lithium-chloride and Memory-Disorders

Aging is a phenomenon that all living organisms surely face. d-galactose (D-gal) has been used to develop an aging model of brain. Lithium (Li) has been proposed to have neuroprotective properties in relation to several neurological disorders. The goal of the current studyis to evaluate the effect of Lithium Chloride (LiCl) on D-gal induced neurological disorders and oxidative stress.. Rats were treated with D-gal at a dose of 300 mg/ml/kg and various doses of LiCl (20, 40 and 80 mg/ml/kg) for 14 days. After that behavioral analysis (Elevated plus maze (EPM); Light dark box test (LDT); Morris water maze (MWM); Forced swim test (FST)) were performed. Animals were decapitated after behavioral tests and brain samples were collected for biochemical (malondialdehyde (MDA); superoxide dismutase (SOD); catalase (CAT); glutathione peroxidase (GPx); acetylcholiesterase (AChE)) and neurochemical analysis (5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA)).. The results showed that administration of LiCl at all doses ameliorates D-gal induced, decreased time spent in the open arm and light box in EPM and LDT respectively, increased immobility in FST, increased latency escape in MWM, increased MDA levels, decreased antioxidant enzyme, increased AChE activity and decreased 5-HT metabolism.. In conclusion, the present study indicated that D-gal induced anxiety/depression like symptoms and memory impairment were ameliorated by LiCl (at all doses) possibly via its antioxidant effects and normalizing 5-HT function.

Topics: Aging; Animals; Antioxidants; Behavior, Animal; Brain; Galactose; Lithium Chloride; Male; Maze Learning; Memory Disorders; Neuroprotective Agents; Oxidative Stress; Rats; Rats, Sprague-Dawley; Serotonin

Advancements in fetal intervention procedures have led to increases in the number of pregnant women undergoing general anesthesia during the second trimester-a period characterized by extensive proliferation of fetal neural stem cells (NSCs). However, few studies have investigated the effects of mid-gestational sevoflurane exposure on fetal NSC proliferation or postnatal learning and memory function. In the present study, pregnant rats were randomly assigned to a control group (C group), a low sevoflurane concentration group (2%; L group), a high sevoflurane concentration group (3.5%; H group), a high sevoflurane concentration plus lithium chloride group (H + Li group), and a lithium chloride group (Li group) at gestational day 14. Rats received different concentrations of sevoflurane anesthesia for 2 h. The offspring rats were weaned at 28 days for behavioral testing (i.e., Morris Water Maze [MWM]), and fetal brains or postnatal hippocampal tissues were harvested for immunofluorescence staining, real-time PCR, and Western blotting analyses in order to determine the effect of sevoflurane exposure on NSC proliferation and the Wnt/β-catenin signaling pathway. Our results indicated that maternal exposure to 3.5% sevoflurane (H group) during the mid-gestational period impaired the performance of offspring rats in the MWM test, reduced NSC proliferation, and increased protein levels of fetal glycogen synthase kinase-3 beta (GSK-3β). Such treatment also decreased levels of β-catenin protein, CD44 RNA, and Cyclin D1 RNA relative to those observed in the C group. However, these effects were transiently attenuated by treatment with lithium chloride. Conversely, maternal exposure to 2% sevoflurane (L group) did not influence NSC proliferation or the Wnt signaling pathway. Our results suggest that sevoflurane exposure during the second trimester inhibits fetal NSC proliferation via the Wnt/β-catenin pathway and impairs postnatal learning and memory function in a dose-dependent manner.

