Memory Impairment and Reduced Exploratory Behavior in Mice after Administration of Systemic Morphine

Kitanaka, Junichi; Kitanaka, Nobue; Hall, F. Scott; Fujii, Mei; Goto, Akiko; Kanda, Yusuke; Koizumi, Akira; Kuroiwa, Hirotoshi; Mibayashi, Satoko; Muranishi, Yumi; Otaki, Soichiro; Sumikawa, Minako; Tanaka, Keita; Nishiyama, Nobuyoshi; Uhl, George R.; Takemura, Masashi

doi:10.4137/jen.s25057

Cited by 37 publications

(27 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In the marble burying test, contrary to anxiolytic (Archer et al, ), antidepressant (Nicolas et al, ) and antipsychotic drugs (Bruins Slot et al, ), MXE increased burying behaviour at low and intermediate doses, with the maximal effect observed at 0.5 mg·kg −1 , while not inducing significant effects at higher doses. The effect of MXE we observed in this test is the opposite of that reported after acute exposure to nicotine (Anderson and Brunzell, ), morphine (Umathe et al, ; Kitanaka et al, ) and cannabinoids (Casarotto et al, ; Deiana et al, ) in mice. Quite unexpectedly, it is also dissimilar from that of NMDA receptor antagonists, which typically reduce marble‐burying behaviour (Egashira et al, ; Iijima et al, ).…”

Section: Discussioncontrasting

confidence: 81%

Methoxetamine affects brain processing involved in emotional response in rats

Zanda

Fadda

Antinori

et al. 2017

British J Pharmacology

View full text Add to dashboard Cite

BACKGROUND AND PURPOSEMethoxetamine (MXE) is a novel psychoactive substance that is emerging on the Internet and induces dissociative effects and acute toxicity. Its pharmacological effects have not yet been adequately investigated. EXPERIMENTAL APPROACHWe examined a range of behavioural effects induced by acute administration of MXE (0.5-5 mg·kg À1 ; i.p.) in rats and whether it causes rapid neuroadaptive molecular changes. KEY RESULTS MXE (0.5-5 mg·kgÀ1 ) affected motor activity in a dose-and time-dependent manner, inducing hypermotility and hypomotility at low and high doses respectively. At low and intermediate doses (0.5 and 1 mg·kg À1 ), MXE induced anxious and/or obsessive-compulsive traits (marble burying test), did not significantly increase sociability (social interaction test) or induce spatial anxiety (elevated plus maze test). At a high dose (5 mg·kg À1 ), MXE induced transient analgesia (tail-flick and hot-plate test), decreased social interaction time (social interaction test) and reduced immobility time while increasing swimming activity (forced swim test), suggesting an antidepressant effect. Acute MXE administration did not affect self-grooming behaviour at any dose tested. Immunohistochemical analysis showed that behaviourally active doses of MXE (1 and 5 mg·kg À1 ) increased phosphorylation of ribosomal protein S6 in the medial prefrontal cortex and hippocampus. CONCLUSIONS AND IMPLICATIONSMXE differentially affected motor activity, behaviour and emotional states in rats, depending on the dose tested. As reported for ketamine, phosphorylation of the ribosomal protein S6 was increased in MXE-treated animals, thus providing a 'molecular snapshot' of rapid neuroadaptive molecular changes induced by behaviourally active doses of MXE. Abbreviations

show abstract

Section: Discussioncontrasting

confidence: 81%

Methoxetamine affects brain processing involved in emotional response in rats

Zanda

Fadda

Antinori

et al. 2017

British J Pharmacology

View full text Add to dashboard Cite

show abstract

“…Spatial working memory was assessed by recording spontaneous alternation behavior during an 8 min session in a Y maze [ 22 ]. The sequence of arm entries and total number of entries were recorded.…”

