Effect of Nucleus Basalis Magnocellularis Lesions on Memory and Hippocampal Brain-Derived Neurotrophic Factor, IL-1β, Glucose, and Corticosterone Levels in Adult Rats

   Background: The nucleus basalis magnocellularis (NBM) sends projections to the hippocampus that are implicated in learning and memory formation. Despite ample evidence proposing that cognitive function impairment related to neurodegeneration, it may result from alteration of biochemical substances. We aimed to investigate the effects of NBM lesions on the hippocampal interleukin-1beta (IL-1β), brain-derived neurotrophic factor (BDNF), and corticosterone levels, as inflammation markers, and hallmarks of neurodegeneration, stress, and metabolic status. Methods: Thirty-six male Wistar rats were randomly put in control, sham, and NBM-lesioned groups. After inducing the lesion using an intra-NBM injection of 10 μg ibotenic acid (5 μg/μL, each side) in rats, memory was estimated using the passive avoidance test. Moreover, serum and hippocampal IL-1β levels, as well as the hippocampal corticosterone, BDNF, and glucose levels were measured after 42 days. Results: Findings indicated a significant impairment of retention at different intervals in the NBM-lesioned group. BDNF decreased whereas corticosterone, glucose, and IL-1β levels increased in the hippocampus. Also, the levels of serum IL-1β, hippocampal BDNF, corticosterone, and glucose had significant correlations with hippocampal IL-1β levels. Conclusion: The synchronous alterations of some hippocampal factors, including BDNF, corticosterone, IL-1β, and glucose, caused by NBM lesion suggest that their interaction might play a significant role in neurodegeneration and relevant learning and memory impairments

The Protective Effects of Crocin on Input-Output Functions and Long-term Potentiation of Hippocampal CA1 Area in Rats Exposed to Chronic Social Isolated Stress

Introduction: The lack of social communication is associated with the primary risk of proper brain functions. It is reported that crocin helps relieve this problem. The present study examined the protective effect of two doses of crocin on Long-term potentiation (LTP) of hippocampal cornu ammonis 1 (CA1) area as a cellular mechanism in rats exposed to chronic social isolated stress. Methods: Rats were assigned to the control, sham, isolation stress, and two stress groups (receiving 30 and 60 mg/kg crocin). Chronic isolation stress (CIS) was induced 6 h/d, and crocin was administrated for 21 days. The field excitatory postsynaptic potential (fEPSP) slope and amplitude were measured by input/output functions and LTP induction in the CA1 area of the hippocampus. Also, the corticosterone and glucose levels were assayed in the hippocampus and frontal cortex. Results: The slope and amplitude of fEPSP severity were impaired in both input/output and LTP responses in the CIS group. Crocin at a dose of 30 and particularly 60 mg/kg improved input/output and LTP responses in the CIS group. Also, the corticosterone levels significantly increased in the frontal cortex and especially the hippocampus. In contrast, only a high dose of crocin decreased hippocampal corticosterone levels in the CIS condition. Finally, the glucose levels did not change in the hippocampus and frontal cortex in all experimental groups.  Conclusion: The chronic isolation stress impaired neural excitability and Long-term plasticity in the CA1 area due to elevated corticosterone in the hippocampus and probably the frontal cortex. The low and high doses of crocin improved excitability and Long-term plasticity in the chronic isolation stress group by only decreasing corticosterone levels in the hippocampus, but not the frontal cortex

The role of GABAB receptors in morphine self-administration

Background: There is only little information about the effects of GABA receptors agonist and antagonist on morphine self-administration. Present study was designed to assess role of GABAB receptors in the regulation of morphine-reinforced self-administration. Methods: This study was performed in four groups of rats: (1) Saline group, which received saline in the self-administration session. (2) Morphine group, which received morphine in saline solution in the self-administration session. (3) Baclofen + Morphine group, which received both baclofen 20 min before self- administration test and morphine in the self-administration session. (4) Phaclofen + Morphine group, which received both phaclofen 20 min before self- administration test and morphine in the self-administration session. The number of lever pressing and self-infusion were recorded. Results: Morphine significantly increased the number of active lever pressing dose dependently in self-administration session in comparative with saline group. Administration of baclofen, 20 min before morphine self-administration produced significant decrease in the initiation of morphine self-administration during all session. Conversely, pre-treatment of phaclofen increased the number of active lever pressing and self-infusion in this test. Conclusion: Our results indicated a short-term treatment by baclofen, reduced morphine-maintenance response in a dose-dependent manner, suggesting that GABAB receptor agonists could be useful for reversing the neuroadaptations related to opiates

