Effects of endurance, resistance, and concurrent exercise on learning and memory after morphine withdrawal in rats
Introduction
Morphine addiction is a serious health problem throughout the world [3]. Although clearly effective, morphine is useful only for the treatment of chronic pain because of the rapid development of tolerance, dependence, and addiction that occurs through neuronal and synaptic alterations in the brain, especially within the hippocampus [11]. Although morphine is widely used, information regarding the associated mental health deficits is limited [15], [49].
Learning and memory are complex brain functions that are dependent upon specific central nervous system structures. In particular, the hippocampus and amygdala are critical for learning- and memory-related data processing and information storage [26]. Memory is categorized as long-term or short-term, based on the duration of memory storage. Short-term memory occurs over several minutes or less, during which information remains accessible before being either dismissed or transferred to long-term memory. Long-term memory is the brain's system for storing, managing, and retrieving information over periods ranging from several days to many years (i.e., lifetime memory) [30], [39]. In recent years, the effects of morphine on learning and memory have attracted significant attention. Morphine exerts serious effects on brain regions involved in cognitive functions such as learning and memory [27]. Several studies have indicated that μ-opioid receptors in the hippocampus play a vital role in learning and memory [7], [19]. Morphine preferentially binds to μ-opioid receptors, which are highly expressed in hippocampal cells [21]. According to several studies, chronic morphine administration can damage neurons by increasing oxidative stress [14], [50] and reduce long-term potentiation in the hippocampus through synaptic modification [5], [25]. Other studies show that disorders associated with morphine usage affect the performance of adult rats on different learning and memory tasks through unknown mechanisms [42], [44].
Importantly, mental health [36] and memory acquisition [47] are affected by exercise. In contrast to morphine, exercise has been shown to exert positive effects on learning and [2]. Furthermore, previous studies have shown distinct impacts of different kinds of physical activity on memory and neuronal compatibility in different brain areas [22]. For example, Afzalpour et al. showed that different types of exercise exert discrete effects on the expression of brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor, inflammatory proteins, and reactive oxygen species in the rat brain [1]. Therefore, the aim of the present study is to determine which type of exercise (endurance, strength, or concurrent (combined resistance and strength)) elicits the greatest effects on learning and memory impairments induced by morphine exposure in Wistar rats. To date, no study of this type has been conducted.
Section snippets
Animals
Forty male Wistar rats (150–180 g), aged six weeks, were housed at five animals per cage under a 12-hour light/dark cycle at stable room temperature (22 ± 1 °C) with 55 ± 3% relative humidity. Animals were given free access to standard mouse chow and tap water. The treatment protocols were set up in accordance with National Institutes of Health Guide for the Care and Use of Laboratory Animals as well as approved by the Institutional Animal Care and Use Committee at Hamadan University of Medical
Morris water maze
The acquisition data obtained during four days of training in the MWM are illustrated in Fig. 2. There was an insignificant interaction between exercise, morphine and days (F3, 34 = 1.4, P = 0.1) in the mean escape latency. As well as, there was insignificant interaction between exercise and days (F3, 42 = 0.6, P = 0.3) in the mean escape latency, but there was a significant interaction between exercise and morphine (F1, 46 = 12.1, P = 0.001). The mean escape latency showed a marked decrease over the four
Discussion
This study revealed a spatial learning deficit during the acquisition phase in sedentary morphine-dependent rats, as indicated by an increase in the mean escape latency in the MWM. Exercise, regardless of type, blocks this morphine-induced deficit, restoring spatial learning performance to levels equivalent to those of healthy, non-addicted rats. The spatial learning deficit during the retention phase was similar to that observed during the acquisition phase. The percentage of time spent in the
Conclusions
Based on the results of this study, we conclude that different forms of exercise exert similar effects on spatial learning and memory but differentially affect aversive learning and memory. This work suggests that varied types of exercise have diverse impacts on different learning and memory capabilities. Furthermore, morphine dependence-related cognitive impairments were reduced or blocked by exercise. Thus, different exercise regimens, especially combined training, may represent useful
Conflict of interest
There is no conflict of interest.
Acknowledgment
The authors would like to express their gratitude to the staff of the Neurophysiology Research Center for helping us to carry out this project. This research was supported by a grant (Grant Number: 9406173163) of the Hamadan University of Medical Sciences, Hamadan, Iran.
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