Abstract
To investigate the release of endogenous dopamine, noradrenaline and adrenaline in the locus coeruleus, this brain area was superfused with artificial cerebrospinal fluid (CSF) through push-pull cannulae and the release of catecholamines was determined in the superfusate radioenzymatically.
Collection of superfusates in time periods of 10 min revealed that release rates of the three catecholamines fluctuated, thus pointing to the existence of ultradian rhythms with following mean periods (minutes per cycle): noradrenaline 52±4, dopamine 37±2, adrenaline 36±2. The rhythm frequency of noradrenaline was significantly lower than the frequencies of dopamine and adrenaline.
When the locus coeruleus was superfused with neuroactive drugs, superfusates were collected in time periods of 3 min. Superfusion with tetrodotoxin (1 μmol 1−1) for 12 min elicited a prompt and sustained decrease (−70%) in the release rates of dopamine and adrenaline. The release rate of noradrenaline was also reduced, although to a lesser extent (−40%). Superfusion with veratridine (50 μmol 1−1) led to an immediate and very pronounced enhancement in the release rates of dopamine, noradrenaline and adrenaline. The veratridine-induced increase in catecholamine outflow was decreased strongly by simultaneous superfusion with tetrodotoxin.
The findings suggest that the release of endogenous catecholamines in the locus coeruleus fluctuates according to ultradian rhythms. Changes in the release on superfusion with veratridine and tetrodotoxin demonstrate the neuronal origin of the three catecholamines. The observed differences in the release characteristics between noradrenaline on the one hand and dopamine and adrenaline on the other might indicate that noradrenaline is partly released from somatodendritic sites of the noradrenergic cell bodies in the locus coeruleus.
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References
Abercrombie ED, Keller RW, Zigmond MJ (1988) Characterization of hippocampal norepinephrine release as measured by microdialysis perfusion: pharmacological and behavioral studies. Neuroscience 27:897–904
Berman AL (1968) The brainstem of the cat. A cytoarchitectonic atlas with stereotaxic coordinates. The University of Wisconsin Press, Madison
Bhaskaran D, Freed CR (1988) Changes in neurotransmitter turnover in locus coeruleus produced by changes in arterial blood pressure. Brain Res Bull 21:191–199
Buda M, De Simoni MG, Gonon F, Pujol JF (1983) Catecholamine metabolism in the rat locus coeruleus as studied by in vivo differential pulse voltammetry: I. Nature and origin of contributors to the oxidation current at +0.1 V. Brain Res 273:197–206
Buda M, Gonon F (1987) Study of brain noradrenergic neurons by use of in vivo voltammetry. In: Justice JB Jr (ed) Voltammetry in the neurosciences. Humana Press, Clifton, NJ, pp 239–272
Clement HW, Gemsa D, Weseman W (1992) Serotonin-norepinephrine interactions: a voltammetric study on the effect of serotonin receptor stimulation followed in the N. raphe dorsalis and the locus coeruleus of the rat. J Neural Transm 88:11–23
Daan S, Aschoff J (1981) Short term rhythms in activity. In: Aschoff J (ed) Handbook of behavioural neurobiology, vol 4. Biological rhythms. Plenum Press, New York, pp 491–498
Dahlström A, Fuxe K (1964) Evidence for the existence of monoamine-containing neurons in the central nervous system. I. Demonstration of monoamines in the cell bodies of brainstem neurons. Acta Physiol Scand [Suppl 232] 62:1–55
Dietl H, Prast H, Philippu A (1993) Pulsatile release of catecholamines in the hypothalamus of conscious rats. Naunyn-Schmiedeberg's Arch Pharmacol 347:28–33
Fairbrother IS, Arbuthnott GW, Kelly JS, Butcher SP (1990) In vivo mechanisms underlying dopamine release from rat nigrostriatal terminals: I. Studies using veratridine and ouabain. J Neurochem 54:1834–1843
Foote SL, Bloom FE, Aston-Jones G (1983) The nucleus locus coeruleus: new evidence of anatomical and physiological specifity. Physiol Rev 69:844–914
Groves PM, Wilson CJ (1980) Monoaminergic presynaptic axons and dendrites in rat locus coeruleus seen in reconstructions of serial sections. J Comp Neurol 193:853–862
Hong M, Milne B, Loomis CW Jhamandas K (1992) In vivo catechol activity in the rat locus coeruleus following different nociceptive stimuli and naloxone. Can J Physiol Pharmacol 70:1082–1089
Keefe KA, Zigmond MJ, Abercrombie ED (1992) Extracellular dopamine in striatum: influence of nerve impulse activity in medial forebrain bundle and local glutamatergic input. Neuroscience 47:325–332