Topics: Anesthetics, Inhalation; Animals; Cell Division; Cyclin D1; Dose-Response Relationship, Drug; Female; Fetus; Gestational Age; Glycogen Synthase Kinase 3 beta; Hippocampus; Hyaluronan Receptors; Learning Disabilities; Lithium Chloride; Maze Learning; Memory Disorders; Methyl Ethers; Nerve Tissue Proteins; Neural Stem Cells; Pregnancy; Prenatal Exposure Delayed Effects; Rats; Rats, Sprague-Dawley; Sevoflurane; Spatial Behavior; Wnt Signaling Pathway

Epilepsy is one of the serious neurological sequelae of bacterial meningitis. Rifampicin, the well-known broad spectrum antibiotic, is clinically used for chemoprophylaxis of meningitis. Besides its antibiotic effects, rifampicin has been proven to be an effective neuroprotective candidate in various experimental models of neurological diseases. In addition, rifampicin was found to have promising antioxidant, anti-inflammatory and anti-apoptotic effects. Herein, we investigated the anticonvulsant effect of rifampicin at experimental meningitis dose (20 mg/kg, i.p.) using lithium-pilocarpine model of status epilepticus (SE) in rats. Additionally, we studied the effect of rifampicin on seizure induced histopathological, neurochemical and behavioral abnormalities. Our study showed that rifampicin pretreatment attenuated seizure activity and the resulting hippocampal insults marked by hematoxylin and eosin. Markers of oxidative stress, neuroinflammation and apoptosis were evaluated, in the hippocampus, 24 h after SE induction. We found that rifampicin pretreatment suppressed oxidative stress as indicated by normalized malondialdehyde and glutathione levels. Rifampicin pretreatment attenuated SE-induced neuroinflammation and decreased the hippocampal expression of interleukin-1β, tumor necrosis factor-α, nuclear factor kappa-B, and cyclooxygenase-2. Moreover, rifampicin mitigated SE-induced neuronal apoptosis as indicated by fewer positive cytochrome c immunostained cells and lower caspase-3 activity in the hippocampus. Furthermore, Morris water maze testing at 7 days after SE induction showed that rifampicin pretreatment can improve cognitive dysfunction. Therefore, rifampicin, currently used in the management of meningitis, has a potential additional advantage of ameliorating its epileptic sequelae.

Topics: Animals; Apoptosis; Hippocampus; Inflammation; Lithium Chloride; Male; Memory Disorders; Oxidative Stress; Pilocarpine; Rats; Rats, Wistar; Rifampin; Seizures

Previous investigations have shown that NMDA receptors play an important role in learning and memory process. Lithium is a primary drug for management and prophylaxis of bipolar disorder. It can regulate signal transduction pathways in several regions of the brain and alter the function of several neurotransmitter systems involved in memory processes. The present study aimed to test the interaction of NMDA glutamatergic system of the CA1 region of dorsal hippocampus and lithium on spatial learning. Spatial memory was assessed in Morris water maze task by a single training session of eight trials followed by a probe trial and visible test 24h later. All drugs were injected into CA1 regions, 5min after training. Our data indicated that post- training administration of lithium (20μg/rat, intra-CA1) significantly impaired memory consolidation. Intra- CA1administration of NMDA, a glutamate receptor agonist (0.001 and 0.01μg/rat) showed spatial learning facilitation. Infusion of D-AP5, a glutamate receptor antagonist (0.05 and 0.1μg/rat) showed impairment of spatial memory. Our data also indicated that post- training administration of ineffective dose of NMDA (0.0001μg/rat) significantly decreased amnesia induced by lithium in spatial memory consolidation. In addition, post-training intra-CA1 injection of ineffective dose of D-AP5 (0.01μg/rat) could significantly increase lithium induced amnesia. It seems probable that signaling cascades of NMDA receptors that regulates synaptic plasticity are targets of anti-manic agents such as lithium. Our results suggest that NMDA receptors of the dorsal hippocampus may be involved in lithium-induced spatial learning impairment in the MWM task.

Topics: 2-Amino-5-phosphonovalerate; Animals; CA1 Region, Hippocampal; Catheters, Indwelling; Dose-Response Relationship, Drug; Lithium Chloride; Male; Memory Consolidation; Memory Disorders; N-Methylaspartate; Neuropsychological Tests; Nootropic Agents; Rats, Wistar; Receptors, N-Methyl-D-Aspartate; Spatial Learning; Spatial Memory

