pharmacol119: 1375-1384
59.
Tao R , Ma Z , Auerbach S B (1997) Influence of AMPA/kainate receptors on extracellular 5-hydroxytryptamine in rat midbrain raphe and forebrain . Br J Pharmacol121: 1707-1715
60.
Tao R , Ma Z , Auerbach S B (1998) Alteration in regulation of serotonin release in rat dorsal raphe nucleus after prolonged exposure to morphine . J Pharmacol Exp Ther286: 481-488
61.
Tolle T R , Berthele A , Zieglgansberger W , Seeburg P H , Wisden W (1993) The differential expression of 16 NMDA and non-NMDA receptor subunits in the rat spinal cord and in periaqueductal gray . J Neurosci13: 5009-5028
62.
VanderMaelen C P , Matheson G K , Wilderman R C , Patterson L A (1986) Inhibition of dorsal raphe neurons by systemic and iontophoretic administration of buspirone, a nonbenzodiazepine anxiolytic drug . Eur J Pharmacol129: 123-130
63.
Wang Q P , Ochiai H , Nakai Y (1992) GABAergic innervation of serotonergic neurons in the dorsal raphe nucleus of the rat studies by electron microscopy double immunostaining . Brain Res Bull29: 943-948
64.
Wang R Y , Aghajanian G K (1977) Physiological evidence for habenula as major link between forebrain and midbrain raphe . Science197: 89-91
65.
Wang T , O'Connor W T , Ungerstedt U , French E D (1994) N-methyl-D-aspartic acid biphasically regulates the biochemical and electrophysiological response of A10 dopamine neurons in the ventral tegmental area: in vivo microdialysis and in vitro electrophysiological studies . Brain Res666: 255-262
66.
Westerink B H C , Santiago M , DeVries J B (1992) The release of dopamine from nerve terminals and dendrites of nigrostriatal neurons induced by excitatory amino acids in the conscious rat . Naunyn-Schmiedberg's Arch Pharmacol345: 523-529
67.
Wilkinson L O , Auerbach S B , Jacobs B L (1991) Extracellular serotonin levels change with behavioral state but not with pyrogen-induced hyperthermia . J Neurosci11: 2732-2741
68.
Willetts J , Balster R L , Leander J D (1990) The behavioral pharmacology of NMDA receptor antagonists [see comments] . Trends Pharmacol Sci11: 423-428
69.
Wong L A , Mayer M L (1993) Differential modulation by cyclothiazide and concanavalin A of desensitization at native alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionicacid and kainate-preferring glutamate receptors . Mol Pharmacol44: 504-510
70.
Yan Q S , Reith M E , Jobe P C , Dailey J W (1997) Dizocilpine (MK801) increases not only dopamine but also serotonin and norepinephrine transmissions in the nucleus accumbens as measured by microdialysis in freely moving rats . Brain Res765: 149-158
71.
Yang H , Peters J L , Michael A C (1998) Coupled effects of mass transfer and uptake kinetics on in vivo microdialysis of dopamine . J Neurochem71: 684-692
