Uncovering the protective potential of vanillic acid against traumatic brain injury-induced cognitive decline in male rats: Insights into underlying mechanisms.

Traumatic brain injury (TBI) is a significant contributor to global mortality and disability, and there is still no specific drug available to treat cognitive deficits in survivors. Vanillic acid (VA), a bioactive phenolic compound, has shown protective effects in various models of neurodegeneration; however, its impact on TBI outcomes remains elusive. Therefore, this study aimed to elucidate the possible role of VA in ameliorating TBI-induced cognitive decline and to reveal the mechanisms involved. TBI was induced using the Marmarou impact acceleration model to deliver an impact force of 300 g, and treatment with VA (50 mg/kg; P.O.) was initiated 30 minutes post-TBI. The cognitive performance, hippocampal long-term potentiation (LTP), oxidative stress markers, neurological function, cerebral edema, and morphological changes were assessed at scheduled points in time. TBI resulted in cognitive decline in the passive avoidance task, impaired LTP in the perforant path-dentate gyrus (PP-DG) pathway, increased hippocampal oxidative stress, cerebral edema, neurological deficits, and neuronal loss in the rat hippocampus. In contrast, acute VA administration mitigated all the aforementioned TBI outcomes. The data suggest that reducing synaptic plasticity impairment, regulating oxidative and antioxidant defense, alleviating cerebral edema, and preventing neuronal loss by VA can be at least partially attributed to its protection against TBI-induced cognitive decline.

Early-life manipulation of the serotonergic system exacerbates the harmful effects of sleep deprivation on cognitive functions.

Serotonin is a monoamine neurotransmitter that plays a main role in regulating physiological and cognitive functions. Serotonergic system dysfunction is involved in the etiology of various psychiatric and neurological disorders. Therefore, the present study was designed to investigate the effects of early-life serotonin depletion on cognitive disorders caused by sleep deprivation. Serotonin was depleted by para-chlorophenylalanine (PCPA, 100 mg/kg, s.c.) at postnatal days 10-20, followed by sleep deprivation-induced through the multiple platform apparatus for 24 h at PND 60. After the examination of the novel object recognition and passive avoidance memories, the hippocampi and prefrontal cortex were dissected to examine the brain-derived neurotrophic factor (BDNF) mRNA expression by PCR. Our findings showed that postnatal serotonin depletion and sleep deprivation impaired the novel object recognition and passive avoidance memories and changed the BDNF levels. In the same way, the serotonin depletion in early life before sleep deprivation exacerbated the harmful effects of sleep deprivation on cognitive function and BDNF levels. It can be claimed that the serotonergic system plays a main role in the modulation of sleep and cognitive functions.

Multifactorial effects of short duration early exposure low intensity magnetic field stimulation in Streptozotocin induced Alzheimer's disease rat model.

Alzheimer's disease (AD) is an approaching, progressive public health crisis which presently lacks an effective treatment. Various non-invasive novel therapies like repetitive transcranial magnetic stimulation have shown potential to improve cognitive performance in AD patients. In the present study, the effect of extremely low intensity magnetic field (MF) stimulation on neurogenesis and cortical electrical activity was explored. Adult Wistar rats were divided into Sham, AD and AD + MF groups. Streptozotocin (STZ) was injected intracerebroventricularly, at a dose of 3 mg/kg body weight for developing AD model. The AD rats were then exposed to MF (17.96 µT) from 8th day of STZ treatment until 15th day, followed by cognitive assessments and electrocortical recording. In brain tissue samples, cresyl violet staining and BrdU immunohistochemistry were done. MF exposure, improved passive avoidance and recognition memory, attenuated neuronal degeneration and enhanced cell proliferation (BrdU positive cells) in comparison to AD rats. It also significantly restores delta wave power from frontal lobe. Our results suggest that early-stage MF exposure could be an asset for AD research and open new avenues in slowing down the progression of Alzheimer's disease.

Protective effects of selegiline against amyloid beta-induced anxiety-like behavior and memory impairment.