Section: Methodsmentioning

confidence: 99%

Deposition of BACE-1 Protein in the Brains of APP/PS1 Double Transgenic Mice

Luo

Huang

et al. 2016

BioMed Research International

View full text Add to dashboard Cite

The main causes of Alzheimer's disease remain elusive. Previous data have implicated the BACE-1 protein as a central player in the pathogenesis of Alzheimer's disease. However, many inhibitors of BACE-1 have failed during preclinical and clinical trials for AD treatment. Therefore, uncovering the exact role of BACE-1 in AD may have significant impact on the future development of therapeutic agents. Three- and six-month-old female APP/PS1 double transgenic mice were used to study abnormal accumulation of BACE-1 protein in brains of mice here. Immunofluorescence, immunohistochemistry, and western blot were performed to measure the distributing pattern and expression level of BACE-1. We found obvious BACE-1 protein accumulation in 3-month-old APP/PS1 mice, which had increased by the time of 6 months. Coimmunostaining results showed BACE-1 surrounded amyloid plaques in brain sections. The abnormal protein expression might not be attributable to the upregulation of BACE-1 protein, as no significant difference of protein expression was observed between wild-type and APP/PS1 mice. With antibodies against BACE-1 and CD31, we found a high immunoreactive density of BACE-1 protein on the outer layer of brain blood vessels. The aberrant distribution of BACE-1 in APP/PS1 mice suggests BACE-1 may be involved in the microvascular abnormality of AD.

show abstract

“…This disparity in locomotor behavior may be due to differences in the size of the testing apparatus. Alternatively, there is some evidence that higher number of arm entries is associated with poor performance in the y-maze (Kitanaka et al, 2015; Ghafouri et al, 2016). This suggests that the increase in arm entries exhibited by the Control/GNX group may be related to their working memory impairments, but this needs to be confirmed experimentally.…”

Section: Discussionmentioning

confidence: 99%

Viral-mediated Zif268 expression in the prefrontal cortex protects against gonadectomy-induced working memory, long-term memory, and social interaction deficits in male rats

et al. 2017

View full text Add to dashboard Cite

In humans, some males experience reductions in testosterone levels, as a natural consequence of aging or in the clinical condition termed hypogonadism, which are associated with impaired cognitive performance and mood disorder(s). Some of these behavioral deficits can be reversed by testosterone treatment. Our previous work in rats reported that sex differences in the expression of the transcription factor Zif268, a downstream target of testosterone, within the medial prefrontal cortex (mPFC) mediates sex differences in social interaction. In the present study, we aimed to examine the effects of gonadectomy (GNX) in male rats on mPFC Zif268 expression, mood and cognitive behaviors. We also examined whether reinstitution of Zif268 in GNX rats will correct some of the behavioral deficits observed following GNX. Our results show that GNX induced a downregulation of Zif268 protein in the mPFC, which was concomitant with impaired memory in the y-maze and spontaneous object recognition test, reduced social interaction time, and depression-like behaviors in the forced swim test. Reinstitution of mPFC Zif268, using a novel adeno-associated-viral (AAV) construct, abrogated GNX-induced working memory and long-term memory impairments, and reductions in social interaction time, but not GNX-induced depression-like behaviors. These findings suggest that mPFC Zif268 exerts beneficial effects on memory and social interaction, and could be a potential target for novel treatments for behavioral impairments observed in hypogonadal and aged men with declining levels of gonadal hormones.

show abstract

Memory Impairment and Reduced Exploratory Behavior in Mice after Administration of Systemic Morphine

Cited by 37 publications

References 44 publications

Methoxetamine affects brain processing involved in emotional response in rats

Methoxetamine affects brain processing involved in emotional response in rats

Deposition of BACE-1 Protein in the Brains of APP/PS1 Double Transgenic Mice

Viral-mediated Zif268 expression in the prefrontal cortex protects against gonadectomy-induced working memory, long-term memory, and social interaction deficits in male rats

Contact Info

Product

Resources

About