Reduced dorsal hippocampal glutamate release significantly correlates with the spatial memory deficits produced by benzodiazepines and ethanol

Shimizu, Keiko; Matsubara, Kazuo; Uezono, Takumi; Kimura, Kojiro; Shiono, Hiroshi

doi:10.1016/s0306-4522(97)00339-4

Cited by 85 publications

(45 citation statements)

References 33 publications

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“…Our finding of memory impairment in NPY-tg subjects is therefore in agreement with these in vitro data and may be attributable to an enhanced Y2-mediated inhibition of excitatory synaptic activity. Interestingly, both at the level of hippocampal neurotransmission and of integrated memory function, the effects of NPY are similar to those observed when hippocampal glutamate release is inhibited by benzodiazepines or ethanol (44).…”

Section: Discussionsupporting

confidence: 54%

Behavioral insensitivity to restraint stress, absent fear suppression of behavior and impaired spatial learning in transgenic rats with hippocampal neuropeptide Y overexpression

Thorsell

Michalkiewicz

Dumont

et al. 2000

Proc. Natl. Acad. Sci. U.S.A.

285

192

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Exogenous neuropeptide Y (NPY) reduces experimental anxiety in a wide range of animal models. The generation of an NPYtransgenic rat has provided a unique model to examine the role of endogenous NPY in control of stress and anxiety-related behaviors using paradigms previously used by pharmacological studies. Locomotor activity and baseline behavior on the elevated plus maze were normal in transgenic subjects. Two robust phenotypic traits were observed. (i) Transgenic subjects showed a markedly attenuated sensitivity to behavioral consequences of stress, in that they were insensitive to the normal anxiogenic-like effect of restraint stress on the elevated plus maze and displayed absent fear suppression of behavior in a punished drinking test. (ii) A selective impairment of spatial memory acquisition was found in the Morris water maze. Control experiments suggest these traits to be independent. These phenotypic traits were accompanied by an overexpression of prepro-NPY mRNA and NPY peptide and decreased NPY-Y1 binding within the hippocampus, a brain structure implicated both in memory processing and stress responses. Data obtained using this unique model support and extend a previously postulated anti-stress action of NPY and provide novel evidence for a role of NPY in learning and memory.anxiety ͉ amygdala N europeptide Y (NPY) (1) is highly expressed in the mammalian brain. Its pharmacological administration into the central nervous system reduces experimental anxiety in a wide range of animal models (2-5), but its involvement in memory function is less clear. NPY receptors cloned to date all belong to the superfamily of G protein-coupled receptors but differ in their ligand affinity profiles. The NPY-Y1 receptor (6-8) requires the intact NPY sequence for recognition and activation, and seems to be the subtype mediating anti-anxiety actions of NPY (3-5, 9, 10). The Y2 receptor subtype is also activated by C-terminal fragments of NPY, such as NPY 13-36 (11). The highest number of NPY-binding sites, predominantly of the Y2 subtype, is found within the hippocampus. Activation of Y2 receptors within this structure has been shown to suppress hippocampal glutamatergic transmission through presynaptic mechanisms (12, 13), but the behavioral consequences of Y2 signaling in this area are unclear.In agreement with anti-stress effects observed following central administration of NPY, a role for endogenous NPY in control of stress and anxiety-related behaviors is suggested by several findings. Acute physical restraint, which promotes experimental anxiety (14), suppresses NPY mRNA and peptide levels within the amygdala and cortex. In contrast, repeated exposure to the same stressor once daily for 10 days leads to a complete behavioral and endocrine habituation, accompanied by an up-regulation of amygdala NPY expression (15). We have therefore proposed that an up-regulation of NPY expression may contribute to the behavioral adaptation to stress. This extends a hypothesis that NPY may act to ''buffer'' behavioral effects of st...

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Section: Discussionsupporting

confidence: 54%

Behavioral insensitivity to restraint stress, absent fear suppression of behavior and impaired spatial learning in transgenic rats with hippocampal neuropeptide Y overexpression

Thorsell

Michalkiewicz

Dumont

et al. 2000

Proc. Natl. Acad. Sci. U.S.A.

