(R)‐alpha‐methylhistamine Suppresses Inhibitory Neurotransmission in Hippocampal CA1 Pyramidal Neurons Counteracting Propofol‐Induced Amnesia in Rats

Abstract

Our results suggest that RAMH, by inhibiting presynaptic GABAergic neurotransmission, suppresses inhibitory neurotransmission in hippocampal CA1 pyramidal neurons, which in turn reverses inhibition of CA1 LTP and the spatial memory deficits induced by propofol in rats.

Reduced Cyclic Adenosine Monophosphate Level in Hippocampal CA1 Participates in Propofol Induced Amnesia in Rats

“…In the present study, we obtained several sets of data about the role of the key molecular cAMP in the propofol induced LTP inhibition and memory impairment. First, consistent with the results that propofol inhibited cAMP dependent LTP in the hippocampal CA1 region (Nagashima et al, 2005 ; Li et al, 2014 ), propofol inhibited the FSK induced LTP in the hippocampal CA1 region. It further endorsed the assumption that propofol inhibited cAMP signaling induced CA1 LTP.…”

“…Long-term potentiation (LTP), which is the long-lasting increase in synaptic strength following trains of stimuli, has been proposed to be as a cellular mechanism of memory formation in the brain (Eichenbaum, 1996 ; Miller and Mayford, 1999 ). Previous researches from ourselves and others found that propofol could inhibit theta burst stimulation induced hippocampal CA1 LTP in both rats and mice (Nagashima et al, 2005 ; Takamatsu et al, 2005 ; Li et al, 2014 ), but had little effect on the CA1 LTP evoked by high frequency stimulations (Li et al, 2014 ). It has been proved that different protocols induced LTP have different underlying molecular mechanisms (Nguyen and Kandel, 1997 ; Staubli et al, 1999 ; Costa and Grybko, 2005 ; Li et al, 2014 ).…”

“…Previous researches from ourselves and others found that propofol could inhibit theta burst stimulation induced hippocampal CA1 LTP in both rats and mice (Nagashima et al, 2005 ; Takamatsu et al, 2005 ; Li et al, 2014 ), but had little effect on the CA1 LTP evoked by high frequency stimulations (Li et al, 2014 ). It has been proved that different protocols induced LTP have different underlying molecular mechanisms (Nguyen and Kandel, 1997 ; Staubli et al, 1999 ; Costa and Grybko, 2005 ; Li et al, 2014 ). For example, theta burst stimulation induced LTP in hippocampal CA1 region is reported cAMP signaling dependent and sensitive to be affected by GABA receptor activation (Nguyen and Kandel, 1997 ; Staubli et al, 1999 ; Costa and Grybko, 2005 ).…”

“…The detailed protocol for recording field excitatory post-synaptic potentials (fEPSPs) had been described previously (Li et al, 2014 ). The brain slices were perfused with normal oxygenated ACSF, which contained (in mM): 126 NaCl, 2.5 KCl, 1.0 NaH 2 PO 4 , 26 NaHCO 3 , 2.5 CaCl 2 , 1.3 MgCl 2 , and 10.0 glucose, with the pH adjusted to 7.4.…”

Activation of histamine H3 receptor decreased cytoplasmic Ca2+ imaging during electrical stimulation in the skeletal myotubes

“…H 3 receptor functional analysis, using an H 3 receptor agonist (R)-α-MeHA, revealed that in fully differentiated 7-day myotubes, H 3 receptor activation decreased Ca 2 þ imaging evoked by electrical stimulation. The lowest (R)-α-MeHA concentration used (1 nM) was below the agonist affinity for H 3 receptor (pK i ¼ 8.4) in the brain (Chen et al, 2003 andLi et al, 2014) and had no effect on the cytoplasmic Ca 2 þ imaging under electrical stimulation in our study. On the other hand, the highest (R)-α-MeHA concentration used (100 μM) was also less active, probably because of combinatorial effects, due to nonspecific activation of other receptors (H 1 receptor or H 2 receptor) on the cell membrane (Chen et al, 2015), which counteracted the response (Leurs et al, 1998), or probably as a self-protective mechanism.…”