Blockade of Glutamate Receptors within the Prelimbic Cortex Attenuate Concentration of Excitatory Amino Acids in the Morphine Self-administration in Rats

Background: The attitude of research on addiction has been done on the key role of glutamate. As a regard, the prelimbic cortex (PrL) has an important role in addiction, learning, and memory. We tried to investigate the level of glutamate and aspartate concentration after glutamate receptors blockade in this region in the morphine-addicted rats. Materials and Methods: In this study, we examined the effects of local infusion of the N-methyl-D-aspartate receptor and α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor antagonists, 2-amino-5-phosphonovaleric acid (AP5), and 6-cyano-7-nitroquinoxaline-2, 3-dione (CNQX), into the PrL cortex on the level of excitatory amino acids (EAAs) and glycine. After 11 days of self-administration, the prelimbic area of the brain was taken out, and the EAAs and glycine concentration was measured by high-performance liquid chromatography. Results: Morphine resulted in the significant increase in the EAAs concentration within this area (P ≤ 0.001). Microinjection of AP5 into this region before using of morphine significantly decreased the morphine-induced glutamate and aspartate concentration (P ≤ 0.001). CNQX had the same effect and significantly reduced the EAAs concentration compared to the morphine group (P ≤ 0.001). In addition, microinjection of AP5 and CNQX simultaneously increased glycine concentration (P ≤ 0.001). Conclusions: These results show that morphine stimulates the EAAs release in the prelimbic area. It seems that microinjection of AP5 or CNQX in this region is effective in reducing morphine-induced EAA. It is suggested that EAA transmission in the PrL cortex may be a possible target for treatment of morphine addiction

EFFECT OF EXERCISE ON LEARNING, MEMORY AND LEVELS OF EPINEPHRINE IN RATS' HIPPOCAMPUS

The aim of the present study was to investigate effect of exercise on learning and memory, long-term potentiation and levels of epinephrine in the rat hippocampus. Treadmill trained (one hour at 17 m·min-1 for 10 days) and corresponding control rats went through spatial learning process on a Morris water maze for 8 days. The time to reach the platform (latency), the length of swim path, and the swim speed were used for the evaluation of spatial learning. Our results showed that physical activity produced a significant enhancement in spatial learning, with a decreased path length (p<0.05) and latency (p<0.05) to the platform in Morris water maze, without affecting the swim speed. Furthermore, the levels of the epinephrine were significantly increased (p<0.05) in hippocampus of the exercised rats. In conclusion our findings suggest that the enhanced learning by exercise may be mediated through the activation of adrenoceptors in the hippocampus and epinephrine may play an important role in potentiation of learnin

Chronic treatment with carvacrol improves passive avoidance memory in a rat model of Parkinson's disease

ABSTRACT The present study investigated the effects of carvacrol on motor and memory deficits as well as hyperalgesia in the 6-OHDA-lesioned rat model of Parkinson's disease. The animals were subjected to unilateral microinjection of 6-OHDA into the medial forebrain bundle and treated with carvacrol (25, 50 and 100 mg/kg, ip) for six weeks after surgery. The 6-OHDA-lesioned rats showed contralateral rotations towards the lesion side, which was accompanied by learning and memory deficits in a passive avoidance test and a decrease in tail withdrawal latency in a tail flick test at the end of week 6. The results also showed that treatment with carvacrol at a dose of 25 mg/kg ameliorated memory deficits, with no effect on rotations and hyperalgesia in lesioned rats. In conclusion, carvacrol improves memory impairments in rats with Parkinson's disease; therefore, it may serve as an adjunct therapy for the alleviation of memory deficits in Parkinson's disease patients

