Characterization of noradrenaline release in the locus coeruleus of freely moving awake rats by in vivo microdialysis.
BACKGROUND
The origin and regulation of noradrenaline (NA) in the locus coeruleus (LC) is unknown.


OBJECTIVE
The neurochemical features of NA overflow (nerve impulse dependence, neurotransmitter synthesis, vesicle storage, reuptake, alpha2-adrenoceptor-mediated regulation) were characterized in the LC.


METHODS
Brain microdialysis was performed in awake rats. Dialysates were analyzed for NA.


RESULTS
NA in the LC decreased via local infusion of Ca2+-free medium (-42+/-5%) or the sodium channel blocker tetrodotoxine (TTX) (-47+/-8%) but increased (333+/-40%) via KCl-induced depolarization. The tyrosine hydroxylase (TH) inhibitor alpha-methyl-p-tyrosine (250 mg kg(-1), i.p.) and the vesicle depletory drug reserpine (5 mg kg(-1), i.p.) decreased NA. Therefore, extracellular NA in the LC satisfies the criteria for an impulse flow-dependent vesicular exocytosis of neuronal origin. Local perfusion of the alpha2-adrenoceptor agonist clonidine (0.1-100 microM) decreased NA (E(max)=-79+/-5%) in the LC, whereas the opposite effect (E(max)=268+/-53%) was observed with the alpha2A-adrenoceptor antagonist BRL44408 (0.1-100 microM). This suggests a tonic modulation of NA release through local alpha2A-adrenoceptors. The selective NA reuptake inhibitor desipramine (DMI) (0.1-100 microM) administered into the LC increased NA in the LC (E(max)=223+/-40%) and simultaneously decreased NA in the cingulate cortex, confirming the modulation exerted by NA in the LC on firing activity of noradrenergic cells and on the subsequent NA release in noradrenergic terminals.