BACKGROUND: Alzheimer's disease (AD) is a complex and common neurodegenerative disorder. The present study aimed to investigate the potential effects of selegiline (SEL) on various aspects of memory performance, anxiety, and oxidative stress in an AD rat model induced by intracerebroventricular injection of amyloid beta1-42 (Aß1-42). METHODS: Oral administration of SEL at a dose of 0.5 mg/kg/day was performed for 30 consecutive days. Following the 30 days, several tests, including the open-field, elevated plus-maze, novel object recognition, Morris water maze, and passive avoidance learning were conducted to assess locomotor activity, anxiety-like behavior, recognition memory, spatial memory, and passive avoidance memory, respectively. RESULTS: The results indicate that the induction of AD in rats led to recognition memory, spatial memory, and passive avoidance memory impairments, as well as increased anxiety. Additionally, the AD rats exhibited a decrease in total antioxidant capacity and an increase in total oxidant status levels, suggesting an imbalance in oxidative-antioxidant status. However, the administration of SEL improved memory performance, reduced anxiety, and modulated oxidative-antioxidant status in AD rats. CONCLUSIONS: These findings provide evidence that SEL may alleviate anxiety-like behavior and cognitive deficits induced by Aß through modulation of oxidative-antioxidant status.

Cacao consumption improves passive avoidance memory impairment in a rat model of Alzheimer's disease: the role of hippocampal synaptic plasticity and oxidative stress.

Introduction: Alzheimer's disease (AD) causes progressive loss of cognitive function and synaptic plasticity, which is the most common form of dementia. The present study was designed to scrutinize the effects of cacao on passive avoidance memory function and to identify the roles of hippocampal synaptic plasticity and oxidative stress in an AD rat model induced by unilateral intracerebroventricular (UICV) injection of amyloid-beta (Aß). Methods: Oral administration of cacao (500 mg/kg/ day) was given for 2 consecutive months. A memory retention test was conducted 24 h after passive avoidance training was completed. Subsequently, the amplitude of population spike (PS) and slope of field excitatory postsynaptic potentials (fEPSPs) were assessed at hippocampal long-term potentiation (LTP) in perforant pathway-dentate gyrus (PP-DG) synapses. Moreover, total thiol group (TTG) and malondialdehyde (MDA) concentrations were evaluated in the plasma. Furthermore, compact Aß plaques were detected in the hippocampal DG by performing Congo red staining. Results: As a result of AD induction, passive avoidance memory was impaired; also, reduced fEPSP slopes, PS amplitudes, and content of TTG, and increase in MDA levels in the rats were observed. In contrast, cacao treatment ameliorated passive avoidance memory impairment, improved hippocampal LTP impairment, modulated oxidative-antioxidative status, and delayed Aß plaques production in AD rats. Disscussion: Conclusively, cacao alleviates Aß-induced cognitive deficit, probably by the amelioration of hippocampal LTP impairment, modulation of oxidative-antioxidative status, and inhibition of Aß plaque accumulation.

Interaction effect of crocin and citalopram on memory and locomotor activity in rats: an insight into BDNF and synaptophysin levels in the hippocampus.

Selective serotonin reuptake inhibitors (SSRIs) are widely used drugs for the treatment of depression. Citalopram is one of the most prescribed SSRIs that is useful for the treatment of depression, obsessive-compulsive disorder, and anxiety disorders. On the other hand, crocin (active constitute of saffron) has pro-cognitive and mood enhancer effects. Also, both citalopram and crocin affect the function and expression of brain-derived neurotrophic factor (BDNF) and synaptophysin, two molecular factors that are involved in cognitive functions and mood. In the present study, we aim to investigate the interaction effect of citalopram and crocin on rats' performance in the open field test (locomotor activity and anxiety-like behavior) and the shuttle box (passive avoidance memory). Citalopram was injected at the doses of 10, 30, and 50 mg/kg, and crocin was injected at the dose of 50 mg/kg; all administrations were intraperitoneal. Real-time PCR was used to assess the expression level of BDNF and synaptophysin in the hippocampus. The results showed that citalopram (30 and 50 mg/kg) impaired passive avoidance memory and decreased BDNF and synaptophysin expression in the hippocampus, while crocin reversed memory impairment, and BDNF and synaptophysin expression in the hippocampus of rats received citalopram 30 mg/kg. Also, crocin partially showed these effects in rats that received citalopram 50 mg/kg. The results of the open field test were unchanged. In conclusion, we suggested that BDNF and synaptophysin may be involved in the effects of both citalopram and crocin.