Recent studies suggest the importance of combined treatment of glycogen synthase kinase-3β (GSK-3β) and histone deacetylase (HDAC) inhibition in various in vitro and in vivo models of neurological diseases. Lithium chloride (LiCl) and valproate (VPA), two well-known mood stabilizers, have been reported to act through GSK-3β and HDAC inhibition, respectively. The present study was designed to investigate the potential of low-dose combination of LiCl and VPA in intracerebroventricular streptozotocin (ICV-STZ)-induced cognitive deficits in rats. STZ was injected twice (3 mg/kg ICV) on alternate days (day 1 and day 3) in rats. The ICV-STZ-treated rats received LiCl (60 mg/kg, i.p.), VPA (200 mg/kg, i.p.), and combination of both LiCl (60 mg/kg, i.p.) and VPA (200 mg/kg, i.p.) drugs for a period of 3 weeks. The ICV-STZ administration results in significant memory impairment, elevated oxidative-nitrosative stress, and reduced brain-derived neurotrophic factor (BDNF) levels. Using a battery of behavioral and biochemical tests, we observed that co-treatment of both drugs showed synergistic effect in improving the spatial learning and memory impairment as well as significantly attenuated the oxidative stress markers in STZ-treated rats as compared to either drug alone. Moreover, the combination of both drugs reversed the hyperinsulinemic brain condition and improved the BDNF levels in STZ-treated rats. Based upon these results, it could be suggested that a low-dose combination of LiCl and VPA produces synergistic and more consistent neuroprotective effects in ICV-STZ-induced cognitive deficits in rats.

Topics: Acetylcholinesterase; Animals; Avoidance Learning; Brain; Brain-Derived Neurotrophic Factor; Cognition Disorders; Drug Synergism; Drug Therapy, Combination; Glutathione; Glycogen Synthase Kinase 3; Histone Deacetylase Inhibitors; Insulin; Lithium Chloride; Malondialdehyde; Memory; Memory Disorders; Neuroprotective Agents; Nitrates; Nitrites; Rats, Wistar; Spatial Learning; Streptozocin; Valproic Acid

Lithium has been reported to have neuroprotective effects, but the preventive and treated role on cognition impairment and the underlying mechanisms have not been determined. In the present study, C57Bl/6 mice were subjected to repeated bilateral common carotid artery occlusion to induce the learning and memory deficits. 2 mmol/kg or 5 mmol/kg of lithium chloride (LiCl) was injected intraperitoneally per day before (for 7 days) or post (for 28 days) the operation. This repeated cerebral ischemia-reperfusion (IR) induced dynamic overexpression of ratio of Bcl-2/Bax and BDNF in hippocampus of mice. LiCl pretreatment and treatment significantly decreased the escape latency and increased the percentage of time that the mice spent in the target quadrant in Morris water maze. 2 mmol/kg LiCl evidently reversed the morphologic changes, up-regulated the survival neuron count and increased the BDNF gene and protein expression. 5 mmol/kg pre-LiCl significantly increased IR-stimulated reduce of Bcl-2/Bax and p-CREB/CREB. These results described suggest that pre-Li and Li treatment may induce a pronounced prevention on cognitive impairment. These effects may relay on the inhibition of apoptosis and increasing BDNF and p-CREB expression.

Topics: Animals; Apoptosis; bcl-2-Associated X Protein; Brain Ischemia; Brain-Derived Neurotrophic Factor; Carotid Artery Diseases; Cell Survival; Cyclic AMP Response Element-Binding Protein; Disease Models, Animal; Hippocampus; Learning Disabilities; Lithium Chloride; Male; Maze Learning; Memory Disorders; Mice, Inbred C57BL; Neurons; Nootropic Agents; Proto-Oncogene Proteins c-bcl-2; Random Allocation; Reperfusion Injury; Spatial Memory