Electrical stimulation of prelymbic with different currents intensities on morphine induced spatial memory deficit in rats

Background: The medial prefrontal cortex (mPFC) is a part of brain reward system involved in cognitive functions such as learning and memory. Previous studies showed that electrical stimulation of prelymbic produced different effects on morphine-induced condition place preference. In this study, we investigated the electrical stimulation with different current intensities on spatial memory in rats. Materials and Methods: In this study, male Wister rats weighing approximately 200–300 g were used. The effect of prelymbic electrical stimulation with 25 and 150 μA currents intensities in healthy and addicted rats on spatial memory was studied. Spatial memory was investigated using the Morris water maze test in addicted rats after 9 days of electrical stimulation. Results: Our findings have shown that morphine reduces the memory and learning, whereas the present results indicated that electrical stimulation of prelymbic area with current intensity of the 25 μA shortened the time and distance to reach to platform that indicated improvement in spatial memory on addicted rats. Whereas the electrical stimulation of prelymbic area with the current intensity of 150 μA has special weakening effects on spatial memory and prolongs the time and distance to reach the platform. Conclusions: The electrical stimulations of prelymbic with 25 μA current intensity improved the spatial memory in addicted rats while with 150 μA current intensity weakened spatial memory in rats. It is possible that increase in the release of some neurotransmitters reverses the effect of morphine on spatial memory

Effect of Aerobic Exercise on Morphine Self-administration and Pain Modulation in Rats

Background: Exercise reverses retention deficit induced by morphine. The present study investigated the effect of aerobic exercise on tolerance to morphine usage and pain modulation. Materials and Methods: Male Wistar rats were divided into four groups as follows: (1) saline group (S), (2) morphine group (M), (3) saline + exercise (S + E), and (4) morphine + exercise group (M + E). The rats were initially trained to receive small pellets of food by pressing an active lever in the self-administration apparatus. The tail-flick and hot-plate tests were used for pain assessment. To perform the experiment, the jugular vein was exposed and cannulated. After recovery, the animals were placed in the self-administration apparatus and allowed to self-administer morphine in 2 h sessions over 11 consecutive days. Results: The morphine group was found to record a higher number of active lever pressings than did the saline one while this parameter decreased in the morphine + exercise group compared with the morphine one. Moreover, the morphine + exercise exhibited lowered pain sensitivity as evidenced to have reduced morphine use in the hot plate test. Conclusion: The exercise might be suggested to reduce using of morphine and modulate pain probably through the release of endogenous opioid

The effect of treadmill running on passive avoidance learning in animal model of Alzheimer disease

Background : Alzheimer′s disease was known as a progressive neurodegenerative disorder in the elderly and is characterized by dementia and severe neuronal loss in the some regions of brain such as nucleus basalis magnocellularis. It plays an important role in the brain functions such as learning and memory. Loss of cholinergic neurons of nucleus basalis magnocellularis by ibotenic acid can commonly be regarded as a suitable model of Alzheimer′s disease. Previous studies reported that exercise training may slow down the onset and progression of memory deficit in neurodegenerative disorders. This research investigates the effects of treadmill running on acquisition and retention time of passive avoidance deficits induced by ibotenic acid nucleus basalis magnocellularis lesion. Methods : Male Wistar rats were randomly selected and divided into five groups as follows: Control, sham, Alzheimer, exercise before Alzheimer, and exercise groups. Treadmill running had a 21 day period and Alzheimer was induced by 5 μg/μl bilateral injection of ibotenic acid in nucleus basalis magnocellularis. Results : Our results showed that ibotenic acid lesions significantly impaired passive avoidance acquisition ( P < 0.01) and retention ( P < 0.001) performance, while treadmill running exercise significantly ( P < 0.001) improved passive avoidance learning in NBM-lesion rats. Conclusion : Treadmill running has a potential role in the prevention of learning and memory impairments in NBM-lesion rats