Abstract
Research interest in the field of interactions between brain neurons that utilize different neurotransmitters is growing rapidly. To obtain evidence for this transmitter-mediated cross-talk between neurons, investigation of transmitter release in distinct brain areas under in vivo conditions is particularly useful. The studies described in the present review were carried out using the push–pull superfusion technique, which makes it possible to superfuse distinct brain areas and to determine the release of endogenous neurotransmitters in the superfusate. The brain areas investigated were the posterior hypothalamus, the basolateral nucleus of the amygdala and the locus coeruleus. Using this technique we have found that alterations in the extracellular concentration of serotonin may contribute to the modulation of the activity of locus coeruleus neurons in response to chemosensory stimuli. We have also observed an exaggerated stress response of glutamatergic neurons in the amygdala of spontaneously hypertensive as compared with Wistar-Kyoto rats, which might be of significance for the strain differences in the cardiovascular and behavioral responses to stress. In sinaortic denervated rats, blood pressure lability was greatly enhanced and accompanied by increased basal release of glutamate in the locus coeruleus. Finally, behavioral studies revealed that inescapable electric foot shock enhances significantly the release of several amino acids in the locus coeruleus. Given the success of the push–pull experiments, the same technique can be used in future behavioral studies, in order to investigate the release of neurotransmitters during behavioral and cognitive performance. Similar investigations in bilateral aortic denervated animals are also important in order to define whether the emotional and cognitive disturbances are induced by inhibition of blood pressure stimuli to the brain or by hypertension and increased pressure lability.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Similar content being viewed by others
References
Myhrer T (2003) Neurotransmitter systems involved in learning and memory in the rat: a meta-analysis based on studies of four behavioral tasks. Brain Res Brain Res Rev 41:268–287
Chandler DJ (2016) Evidence for a specialized role of the locus coeruleus noradrenergic system in cortical circuitries and behavioral operations. Brain Res 1641:197
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
Singewald N, Kaehler ST, Hemeida R, Philippu A (1998) Influence of excitatory amino acids on basal and sensory stimuli-induced release of 5-HT in the locus coeruleus. Br J Pharmacol 123:746–752
Singewald N, Kouvelas D, Kaehler ST, Sinner C, Philippu A (2000) Peripheral chemoreceptor activation enhances 5-hydroxytryptamine release in the locus coeruleus of conscious rats. Neurosci Lett 289:17–20
Singewald N, Guo L, Philippu A (1993) Release of endogenous GABA in the posterior hypothalamus of the conscious rat; effects of drugs and experimentally induced blood pressure changes. Naunyn Schmiedebergs Arch Pharmacol 347:402–406
Singewald N, Guo LJ, Schneider C, Kaehler S, Philippu A (1995) Serotonin outflow in the hypothalamus of conscious rats: origin and possible involvement in cardiovascular control. Eur J Pharmacol 294:787–793
Singewald N, Schneider C, Philippu A (1994) Disturbances in blood pressure homeostasis modify GABA release in the locus coeruleus. Neuroreport 5:1709–1712
Philippu A (2001) In vivo neurotransmitter release in the locus coeruleus--effects of hyperforin, inescapable shock and fear. Pharmacopsychiatry 34(Suppl 1):S111–S115
Singewald N, Guo LJ, Philippu A (1993) Taurine release in the hypothalamus is altered by blood pressure changes and neuroactive drugs. Eur J Pharmacol 240:21–27
Kimura S, Ohshige Y, Lin L, Okumura T, Yanaihara C, Yanaihara N, Shiotani Y (1994) Localization of pituitary adenylate cyclase-activating polypeptide (PACAP) in the hypothalamus-pituitary system in rats: light and electron microscopic immunocytochemical studies. J Neuroendocrinol 6:503–507
Voisin DL, Chapman C, Poulain DA, Herbison AE (1994) Extracellular GABA concentrations in rat supraoptic nucleus during lactation and following haemodynamic changes: an in vivo microdialysis study. Neuroscience 63:547–558
Philippu A (1988) Regulation of blood pressure by central neurotransmitters and neuropeptides. Rev Physiol Biochem Pharmacol 111:1–115
Wible JH Jr, Luft FC, DiMicco JA (1988) Hypothalamic GABA suppresses sympathetic outflow to the cardiovascular system. Am J Physiol 254:R680–R687
Singewald N, Philippu A (1996) Involvement of biogenic amines and amino acids in the central regulation of cardiovascular homeostasis. Trends Pharmacol Sci 17:356–363
Singewald N, Pfitscher A, Philippu A (1992) Effects of gamma-vinyl GABA (Vigabatrin) on blood pressure and body weight of hypertensive and normotensive rats. Naunyn Schmiedebergs Arch Pharmacol 345:181–186
Shonis CA, Peano CA, Dillon GH, Waldrop TG (1993) Cardiovascular responses to blockade of GABA synthesis in the hypothalamus of the spontaneously hypertensive rat. Brain Res Bull 31:493–499
Franchini KG, Krieger EM (1993) Cardiovascular responses of conscious rats to carotid body chemoreceptor stimulation by intravenous KCN. J Auton Nerv Syst 42:63–69