Cocaine is thought to be addictive because it elevates dopamine levels in the striatum, reinforcing drug-seeking habits. Cocaine also elevates dopamine levels in the hippocampus, a structure involved in contextual conditioning as well as in reward function. Hippocampal dopamine promotes the late phase of consolidation of an aversive step-down avoidance memory. Here, we examined the role of hippocampal dopamine function in the persistence of the conditioned increase in preference for a cocaine-associated compartment. Blocking dorsal hippocampal D1-type receptors (D1Rs) but not D2-type receptors (D2Rs) 12 h after a single training trial extended persistence of the normally short-lived memory; conversely, a general and a specific phospholipase C-coupled D1R agonist (but not a D2R or adenylyl cyclase-coupled D1R agonist) decreased the persistence of the normally long-lived memory established by three-trial training. These effects of D1 agents were opposite to those previously established in a step-down avoidance task, and were here also found to be opposite to those in a lithium chloride-conditioned avoidance task. After returning to normal following cocaine injection, dopamine levels in the dorsal hippocampus were found elevated again at the time when dopamine antagonists and agonists were effective: between 13 and 17 h after cocaine injection. These findings confirm that, long after the making of a cocaine-place association, hippocampal activity modulates memory consolidation for that association via a dopamine-dependent mechanism. They suggest a dynamic role for dorsal hippocampal dopamine in this late-phase memory consolidation and, unexpectedly, differential roles for late consolidation of memories for places that induce approach or withdrawal because of a drug association.

Topics: Animals; Association Learning; Brain-Derived Neurotrophic Factor; Cocaine; Conditioning, Operant; Disease Models, Animal; Dopamine; Dopamine Agents; Dopamine Uptake Inhibitors; Dose-Response Relationship, Drug; Drug Administration Routes; Hippocampus; Lithium Chloride; Male; MAP Kinase Signaling System; Memory Disorders; Rats; Rats, Sprague-Dawley; Receptor, trkB; Time Factors

Hippocampal theta rhythm is believed to play a critical role in learning and memory. In animal models of temporal lobe epilepsy (TLE), there is evidence that alterations of hippocampal theta oscillations are involved in the cognitive impairments observed in this model. However, hippocampal theta frequency and amplitude at both the local field potential (LFP) and single unit level are strongly modulated by running speed, suggesting that the integration of locomotor information into memory processes may also be critical for hippocampal processing. Here, we investigate whether hippocampal speed-theta integration influences spatial memory and whether it could account for the memory deficits observed in TLE rats. LFPs were recorded in both Control (CTR) and TLE rats as they were trained in a spatial alternation task. TLE rats required more training sessions to perform the task at CTR levels. Both theta frequency and power were significantly lower in the TLE group. In addition, speed/theta frequency correlation coefficients and regression slopes varied from session to session and were worse in TLE. Importantly, there was a strong relationship between speed/theta frequency parameters and performance. Our analyses reveal that speed/theta frequency correlation with performance cannot merely be explained by the direct influence of speed on behavior. Therefore, variations in the coordination of theta frequency with speed may participate in learning and memory processes. Impairments of this function could explain at least partially memory deficits in epilepsy.

Topics: Animals; Disease Models, Animal; Electrodes, Implanted; Electroencephalography; Epilepsy, Temporal Lobe; Food Deprivation; Hippocampus; Lithium Chloride; Maze Learning; Memory Disorders; Muscarinic Agonists; Pilocarpine; Rats; Rats, Sprague-Dawley; Space Perception; Theta Rhythm; Time Factors

Transcranial direct current stimulation (tDCS) is a recently available, noninvasive brain stimulation technique. The effects of cathodal tDCS on convulsions and spatial memory after status epilepticus (SE) in immature animals were investigated.. Rats underwent lithium-pilocarpine-induced SE at postnatal day (P) 20-21 and received daily 30-min cathodal tDCS for 2 weeks at P23-36 through a unilateral epicranial electrode at 200μA. After tDCS, convulsions over 2 weeks were estimated by 20-h/day video monitoring. The rats were tested in a water maze for spatial learning at P50-53 and the brains were examined for cell loss and mossy fiber sprouting.. Long-term treatment with weak cathodal tDCS reduced SE-induced hippocampal cell loss, supragranular and CA3 mossy fiber sprouting, and convulsions (reduction of 21%) in immature rats. The tDCS treatment also rescued cognitive impairment following SE.. These findings suggested that cathodal tDCS has neuroprotective effects on the immature rat hippocampus after pilocarpine-induced SE, including reduced sprouting and subsequent improvements in cognitive performance. Such treatment might also have an antiepileptic effect.

