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


CONCLUSIONS
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.
Department of Anesthesiology and Critical Care Medicine, Hokkaido University Graduate School of Medicine, Kita-15, Nishi-7, Kita-ku, Sapporo, 060-8638, Japan, ryokoit@pop.med.hokudai.ac.jp.
Ryoko Ito
RI
Kato
Kaori
K
Tachibana
Toshikazu
T
Hashimoto
Koichi
K
Takita
Yuji
Y
Morimoto
D000818:Animals; D056547:CA1 Region, Hippocampal / Q000187:drug effects*; D020927:Dexmedetomidine / Q000008:administration & dosage / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects; D006993:Hypnotics and Sedatives / Q000008:administration & dosage / Q000494:pharmacology*; D007274:Injections, Intraperitoneal; D017774:Long-Term Potentiation / Q000187:drug effects*; D008297:Male; D051381:Rats; D017208:Rats, Wistar
D006993:Hypnotics and Sedatives; D020927:Dexmedetomidine