Haibara AS, Colombari E, Chianca DA Jr, Bonagamba LG, Machado BH (1995) NMDA receptors in NTS are involved in bradycardic but not in pressor response of chemoreflex. Am J Physiol 269:1421–1427
Hayward LF, Johnson AK, Felder RB (1999) Arterial chemoreflex in conscious normotensive and hypertensive adult rats. Am J Physiol 276:1215–1222
Vasquez EC, Meyrelles SS, Mauad H, Cabral AM (1997) Neural reflex regulation of arterial pressure in pathophysiological conditions: interplay among the baroreflex, the cardiopulmonary reflexes and the chemoreflex. Braz J Med Biol Res 30:521–532
Singewald N, Kouvelas D, Chen F, Philippu A (1997) The release of inhibitory amino acids in the hypothalamus is tonically modified by impulses from aortic baroreceptors as a consequence of blood pressure fluctuations. Naunyn Schmiedebergs Arch Pharmacol 356:348–355
Singewald N, Kouvelas D, Mostafa A, Sinner C, Philippu A (2000) Release of glutamate and GABA in the amygdala of conscious rats by acute stress and baroreceptor activation: differences between SHR and WKY rats. Brain Res 864:138–141
File SE, Zangrossi H Jr, Sanders FL, Mabbutt PS (1994) Raised corticosterone in the rat after exposure to the elevated plus-maze. Psychopharmacology (Berl) 113:543–546
Pellow S, Chopin P, File SE, Briley M (1985) Validation of open:closed arm entries in an elevated plus-maze as a measure of anxiety in the rat. J Neurosci Methods 14:149–167
Bannerman DM, Rawlins JN, McHugh SB, Deacon RM, Yee BK, Bast T, Zhang WN, Pothuizen HH, Feldon J (2004) Regional dissociations within the hippocampus--memory and anxiety. Neurosci Biobehav Rev 28:273–283
Walf AA, Frye CA (2007) The use of the elevated plus maze as an assay of anxiety-related behavior in rodents. Nat Protoc 2:322–328
Kouvelas D, Pourzitaki C, Papazisis G, Dagklis T, Dimou K, Kraus MM (2008) Nandrolone abuse decreases anxiety and impairs memory in rats via central androgenic receptors. Int J Neuropsychopharmacol 11:925–934
Koks S, Bourin M, Voikar V, Soosaar A, Vasar E (1999) Role of CCK in anti-exploratory action of paroxetine, 5-HT reuptake inhibitor. Int J Neuropsychopharmacol 2:9–16
Cohen H, Maayan R, Touati-Werner D, Kaplan Z, Matar A, Loewenthal U, Kozlovsky N, Weizman R (2007) Decreased circulatory levels of neuroactive steroids in behaviourally more extremely affected rats subsequent to exposure to a potentially traumatic experience. Int J Neuropsychopharmacol 10:203–209
Holloway WR Jr, Thor DH (1988) Social memory deficits in adult male rats exposed to cadmium in infancy. Neurotoxicol Teratol 10:193–197
Sawyer TF, Hengehold AK, Perez WA (1984) Chemosensory and hormonal mediation of social memory in male rats. Behav Neurosci 98:908–913
Dantzer R, Bluthe RM, Koob GF, Le Moal M (1987) Modulation of social memory in male rats by neurohypophyseal peptides. Psychopharmacology (Berl) 91:363–368
Prediger RD, Takahashi RN (2003) Ethanol improves short-term social memory in rats. Involvement of opioid and muscarinic receptors. Eur J Pharmacol 462:115–123
Engelmann M, Wotjak CT, Landgraf R (1995) Social discrimination procedure: an alternative method to investigate juvenile recognition abilities in rats. Physiol Behav 58:315–321
Popik P, van Ree JM (1998) Neurohypophyseal peptides and social recognition in rats. Prog Brain Res 119:415–436
Kaehler ST, Sinner C, Kouvelas D, Philippu A (2000) Effects of inescapable shock and conditioned fear on the release of excitatory and inhibitory amino acids in the locus coeruleus. Naunyn Schmiedebergs Arch Pharmacol 361:193–199
Krieger EM (1964) Neurogenic hypertension in the rat. Circ Res 15:511–521
Nowak SJ (1940) Chronic hypertension produced by carotid sinus and aortic-depressor nerve section. Ann Surg 111:102–111
Kouvelas D, Singewald N, Kaehler ST, Philippu A (2006) Sinoaortic denervation abolishes blood pressure-induced GABA release in the locus coeruleus of conscious rats. Neurosci Lett 393:194–199
Abdel-Rahman AA (1992) Aortic baroreceptors exert a tonically active restraining influence on centrally mediated depressor responses. J Cardiovasc Pharmacol 19:233–245
Paxinos G, Watson C (1996) The rat brain in stereotaxic coordinates. Academic, San Diego, CA
Kouvelas D, Pourzitaki C, Papazisis G, Tsilkos K, Chourdakis M, Kraus MM (2009) Chronic aortic denervation decreases anxiety and impairs social memory in rats. Life Sci 85:602–608
Kouvelas D, Amaniti E, Pourzitaki C, Kapoukranidou D, Thomareis O, Papazisis G, Vasilakos D (2009) Baroreceptors discharge due to bilateral aortic denervation evokes acute neuronal damage in rat brain. Brain Res Bull 79:142–146
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2017 Springer Science+Business Media New York
About this protocol
Cite this protocol
Kouvelas, D., Papazisis, G., Pourzitaki, C., Goulas, A. (2017). Involvement of Neurotransmitters in Behavior and Blood Pressure Control. In: Philippu, A. (eds) In Vivo Neuropharmacology and Neurophysiology. Neuromethods, vol 121. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-6490-1_13
Download citation
DOI: https://doi.org/10.1007/978-1-4939-6490-1_13
Published:
Publisher Name: Humana Press, New York, NY
Print ISBN: 978-1-4939-6488-8
Online ISBN: 978-1-4939-6490-1
eBook Packages: Springer Protocols