Topics: Animals; Disease Models, Animal; Electric Stimulation Therapy; Hippocampus; Lithium Chloride; Male; Maze Learning; Memory Disorders; Mossy Fibers, Hippocampal; Nerve Degeneration; Pilocarpine; Rats; Rats, Wistar; Seizures; Status Epilepticus

The glycogen synthase kinase-3β (GSK3β) pathway plays a central role in Alzheimer's disease (AD) and its deregulation accounts for many of the pathological hallmarks of AD. Lithium, which modulates GSK3β activity, has been shown to reduce amyloid production and tau phosphorylation in pre-pathological AD mouse models. In this study, we investigated the effects of chronic LiCl treatment in aged double transgenic mice (AβPPSwe/PS1A246E). We found that chronic lithium treatment decreased the γ-cleavage of amyloid-β protein precursor, further reduced amyloid-β production and senile plaque formation, accompanied by the improvement in spatial learning and memory abilities. Because autophagy may play an important role in the pathology of AD, we also assessed the autophagy activity and found that the chronic lithium treatment attenuated the autophagy activation in this AD mouse model. Our results suggest that prolonged lithium treatment, even during the later stages of AD, could be an effective therapeutics.

Topics: Aging; Alzheimer Disease; Amyloid beta-Peptides; Animals; Disease Models, Animal; Down-Regulation; Female; Glycogen Synthase Kinase 3; Lithium Chloride; Memory Disorders; Mice; Mice, Transgenic; Time Factors; Treatment Outcome

Postoperative cognition impairment is a perishing complication in elderly patients undergone surgeries. Lithium is widely used in psychiatric patients for its role in neuronal protection, whereas whether or not it could attenuate surgery-associated postoperative cognition dysfunction used prophylactically is not well defined. After approval by the Institutional Animal Care and Use Committee, 48 male Sprague-Dawley rats aged 18months old were randomly divided into three groups with 16 each: i, no surgeries and drugs were given; ii, surgical procedures were performed only without drug delivery; iii, prophylactic 2mM/kg lithium chloride was given intraperitoneally once a day for seven days before surgeries. The change in spatial memory was assessed with Morris Water Maze (MWM), and the activation of PI3K/AKT/mTOR pathway was detected, and the levels of hippocampal glycogen synthase kinase-3β (p-GSK-3β) phosphorylation at serine 9 and interleukin-1β (IL-1β) were measured. The MWM detection showed that both swimming latency and distance were considerably prolonged by the surgeries, but these changes could be markedly shortened by prophylactic lithium administration. Meanwhile, the changes in the hippocampal PI3K cascades and p-GSK-3β and IL-1β expression displayed corresponding changes that were parallel to the alterations of spatial memory, and inhibition of PI3K and GSK-3β suggested upstream PI3K activation leads to downstream change in p-GSK-3β and IL-1β. These results indicate, at least in part, that prophylactic lithium can alleviate surgery-associated impairment of the spatial memory in aged rats which is strongly associated with the reduced levels of hippocampal p-GSK-3β and IL-1β resulted from the activation of PI3K/AKT/mTORC2 pathway.

Topics: Aging; Animals; Cognition; Glycogen Synthase Kinase 3; Glycogen Synthase Kinase 3 beta; Hippocampus; Injections, Intraperitoneal; Interleukin-1beta; Lithium Chloride; Male; Memory Disorders; Neuroprotective Agents; Phosphorylation; Postoperative Complications; Primary Prevention; Rats; Rats, Sprague-Dawley; Surgical Procedures, Operative

