Skip to main content
Top
Published in: Journal of Anesthesia 6/2014

01-12-2014 | Original Article

Dexmedetomidine suppresses long-term potentiation in the hippocampal CA1 field of anesthetized rats

Authors: Ryoko Ito Kato, Kaori Tachibana, Toshikazu Hashimoto, Koichi Takita, Yuji Morimoto

Published in: Journal of Anesthesia | Issue 6/2014

Login to get access

Abstract

Purpose

The aim of this study was to evaluate the effect of dexmedetomidine (DEX) on hippocampal synaptic activity in vivo.

Methods

The adult rats used for this study received a intraperitoneal bolus injection of 3, 10, 30, or 100 μg/kg of DEX or an equivalent volume of saline. Electrophysiological recording of the hippocampal CA1 region was initiated 20 min after drug administration. The results are expressed as the percentages of the population spike amplitude measured just before high-frequency stimulation (HFS). The electrophysiological data were analyzed with an area under the curve (AUC) of 10–60 min after HFS. Moreover, to investigate the sedative dose of DEX in rats, we recorded the duration of loss of spontaneous movement after the administration of each dose of DEX.

Results

Intraperitoneal administration of DEX at doses of 30 and 100 μg/kg induced a range of sedative effects. The AUC measurements were significantly lower in the 30 and 100 μg/kg groups than in those injected with vehicle (vehicle: 8.81 ± 0.49, n = 7; DEX 30 µg/kg: 6.02 ± 0.99, n = 6; DEX 100 µg/kg: 5.10 ± 0.43, n = 5; P < 0.05).