CONCLUSIONS
Synaptic processes underlying NA release in the LC are similar to those in noradrenergic terminal areas. NA in the LC could represent local somatodendritic release, but also the presence of neurotransmitter release from collateral axon terminals.
Fernández-Pastor
Begoña
B
Department of Pharmacology, University of Basque Country, 48940 Leioa, Bizkaia, Spain.
Mateo
Yolanda
Y
Gómez-Urquijo
Sonia
S
Javier Meana
J
J
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology; D002555:Cerebrospinal Fluid / Q000737:chemistry; D003000:Clonidine / Q000494:pharmacology; D015314:Dialysis Solutions / Q000008:administration & dosage / Q000737:chemistry; D045604:Extracellular Fluid / Q000737:chemistry / Q000187:drug effects; D007093:Imidazoles / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D054833:Isoindoles; D008125:Locus Coeruleus / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D017551:Microdialysis; D009043:Motor Activity / Q000502:physiology; D009638:Norepinephrine / Q000378:metabolism*; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012110:Reserpine / Q000494:pharmacology; D013572:Synaptic Vesicles / Q000187:drug effects / Q000378:metabolism; D013779:Tetrodotoxin / Q000008:administration & dosage / Q000494:pharmacology; D014851:Wakefulness / Q000502:physiology; D019805:alpha-Methyltyrosine / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D014150:Antipsychotic Agents; D015314:Dialysis Solutions; D007093:Imidazoles; D007211:Indoles; D054833:Isoindoles; D013779:Tetrodotoxin; D019805:alpha-Methyltyrosine; D011189:Potassium Chloride; D012110:Reserpine; D003000:Clonidine; D009638:Norepinephrine; C072125:BRL 44408
Naunyn Schmiedebergs Arch Pharmacol. 1994 Oct;350(4):339-45
7845470
J Neurochem. 1995 Jul;65(1):192-200
7790860
Neuroscience. 1995 Mar;65(1):119-60
7753394
Brain Res. 1997 Jul 18;763(1):56-62
9272828
Physiol Rev. 1983 Jul;63(3):844-914
6308694
Neuroreport. 1999 May 14;10(7):1583-7
10380985
Neuroscience. 1990;39(3):629-37
2097517
Acta Physiol Scand Suppl. 1971;367:1-48
4109331
Ann Neurol. 1992 Nov;32(5):667-76
1449247
J Neurochem. 1991 Sep;57(3):738-47
1677674
J Neurochem. 1991 Mar;56(3):961-7
1993900
Exp Brain Res. 1979 Sep;37(1):139-48
488212
Brain Res Brain Res Rev. 2004 Apr;45(1):38-78
15063099
Brain Res. 1986 May 28;374(2):299-305
3719339
Prog Neurobiol. 1998 Oct;56(2):237-67
9760703
J Pharmacol Exp Ther. 1992 Jan;260(1):427-36
1731049
J Neurochem. 1986 Jun;46(6):1794-801
2871129
Neuroscience. 1980;5(1):21-40
6988734
Brain Res. 1977 Nov 18;136(3):570-7
922502
J Neurosci. 1997 Mar 1;17(5):1710-9
9030630
Psychopharmacology (Berl). 1999 Oct;146(3):335-8
10541735
J Neurochem. 2000 Jun;74(6):2350-8
10820195
J Neurosci. 1991 Jul;11(7):2209-16
1712381
Brain Res Brain Res Rev. 2002 Sep;39(2-3):154-80
12423765
Nature. 1981 Feb 12;289(5798):537-42
6258083
Neurosci Lett. 1990 Nov 13;119(2):233-6
2280900
J Neurochem. 1998 Aug;71(2):790-8
9681471
Trends Pharmacol Sci. 1996 Oct;17(10):356-63
8979770
J Psychopharmacol. 1999 Dec;13(4):379-84
10667614
Brain Res Bull. 1982 Feb;8(2):123-9
7066704
Science. 1978 Dec 8;202(4372):1089-91
213833
Naunyn Schmiedebergs Arch Pharmacol. 1991 Mar;343(3):237-44
1714040
Brain Res. 1994 Jan 21;634(2):275-82
8131077
Neurosci Biobehav Rev. 2004 Jul;28(4):415-31
15289006
J Neurochem. 1988 Sep;51(3):683-7
3411321
Eur J Pharmacol. 2002 May 10;442(3):225-9
12065075
Biol Psychiatry. 1999 Nov 1;46(9):1219-33
10560027
Neuroscience. 1988 Dec;27(3):897-904
3252176
Eur J Pharmacol. 1999 Jan 29;366(1):35-9
10064149
Brain Res. 1976 Jun 25;110(1):39-56
776360
Br J Pharmacol. 1995 Apr;114(8):1717-23
7599940
Brain Res. 1994 May 9;645(1-2):135-42
8062076
Synapse. 1995 Sep;21(1):85-92
8525466
Acta Physiol Scand Suppl. 1964;:SUPPL 232:1-55
14229500
Brain Res. 1999 Mar 27;823(1-2):42-8
10095010
Br J Pharmacol. 1999 Oct;128(3):659-66
10516646
Eur J Pharmacol. 1999 Aug 20;379(1):53-7
10499371
Annu Rev Neurosci. 1979;2:113-68
231924
J Neurochem. 1983 Dec;41(6):1769-73
6196446
Br J Pharmacol. 1998 Nov;125(6):1361-7
9863668
J Neurochem. 1991 May;56(5):1741-6
1672885
Neuropharmacology. 1994 Mar-Apr;33(3-4):411-21
7984279
Brain Res. 1989 Oct 16;499(2):281-90
2478259
Brain Res. 1991 Aug 23;557(1-2):5-12
1720998
Br J Pharmacol. 1993 Jul;109(3):655-60
8102934
J Neural Transm (Vienna). 1996;103(1-2):173-90
9026372
Brain Res. 1993 Mar 5;605(1):128-38
8467382
J Neurochem. 1993 May;60(5):1673-81
7682600
J Neurochem. 1993 Aug;61(2):594-601
7687655
Prog Brain Res. 1991;88:1-642
1687615
J Pharmacol Exp Ther. 1987 May;241(2):642-9
3033221
Brain Res. 2001 Jul 6;906(1-2):38-45
11430860
Brain Res. 1976 Aug 13;112(2):413-9
8191
Brain Res Brain Res Rev. 2003 Apr;42(1):33-84
12668290