Klausmair A, Singewald N, Philippu A (1991) Release of endogenous catecholamines in two different regions of the nucleus of the solitary tract as influenced by carotid occlusion. Naunyn-Schmiedeberg's Arch Pharmacol 343:155–160
Koda LY, Aston-Jones G, Bloom FE (1980) Small granular vesicles in the locus coeruleus may indicate dendritic release of norepinephrine. Soc Neurosci Abstr 6:446
Lanzinger I, Kobilansky C, Philippu A (1989) Pattern of catecholamine release in the nucleus tractus solitarii of the cat. Naunyn-Schmiedeberg's Arch Pharmacol 339:298–301
Miachon S, Berod A, Leger L, Chat M, Hartman B, Pujol JF (1984) Identification of catecholamine cell bodies in the pons and pons-mesenphalon junction of the cat brain, using tyrosine hydroxylase and dopamine-β-hydroxylase immunohistochemistry. Brain Res 305:369–374
Philippu A (1984) Use of push-pull cannulae to determine the release of endogenous neurotransmitters in distinct brain areas of anaesthetized and freely moving animals. In: Marsden CA (ed) Measurement of neurotransmitter release in vivo. John Wiley, Chichester, pp 3–73
Philippu A (1988) Regulation of blood pressure by central neurotransmitters and neuropeptides. Rev Physiol Biochem Pharmacol 111: 1–115
Philippu A, Dietl H, Sinha JN (1979) In vivo release of endogenous catecholamines in the hypothalamus. Naunyn-Schmiedeberg's Arch Pharmacol 308:137–142
Quintin L, Hilaire G, Pujol JF (1986) Variations in 3,4-dihydroxypecnylacetic acid concentration are correlated to single cell firing changes in the rat locus coeruleus. Neuroscience 18:889–899
Robinson RL, Dietl H, Bald M, Kraus A, Philippu A (1983) Effects of short-lasting and long-lasting blood pressure changes on the release of endogenous catecholamines in the hypothalamus of the conscious, freely moving rabbit. Naunyn-Schmiedeberg's Arch Pharmacol 322:203–209
Sakai K (1991) Physiological properties and afferent connections of the locus coeruleus and adjacent tegmental neurons involved in the generation of paradoxical sleep in the cat. In: Barnes CD, Pompeiano P (ed) Neurobiology of the Locus Coeruleus. Elsevier, Amsterdam, pp 31–45
Sakai K, Yoshimoto Y, Luppi PH, El Mansari M, Salvert D, Jouvet M (1990) Lower brainstem afferents to the cat posterior hypothalamus double-labelling study. Brain Res Bull 24:437–455
Santiago M, Westerink BHC (1992) Simultaneous recording of the release of nigral and striatal dopamine in the awake rat. Neurochem Int [Suppl] 20:1075–1105
Shimizu N, Katoh Y, Hida T, Satoh K (1979) The fine structural organization of the locus coeruleus in the rat with reference to noradrenaline contents. Exp Brain Res 37:139–148
Singewald N, Philippu A (1993) Catecholamine release in the locus coeruleus is modified by experimentally induced changes in haemodynamics. Naunyn-Schmiedeberg's Arch Pharmacol 347:21–27
Singewald N, Schneider C, Philippu A (1993) Effects of blood pressure changes on the catecholamine release in the locus coeruleus of cats anaesthetized with pentobarbital or chloralose. Naunyn-Schmiedeberg's Arch Pharmacol 348:242–248
Tallarida RJ, Murray RB (1987) Manual of pharmacologic calculations with computer programs. Springer, Berlin Heidelberg New York, pp 75–77
Thrivikraman KV, Carlson DE, Gann DS (1988a) Locus coeruleus monoaminergic activity and plasma corticotropin after hemorrhage in cats. Am J Physiol 254:8289–8295
Thrivikraman KV, Carlson DE, Gann DS (1988b) Noradrenergic turnover increases in locus coeruleus after hemorrhage in cats. Am J Physiol 254:R296–R301
Ulbricht W (1969) The effect of veratridine on excitable membranes of nerve and muscle. Rev Physiol Biochem Pharmac 61:18–71
Van Cauter E (1981) Quantitative methods for the analysis of circadian and episodic hormone fluctuations. In: Van Cauter E, Copinschi G (eds) Circadian and episodic variations. Nyhoff, The Hague, pp 1–25
Wiklund L, Leger L, Persson M (1981) Monoamine cell distribution in the cat brainstem. A fluorescence histochemical study with quantification of indolaminergic and locus coeruleus cell groups. J Comp Neurol 203:613–647
Williams JT, North RA, Shefner SA, Noshi S, Egan TM (1984) Membrane properties of rat locus coeruleus neurons. Neuroscience 13:137–156
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This work was supported by the Fonds zur Förderung der wissenschaftlichen Forschung
Correspondence to: N. Singewald at the above address
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Singewald, N., Schneider, C., Pfitscher, A. et al. In vivo release of catecholamines in the locus coeruleus. Naunyn-Schmiedeberg's Arch Pharmacol 350, 339–345 (1994). https://doi.org/10.1007/BF00178948
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DOI: https://doi.org/10.1007/BF00178948