Conclusion

The results of our in vivo study reveal that sedative doses of DEX impaired the induction of hippocampal long-term potentiation (LTP). These findings may signify a causal link between DEX-induced sedative action and hippocampal LTP suppression, providing a better understanding of the mechanisms underlying the DEX-induced sedative and/or amnestic effect.
Literature
1.
go back to reference Buerkle H, Yaksh TL. Pharmacological evidence for different alpha 2-adrenergic receptor sites mediating analgesia and sedation in the rat. Br J Anaesth. 1998;81(2):208–15.PubMedCrossRef Buerkle H, Yaksh TL. Pharmacological evidence for different alpha 2-adrenergic receptor sites mediating analgesia and sedation in the rat. Br J Anaesth. 1998;81(2):208–15.PubMedCrossRef
2.
go back to reference Martin E, Ramsay G, Mantz J, Sum-Ping ST. The role of the alpha2-adrenoceptor agonist dexmedetomidine in postsurgical sedation in the intensive care unit. J Intensive Care Med. 2003;18(1):29–41.PubMedCrossRef Martin E, Ramsay G, Mantz J, Sum-Ping ST. The role of the alpha2-adrenoceptor agonist dexmedetomidine in postsurgical sedation in the intensive care unit. J Intensive Care Med. 2003;18(1):29–41.PubMedCrossRef
3.
go back to reference Ramsay MA, Luterman DL. Dexmedetomidine as a total intravenous anesthetic agent. Anesthesiology. 2004;101(3):787–90.PubMedCrossRef Ramsay MA, Luterman DL. Dexmedetomidine as a total intravenous anesthetic agent. Anesthesiology. 2004;101(3):787–90.PubMedCrossRef
4.
go back to reference Ebert TJ, Hall JE, Barney JA, Uhrich TD, Colinco MD. The effects of increasing plasma concentrations of dexmedetomidine in humans. Anesthesiology. 2000;93(2):382–94.PubMedCrossRef Ebert TJ, Hall JE, Barney JA, Uhrich TD, Colinco MD. The effects of increasing plasma concentrations of dexmedetomidine in humans. Anesthesiology. 2000;93(2):382–94.PubMedCrossRef
5.
go back to reference Pryor KO, Reinsel RA, Mehta M, Li Y, Wixted JT, Veselis RA. Visual P2–N2 complex and arousal at the time of encoding predict the time domain characteristics of amnesia for multiple intravenous anesthetic drugs in humans. Anesthesiology. 2010;113(2):313–26.PubMedCentralPubMedCrossRef Pryor KO, Reinsel RA, Mehta M, Li Y, Wixted JT, Veselis RA. Visual P2–N2 complex and arousal at the time of encoding predict the time domain characteristics of amnesia for multiple intravenous anesthetic drugs in humans. Anesthesiology. 2010;113(2):313–26.PubMedCentralPubMedCrossRef
6.
go back to reference Hayama HR, Drumheller KM, Mastromonaco M, Reist C, Cahill LF, Alkire MT. Event-related functional magnetic resonance imaging of a low dose of dexmedetomidine that impairs long-term memory. Anesthesiology. 2012;117(5):981–95.PubMedCentralPubMedCrossRef Hayama HR, Drumheller KM, Mastromonaco M, Reist C, Cahill LF, Alkire MT. Event-related functional magnetic resonance imaging of a low dose of dexmedetomidine that impairs long-term memory. Anesthesiology. 2012;117(5):981–95.PubMedCentralPubMedCrossRef
7.
go back to reference Bliss TV, Collingridge GL. A synaptic model of memory: long-term potentiation in the hippocampus. Nature. 1993;361(6407):31–9.PubMedCrossRef Bliss TV, Collingridge GL. A synaptic model of memory: long-term potentiation in the hippocampus. Nature. 1993;361(6407):31–9.PubMedCrossRef
8.
go back to reference Takamatsu I, Iwase A, Ozaki M, Kazama T, Wada K, Sekiguchi M. Dexmedetomidine reduces long-term potentiation in mouse hippocampus. Anesthesiology. 2008;108(1):94–102.PubMedCrossRef Takamatsu I, Iwase A, Ozaki M, Kazama T, Wada K, Sekiguchi M. Dexmedetomidine reduces long-term potentiation in mouse hippocampus. Anesthesiology. 2008;108(1):94–102.PubMedCrossRef
9.
go back to reference Tachibana K, Hashimoto T, Kato R, Tsuruga K, Ito R, Morimoto Y. Long-lasting effects of neonatal pentobarbital administration on spatial learning and hippocampal synaptic plasticity. Brain Res. 2011;1388:69–76.PubMedCrossRef Tachibana K, Hashimoto T, Kato R, Tsuruga K, Ito R, Morimoto Y. Long-lasting effects of neonatal pentobarbital administration on spatial learning and hippocampal synaptic plasticity. Brain Res. 2011;1388:69–76.PubMedCrossRef