The medial prefrontal cortex (mPFC) is a brain area crucial for memory, attention, and decision making. Specifically, the noradrenergic system in this cortex is involved in aversive learning, as well as in the retrieval of these memories. Some evidence suggests that this area has an important role during taste memory, particularly during conditioned taste aversion (CTA), a model of aversive memory. Despite some previous evidence, there is scarce information about the role of adrenergic receptors in the mPFC during formation of aversive taste memory and appetitive/incidental taste memory. The goal of this research was to evaluate the role of mPFC beta-adrenergic receptors during CTA acquisition/consolidation or CTA retrieval, as well as during incidental taste memory formation using the model of latent inhibition of CTA. The results showed that infusions in the mPFC of the beta-adrenergic antagonist propranolol before CTA acquisition impaired both short- and long-term aversive taste memory formation, and also that propranolol infusions before the memory test impaired CTA retrieval. However, propranolol infusions before pre-exposure to the taste during the latent inhibition procedure had no effect on incidental taste memory acquisition or consolidation. These data indicate that beta-adrenergic receptors in the mPFC have different functions during taste memory formation: they have an important role during aversive taste association as well as during aversive retrieval but not during incidental taste memory formation.

Topics: Adrenergic beta-Antagonists; Animals; Appetitive Behavior; Avoidance Learning; Conditioning, Classical; Lithium Chloride; Male; Memory Disorders; Memory, Long-Term; Memory, Short-Term; Mental Recall; Prefrontal Cortex; Propranolol; Rats; Rats, Sprague-Dawley; Receptors, Adrenergic, beta; Saccharin; Taste Perception

1. Postoperative cognitive dysfunction has become more prevalent in recent years. We used a splenectomized rat model with postoperative spatial learning and memory deficits to investigate the role of tau hyperphosphorylation and glycogen synthase kinase-3β (GSK-3β) within the hippocampus. 2. Cognitive function was assessed in a Y-maze 1 day before and 1, 3 and 7 days after surgery. We measured site-specific phosphorylation of hippocampal tau (Thr-205 and Ser-396), GSK-3β activity and expression of interleukin-1β (IL-1β), tumour necrosis factor-α (TNF-α) mRNA and protein as markers of inflammation. We also tested the effects of treatment with lithium chloride (LiCl), a GSK-3β inhibitor. 3. Splenectomy was associated with learning and memory impairment 3 days later, as well as a rapid and massive hyperphosphorylation of hippocampal tau at Thr-205 and Ser-396, activated GSK-3β, and increased IL-1β and TNF-α expression. LiCl completely restored tau hyperphosphorylation to control levels. 4. These data from the splenectomized rat model suggest that inflammatory factors affect tau pathology through the GSK-3β signalling pathway and that LiCl is a promising treatment for postoperative cognitive deficits.

Topics: Animals; Biomarkers; Glycogen Synthase Kinase 3; Glycogen Synthase Kinase 3 beta; Inflammation Mediators; Lithium Chloride; Male; Maze Learning; Memory Disorders; Neuroprotective Agents; Phosphorylation; Postoperative Complications; Rats; Rats, Sprague-Dawley; Signal Transduction; Splenectomy; tau Proteins; Treatment Outcome

Rats use time-of-day cues to modulate learned taste aversion memories. If adult rats are accustomed to drinking saline in the evening and they receive a lithium chloride injection after drinking saline in the morning, they form a stronger aversion to saline than rats that were conditioned after drinking saline at the familiar time. The difference indicated that the rats formed segregated representations of saline taste and the time of day the saline was consumed. This was inferred because the modulation of learning by time of day was observed when the aversions were tested at the familiar evening drinking time. If the rats had formed a compound representation of saline taste and the time of day it was consumed, the opposite pattern of differences would be expected. We used this modulation of learning by time of day to assay whether aged rats have an impaired ability to form segregated representations of experience. We find that aged rats had similar saline aversions if they were conditioned at either the familiar or the unfamiliar time of day. Furthermore, dorsal hippocampal lesions affecting also the overlying parietal cortex in the aged rats caused greater saline aversions if the rats were conditioned after drinking saline at the familiar time of day. This indicated that aged rats are aware of the time of day but after the lesion, they act as if they do not segregate saline taste from the time of day it was consumed. The results suggest that the ability to form segregated representations of a complex experience is impaired in aging and abolished by hippocampal lesions.