285

192

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show abstract

“…In this animal model, we employed the Morris water maze test combined with the brain microdialysis technique to verify anterograde amnesia produced by alcohol combined with benzodiazepines. This combination of neurodepressive agents specifically reduces neural transmission of glutamate in the dorsal hippocampal sites, thus inhibiting spatial memory formation to induce anterograde amnesia [17]. These findings strongly support that claims of anterograde amnesia due to triazolam action by victims are not fabrications or false impressions, but are in fact verified behaviorally, pharmacologically, and neurologically.…”

Section: Discussionsupporting

confidence: 64%

“…We have previously reported that anterograde amnesia frequently occurs after taking benzodiazepines and ethanol in a rat model [17]. In that investigation, we studied in vivo hippocampal presynaptic glutamate transmission in conjunction with memory deficits induced by benzodiazepines and ethanol in rats as an animal model of amnesia, and found that significant decreases in hippocampal glutamate transmission closely correlated with the extent of impairment of spatial memory performance.…”

Section: Introductionmentioning

confidence: 93%

Triazolam Impairs Avoidance Reaction-A Scientific Proof Why the Victim does not Escape from Drug-Facilitated Sexual Assaults

Shimizu¹,

Ohmura²,

Okuda³

2016

J Foren Psy

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Following closely behind levels in Western countries, the number of drug-facilitated sexual assaults (DFSAs), involving the illicit use of medicine, has been recently increasing in Japan. Tirazolam is the most frequently used date-rape drug in DFSAs occurring in Japan. In this study, the effect of triazolam on behavior in response to fear and anxiety was evaluated using an elevated plus-maze test in mice. Triazolam-treated animals (0.01 mg/kg) showed no significant difference in total locomotor activity compared with vehicle-treated mice (controls). On the contrary, activity levels on the open arms of the apparatus (time spent, mean value of movement), where mice would normally feel anxiety or fear, were significantly increased in triazolam-treated mice compared with controls. However, total locomotor activities on the plus-maze were not different between two groups, indicating that sedation was not induced by tirazolam under these conditions. These results suggest that triazolam treatment led the mice to become insensitive to fear and anxiety; their defence reactions were impaired. We conclude that this finding provides scientific evidence in reply to defence arguments presented in court trials that there is little or no evidence of the victim attempting to escape from a sexual assault. Additionally, the finding is as true of other benzodiazepine receptor agonists as of triazolam.

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“…It is obvious from these findings that ethanol potentiates the triazolam-induced memory deficits on not only the acquisition process but also the retrieval process of memory. Shimizu et al (10) emphasized that the reduction of glutamate neuronal transmission in the dorsal hippocampus induced by triazolam is strongly correlated with the extent of spatial memory deficits. It was found that ethanol also reduced the release of glutamate in the hippocampus (10,12), although an increase in total error was not observed in our present study.…”

Section: Discussionmentioning

confidence: 99%

“…Shimizu et al (10) emphasized that the reduction of glutamate neuronal transmission in the dorsal hippocampus induced by triazolam is strongly correlated with the extent of spatial memory deficits. It was found that ethanol also reduced the release of glutamate in the hippocampus (10,12), although an increase in total error was not observed in our present study. It is generally recognized that glutamate is largely related with both acquisition and retrieval of memory.…”

Section: Discussionmentioning

confidence: 99%

Potentiation of Ethanol in Spatial Memory Deficits Induced by Some Benzodiazepines

et al. 2006

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Abstract. Triazolam caused no significant increase in the total error at 0.05 and 0.1 mg / kg. However, at 0.2 mg / kg, it caused a significant increase in total error. Almost the same findings were observed with brotizolam and rilmazafone. That is, at 0.2 and 0.5 mg / kg of brotizolam, 0.5 and 1.0 mg / kg of rilmazafone caused no significant increase in the total error. However, brotizolam at 1.0 mg / kg and rilmazafone at 2.0 mg / kg caused a significant increase in total error. Triazolam (0.05 mg / kg) and ethanol (1.0 g / kg) showed no significant effect on the numbers of errors when used alone separately, but the simultaneous use of triazolam and ethanol caused a significant increase in total error. Almost the same findings were observed with the coadministration of brotizolam (0.2 mg / kg) or rilmazafone (0.5 mg / kg) with ethanol. These results clearly indicate that all the short-acting benzodiazepines used in the study showed potentiation by ethanol in spatial memory deficits in mice.

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Reduced dorsal hippocampal glutamate release significantly correlates with the spatial memory deficits produced by benzodiazepines and ethanol

Cited by 85 publications

References 33 publications

Behavioral insensitivity to restraint stress, absent fear suppression of behavior and impaired spatial learning in transgenic rats with hippocampal neuropeptide Y overexpression

Behavioral insensitivity to restraint stress, absent fear suppression of behavior and impaired spatial learning in transgenic rats with hippocampal neuropeptide Y overexpression

Triazolam Impairs Avoidance Reaction-A Scientific Proof Why the Victim does not Escape from Drug-Facilitated Sexual Assaults

Potentiation of Ethanol in Spatial Memory Deficits Induced by Some Benzodiazepines

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