Enriched Environment Ameliorates Cognitive Deficits and Locomotor Sensitization in Morphine-Withdrawn Rats Receiving Methadone Maintenance Treatment

2020 ◽  
Vol 79 (6) ◽  
pp. 437-444 ◽  
Author(s):  
Parastoo Akbari ◽  
Mahmoud Najafi ◽  
Ali-Mohammad Rezaei ◽  
Hossein Miladi-Gorji
Keyword(s):  
Object Recognition ◽  
Learning And Memory ◽  
Spatial Learning ◽  
Methadone Maintenance Treatment ◽  
Water Maze ◽  
Maintenance Treatment ◽  
Methadone Maintenance ◽  
Memory Deficits ◽  
Spatial Learning And Memory ◽  
Locomotor Sensitization

<b><i>Objective:</i></b> This study was designed to examine whether enriched environments (EE) would attenuate object recognition and spatial learning and memory deficits and locomotor sensitization induced by methadone maintenance treatment (MMT) in morphine-withdrawn rats. <b><i>Methods:</i></b> Male Wistar rats (170 ± 10 g) were injected with bi-daily doses (10 mg/kg, 12-h intervals) of morphine for 14 days. Rats receiving MMT were reared in the standard environment (SE) or EE during 30 days of morphine withdrawal. Then, the rats were tested for object recognition (the object recognition memory test, ORMT) and spatial learning and memory (the water maze) and then challenged with morphine (1 mg/kg, i.p.) and evaluated for locomotor activity (open-field box). <b><i>Results:</i></b> The results revealed that the dependent/saline/EE (D/Sal/EE) and D/methadone/EE (D/Meth/EE) rats exhibited significant preference for the new object (<i>p</i> = 0.006 and <i>p</i> = 0.049), spent more time in the target zone (<i>p</i> = 0.045 and <i>p</i> = 0.005) on the water maze, and displayed a lower level of distance traveled (<i>p</i> = 0.002 and <i>p</i> = 0.0001) compared to their control groups reared in SE. <b><i>Conclusions:</i></b> We conclude that exposure to EE could ameliorate the object recognition and spatial memory deficits and also decrease locomotor sensitivity in morphine-withdrawn rats receiving MMT. Thus, EE may be beneficial in the treatment of addiction during MMT.

scholarly journals Trigeminal Neuralgia Induced by Cobra Venom Leads to Cognitive Deficits Associated with Downregulation of CREB/BDNF Pathway

2017 ◽  
Vol 2 (20;2) ◽  
pp. 53-67
Author(s):  
Jianxiong An
Keyword(s):  
Cognitive Impairment ◽  
Trigeminal Neuralgia ◽  
Learning And Memory ◽  
Spatial Learning ◽  
Cognitive Deficits ◽  
Water Maze ◽  
Memory Deficits ◽  
Cobra Venom ◽  
Spatial Learning And Memory ◽  
Bdnf Pathway

Background: Chronic pain often results in cognitive impairment. Our previous study showed that trigeminal neuralgia induced by cobra venom leads to spatial learning and memory deficits, although the underlying mechanism remains unclear. However, recent evidence indicates that the c-AMP-responsive element binding protein (CREB)/brain derived neurotrophic factor (BDNF) pathway plays a critical role in various etiologies of cognitive deficits. Objectives: Our aim was to explore the CREB/BDNF pathway to determine the molecular mechanisms involved in the pathogenesis of cognitive impairment caused by cobra venominduced trigeminal neuralgia. Study Design: A randomized, controlled animal study. Setting: Department of Anesthesiology, Beijing Friendship Hospital, Capital Medical University. Methods: Fifty male Sprague–Dawley rats were randomly divided into 3 groups: cobra venom group, sham group, and control group. Cobra venom or saline was injected into the sheath of the infraorbital nerve (ION), respectively. Video recordings and mechanical thresholds were used to analyze changes in behavioral activity 3 days before surgery and 4, 7, 14, 21, 28, and 56 days after surgery. Morris water maze tests were conducted at 4- and 8-week time points after surgery to evaluate spatial learning and memory. We also investigated expression changes of phosphorylated CREB (p-CREB) and BDNF in the hippocampus and prefrontal cortex (PFC) using western blotting and immunohistochemistry. Results: Cobra venom-treated rats exhibited significant changes in face grooming, as well as exploratory and resting behaviors, compared with the control group and sham group (both P < 0.001). Rats in the cobra venom group exhibited slightly impaired acquisition (P < 0.05) without memory deficits (P > 0.05) in the first water maze protocol. In the second water maze test, rats in the cobra venom group exhibited spatial learning and memory deficits, with fewer platform site crossings during the probe trial (P < 0.05). Moreover, results showed decreased p-CREB and BDNF expressions in the hippocampus and PFC in the cobra venom group, with significant differences at 9 weeks post-surgery (P < 0.05). Limitations: No signaling inhibitor or genetic manipulation was administered to further confirm upstream factors of the CREB/BDNF pathway in cognitive deficits caused by chronic trigeminal neuralgia. Conclusions: The findings suggest that cognitive impairment caused by cobra venom-induced trigeminal neuralgia is associated with downregulation of the CREB/BDNF pathway in the hippocampus and PFC. Key words: Cognitive impairment, the CREB/BDNF pathway, cobra venom, trigeminal neuralgia, hippocampus, prefrontal cortex, free behavior, Morris water maze