10.
go back to reference Tachibana K, Takita K, Hashimoto T, Matsumoto M, Yoshioka M, Morimoto Y. Isoflurane bidirectionally modulates the paired-pulse responses in the rat hippocampal CA1 field in vivo. Anesth Analg. 2007;105(4):1006–11.PubMedCrossRef Tachibana K, Takita K, Hashimoto T, Matsumoto M, Yoshioka M, Morimoto Y. Isoflurane bidirectionally modulates the paired-pulse responses in the rat hippocampal CA1 field in vivo. Anesth Analg. 2007;105(4):1006–11.PubMedCrossRef
11.
go back to reference Virtanen R, Savola JM, Saano V, Nyman L. Characterization of the selectivity, specificity and potency of medetomidine as an alpha 2-adrenoceptor agonist. Eur J Pharmacol. 1988;150(1–2):9–14.PubMedCrossRef Virtanen R, Savola JM, Saano V, Nyman L. Characterization of the selectivity, specificity and potency of medetomidine as an alpha 2-adrenoceptor agonist. Eur J Pharmacol. 1988;150(1–2):9–14.PubMedCrossRef
12.
go back to reference Tachibana K, Hashimoto T, Kato R, Uchida Y, Ito R, Takita K, Morimoto Y. Neonatal administration with dexmedetomidine does not impair the rat hippocampal synaptic plasticity later in adulthood. Paediatr Anaesth. 2012;22(7):713–9.PubMedCrossRef Tachibana K, Hashimoto T, Kato R, Uchida Y, Ito R, Takita K, Morimoto Y. Neonatal administration with dexmedetomidine does not impair the rat hippocampal synaptic plasticity later in adulthood. Paediatr Anaesth. 2012;22(7):713–9.PubMedCrossRef
13.
go back to reference Niittykoski M, Haapalinna A, Sirvio J. Diminution of N-methyl-d-aspartate-induced perturbation of neurotransmission by dexmedetomidine in the CA1 field of rat hippocampus in vitro. Neurosci Lett. 2000;281(2–3):95–8.PubMedCrossRef Niittykoski M, Haapalinna A, Sirvio J. Diminution of N-methyl-d-aspartate-induced perturbation of neurotransmission by dexmedetomidine in the CA1 field of rat hippocampus in vitro. Neurosci Lett. 2000;281(2–3):95–8.PubMedCrossRef
14.
go back to reference Kamibayashi T, Maze M. Clinical uses of alpha2-adrenergic agonists. Anesthesiology. 2000;93(5):1345–9.PubMedCrossRef Kamibayashi T, Maze M. Clinical uses of alpha2-adrenergic agonists. Anesthesiology. 2000;93(5):1345–9.PubMedCrossRef
15.
go back to reference Dawson C, Ma D, Chow A, Maze M. Dexmedetomidine enhances analgesic action of nitrous oxide: mechanisms of action. Anesthesiology. 2004;100(4):894–904.PubMedCrossRef Dawson C, Ma D, Chow A, Maze M. Dexmedetomidine enhances analgesic action of nitrous oxide: mechanisms of action. Anesthesiology. 2004;100(4):894–904.PubMedCrossRef
16.
go back to reference Bol CJ, Vogelaar JP, Mandema JW. Anesthetic profile of dexmedetomidine identified by stimulus-response and continuous measurements in rats. J Pharmacol Exp Ther. 1999;291(1):153–60.PubMed Bol CJ, Vogelaar JP, Mandema JW. Anesthetic profile of dexmedetomidine identified by stimulus-response and continuous measurements in rats. J Pharmacol Exp Ther. 1999;291(1):153–60.PubMed
17.
go back to reference Blaise JH, Bronzino JD. Effects of stimulus frequency and age on bidirectional synaptic plasticity in the dentate gyrus of freely moving rats. Exp Neurol. 2003;182(2):497–506.PubMedCrossRef Blaise JH, Bronzino JD. Effects of stimulus frequency and age on bidirectional synaptic plasticity in the dentate gyrus of freely moving rats. Exp Neurol. 2003;182(2):497–506.PubMedCrossRef
18.
go back to reference Bordi F, Reggiani A, Conquet F. Regulation of synaptic plasticity by mGluR1 studied in vivo in mGluR1 mutant mice. Brain Res. 1997;761(1):121–6.PubMedCrossRef Bordi F, Reggiani A, Conquet F. Regulation of synaptic plasticity by mGluR1 studied in vivo in mGluR1 mutant mice. Brain Res. 1997;761(1):121–6.PubMedCrossRef
Metadata
Title
Dexmedetomidine suppresses long-term potentiation in the hippocampal CA1 field of anesthetized rats
Authors
Ryoko Ito Kato
Kaori Tachibana
Toshikazu Hashimoto
Koichi Takita
Yuji Morimoto
Publication date
01-12-2014
Publisher
Springer Japan
Published in
Journal of Anesthesia / Issue 6/2014
Print ISSN: 0913-8668
Electronic ISSN: 1438-8359
DOI
https://doi.org/10.1007/s00540-014-1853-3

Other articles of this Issue 6/2014

Journal of Anesthesia 6/2014 Go to the issue