Topics: Aging; Animals; Antimanic Agents; Avoidance Learning; Conditioning, Psychological; Denervation; Hippocampus; Learning; Lithium Chloride; Male; Memory; Memory Disorders; Parietal Lobe; Rats; Rats, Wistar; Time Perception

The effects of systemic treatment with lipopolysaccharide (LPS) on conditioned gaping in a rodent model of anticipatory nausea were examined. Stimulation of the immune system has been found to enhance, impair, or have no effect on various learning and memory tasks. The development of anticipatory nausea is formed through a classically conditioned response to a context that has been paired previously with toxin-induced nausea and/or vomiting. Rats display a distinctive conditioned gaping response when injected with a nausea-inducing drug such as LiCl. In the present study, male Long-Evans rats were injected intraperitoneally with LPS (200microg/kg) or saline (NaCl) followed 90min later by an injection of the toxin LiCl or saline before being placed in a distinctive context on four conditioning days (72h apart). On the condition test day, rats (n=6/group) were placed in the distinctive context in a drug-free state and behavioral responses were videotaped. Rats given LPS followed by LiCl were found to have significantly fewer gaping responses when compared to rats given NaCl followed by LiCl. All groups were also found to have similar levels of spontaneous ingestive behaviors suggesting that the decrease in gaping was not due to motor impairment. The present results suggest that activation of the immune system with LPS administration significantly impairs the acquisition of anticipatory nausea.

Topics: Animals; Association Learning; Conditioning, Psychological; Disease Models, Animal; Immune System Phenomena; Lipopolysaccharides; Lithium Chloride; Male; Memory; Memory Disorders; Nausea; Pons; Rats; Rats, Long-Evans; Vomiting, Anticipatory

In the present study, effects of intracerebroventricular (i.c.v.) injections of mu-opioid receptor agonist and antagonist on lithium state-dependency were investigated. For memory assessment, a one-trial step-down inhibitory avoidance task was used in adult male NMRI mice. Intraperitoneal (i.p.) administration of lithium (10 mg/kg) after training impaired memory when retrieval was tested 24 h later. The memory impairment was reversed by pretest administration of the same dose of lithium, suggesting state-dependency induced by lithium. In addition, i.c.v. administration of both lithium (2 and 4 microg/mouse, i.c.v.) and morphine (3 and 6 microg/mouse, i.c.v.) before the test reversed memory impairment induced by post-training lithium (10 mg/kg, i.p.). On the other hand, pretest administration of naloxone (1 and 2 mg/kg) which had no effects alone on inhibitory avoidance response, prevented the improving effects of both morphine (3 microg/mouse, i.c.v.) and lithium (2 microg/mouse, i.c.v.) on memory retrieval. The results suggest that the mu-opioid receptors in the central nervous system may be involved in the retrieval of lithium state-dependent learning.

Topics: Animals; Antimanic Agents; Avoidance Learning; Lithium Chloride; Male; Memory Disorders; Mice; Morphine; Naloxone; Receptors, Opioid, mu

To explore the mechanism of tau hyperphosphorylation and the effect of LiCl on tau phosphorylation and the memory retention deficits in streptozotocin-induced diabetes mellitus (DM) rats.. The rats were randomly divided into control, DM, DM + NaCl, and DM + LiCl groups and diabetes was induced by streptozotocin. The activity of glycogen synthase kinase-3 (GSK-3) was measured by 32P-labelling. The level of tau phosphorylated and changes of memory retention were examined by Western blotting and step down test, respectively.. Compared with control group, the activity of GSK-3 and tau phosphorylation was increased, and the memory retention was impaired in DM group. When the rats were treated with LiCl, the activity of GSK-3 and hyperphosphorylation of tau were significantly arrested (P < 0.05, P < 0.01), and the memory retention deficit was significantly improved (P < 0.05).. The hyperphosphorylation of tau can be induced by activation of GSK-3 in diabetic rats. Lithium protects tau from hyperphosphorylation and may rescue memory retention in the rats by inhibiting GSK-3 activity.

Topics: Animals; Cerebral Cortex; Diabetes Mellitus, Experimental; Glycogen Synthase Kinase 3; Lithium Chloride; Male; Memory Disorders; Phosphorylation; Rats; Rats, Sprague-Dawley; tau Proteins