Open Access(R)‐alpha‐methylhistamine Suppresses Inhibitory Neurotransmission in Hippocampal CA 1 Pyramidal Neurons Counteracting Propofol‐Induced Amnesia in Rats
Author(s) -
Li WeiWei,
Cheng LongZhen,
Zou Zui,
Tian MouLi,
Zhang Hao,
Raya Abou Dargham,
Wang Yun,
Shi XueYin
Publication year - 2014
Publication title -
cns neuroscience and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 69
eISSN - 1755-5949
pISSN - 1755-5930
DOI - 10.1111/cns.12294
Subject(s) - excitatory postsynaptic potential , hippocampal formation , long term potentiation , inhibitory postsynaptic potential , propofol , neuroscience , neurotransmission , postsynaptic current , chemistry , morris water navigation task , postsynaptic potential , glutamate receptor , anesthesia , pharmacology , medicine , psychology , receptor
Summary Background Propofol is a short‐acting, intravenous general anesthetic that is widely used in clinical practice for short procedures; however, it causes depressed cognitive function for several hours thereafter. (R)‐alpha‐methylhistamine ( RAMH ), a selective histamine H3 receptor agonist, can enhance memory retention and attenuates memory impairment in rats. In this study, we investigated whether RAMH could rescue propofol‐induced memory deficits and the underlying mechanisms partaking in this process. Methods In the modified Morris water maze (MWM) test, rats were randomized into the following groups: control, propofol (25 mg/kg, i.p., 30 min before training), RAMH (10 mg/kg, i.p., 60 min before training), and propofol plus RAMH. All randomized rats were subjected to 2 days of training, and a probe test was conducted on day 3. Field excitatory postsynaptic potentials were recorded from CA1 neurons in rat hippocampal slices, and long‐term potentiation (LTP) was induced by either theta‐burst stimulation (TBS) or high‐frequency tetanic stimulation (HFS). Spontaneous and miniature inhibitory ( sIPSC s, mIPSC s) or excitatory ( sEPSC s, mEPSC s) postsynaptic currents were recorded from CA1 pyramidal neurons by whole‐cell patch clamp. Results In the MWM task, propofol injection significantly impaired spatial memory retention. Pretreatment with RAMH reversed propofol‐induced memory retention. In hippocampal CA1 slices, propofol perfusion markedly inhibited TBS‐ but not HFS‐induced LTP. Co‐perfusion of RAMH reversed the inhibitory effect of propofol on TBS‐induced LTP reduction. Furthermore, in hippocampal CA1 pyramidal neurons, RAMH significantly suppressed the frequency but not the amplitude of sIPSC s and mIPSC s and had little effects on both the frequency and amplitude of sEPSC s and mEPSC s. Conclusions Our results suggest that RAMH , by inhibiting presynaptic GABA ergic neurotransmission, suppresses inhibitory neurotransmission in hippocampal CA 1 pyramidal neurons, which in turn reverses inhibition of CA 1 LTP and the spatial memory deficits induced by propofol in rats.