A cAMP analog attenuates beta-amyloid (1–42)-induced mitochondrial dysfunction and spatial learning and memory deficits

2018 ◽  
Vol 140 ◽  
pp. 34-42 ◽  
Author(s):  
Mehdi Aghsami ◽  
Mohammad Sharifzadeh ◽  
Mohammad Reza Sepand ◽  
Meysam Yazdankhah ◽  
Seyed Afshin Seyednejad ◽  
...  
Keyword(s):  
Mitochondrial Dysfunction ◽  
Learning And Memory ◽  
Spatial Learning ◽  
Beta Amyloid ◽  
Memory Deficits ◽  
Spatial Learning And Memory ◽  
Camp Analog ◽  
Learning And Memory Deficits

scholarly journals Selective memory and behavioral alterations after ambient ultrafine particulate matter exposure in aged 3xTgAD Alzheimer’s disease mice

2019 ◽  
Vol 16 (1) ◽  
Author(s):  
Katrina Jew ◽  
Denise Herr ◽  
Candace Wong ◽  
Andrea Kennell ◽  
Keith Morris-Schaffer ◽  
...  
Keyword(s):  
Locomotor Activity ◽  
Learning And Memory ◽  
Spatial Learning ◽  
Short Term Memory ◽  
Memory Deficits ◽  
Olfactory Discrimination ◽  
Spatial Learning And Memory ◽  
Short Term ◽  
Term Memory ◽  
Appetitive Motivation

Abstract Background A growing body of epidemiological literature indicates that particulate matter (PM) air pollution exposure is associated with elevated Alzheimer’s disease (AD) risk and may exacerbate AD-related cognitive decline. Of concern is exposure to the ultrafine PM (UFP) fraction (≤100 nm), which deposits efficiently throughout the respiratory tract, has higher rates of translocation to secondary organs, like brain, and may induce inflammatory changes. We, therefore, hypothesize that exposure to UFPs will exacerbate cognitive deficits in a mouse model of AD. The present study assessed alterations in learning and memory behaviors in aged (12.5 months) male 3xTgAD and non-transgenic mice following a 2-week exposure (4-h/day, 4 days/week) to concentrated ambient UFPs using the Harvard ultrafine concentrated ambient particle system (HUCAPS) or filtered air. Beginning one month following exposure, locomotor activity, spatial learning and memory, short-term recognition memory, appetitive motivation, and olfactory discrimination were assessed. Results No effects on locomotor activity were found following HUCAPS exposure (number concentration, 1 × 104–4.7 × 105 particles/cm3; mass concentration, 29–132 μg/m3). HUCAPS-exposed mice, independent of AD background, showed a significantly decreased spatial learning, mediated through reference memory deficits, as well as short-term memory deficits in novel object recognition testing. AD mice displayed diminished spatial working memory, potentially a result of olfactory deficits, and short-term memory. AD background modulated HUCAPS-induced changes on appetitive motivation and olfactory discrimination, specifically enhancing olfactory discrimination in NTg mice. Modeling variation in appetitive motivation as a covariate in spatial learning and memory, however, did not support the conclusion that differences in motivation significantly underlie changes in spatial learning and memory. Conclusions A short-term inhalation exposure of aged mice to ambient UFPs at human-relevant concentrations resulted in protracted (testing spanning 1–6.5 months post-exposure) adverse effects on multiple memory domains (reference and short-term memory) independent of AD background. Impairments in learning and memory were present when accounting for potential covariates like motivational changes and locomotor activity. These results highlight the need for further research into the potential mechanisms underlying the cognitive effects of UFP exposure in adulthood.

The effect of early experience on water maze spatial learning and memory in rats

1990 ◽  
Vol 23 (5) ◽  
pp. 427-439 ◽  
Author(s):  
Richard C. Tees ◽  
Kristin Buhrmann ◽  
Jordan Hanley
Keyword(s):  
Learning And Memory ◽  
Spatial Learning ◽  
Water Maze ◽  
Early Experience ◽  
Spatial Learning And Memory
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