Persistent diazinon induced neurotoxicity: The effect on inhibitory avoidance memory performance, amyloid precursor proteins, and TNF-α levels in the prefrontal cortex of rats.

INTRODUCTION: Organophosphate pesticides (Ops) like diazinon (DZN) have well-known neurotoxic effects and low-level chronic exposure has been linked to detrimental neurobehavioral impairments and memory deficits. However, it's not entirely clear how DZN-induced biological changes, particularly in the prefrontal cortex (PFC) contribute to these effects. The purpose of this study is to investigate the impact of DZN exposure on inhibitory avoidance (IA) memory function, amyloid precursor expression (APP), and proinflammatory tumor necrosis factor-α (TNF-α) levels in the rat cortex. MATERIALS AND METHODS: Rats were divided into 4 groups and recived 2 mg/kg DZN for 5-days or 12-weeks and two control groups recived the same volume of vehicle. IA memory was assesed using the shuttle box apparatus. Rats were sacrificed and the prefrontal cortex PFC were removed. Real-time PCR and Western blotting were used to messure TNF-α, and amyloid protein precursors gene expression and protein levels. RESULTS: Our findings indicated that DZN caused body weight loss and a notable decline in performance on the IA memory. Additionally, 5-days exposure increased APP and APLP2 protein levels in the PFC, while 12-weeks exposure decreased these levels. Furthermore, expression of APP and APLP2 gens were decreased in PFC. TNF-α levels increased as a result of 5-days exposure to DZN, but these levels dropped to normal after 12-weeks administration, and this observation was significant. CONCLUSION: Taken together, exposure to low doses of DZN leads to disturbances in IA memory performance and also alternations in amyloid beta precursors that can be related to increased risk of Alzheimer's disease.

Berberine improves inhibitory avoidance memory impairment of Toxoplasma gondii-infected rat model of ketamine-induced schizophrenia.

BACKGROUND: Memory impairment caused by Toxoplasma gondii infection has been documented. Berberine (BRB) is well known for its enhancing effects on memory and has shown promising results. However, the impact of BRB on T. gondii infection and schizophrenia-induced consolidation and reconsolidation memory impairment is still unclear. Here; we examined the effect of BRB on the inhibitory avoidance (IA) memory consolidation and reconsolidation impairment induced by T. gondii infection, and ketamine (Ket) as a pharmacological model of schizophrenia. Also; the brain-derived neurotrophic factor (BDNF) levels in the medial prefrontal cortex (mPFC) and hippocampus were analyzed. METHODS: Rats were infected with T. gondii RH strain or received Ket (30 mg/kg/day) intraperitoneally (i.p) for at least five consecutive days (as the model of schizophrenia). Then followed by oral administration with BRB (25 mg/kg/day) for five days. Finally, the IA memory retention test was examined 48 post-conditioning, and BDNF was measured. RESULTS: Results indicated IA memory impairment in T. gondii-infected animals since lower step-through latency (STL) was observed than in control animals. We found significant (P = 0.01, P = 0.001) elevations in STL and a significant decrease (P = 0.001) in total time spent in the dark area following BRB administration in infected and Ket-treated rats, indicating improvement (increased STL) in consolidation and reconsolidation memory. Moreover, BDNF levels were reduced (P = 0.01) in the hippocampus and mPFC regions of both T. gondii- infected and Ket-induced groups, which remarkably enhanced after BRB treatment. Furthermore; we found that BRB administration notably increased the mPFC BDNF levels in mPFC (P < 0.01) and hippocampus (P = 0.001) in the Ket-treated and rats infected with T. gondii. CONCLUSION: Taken together; BRB may be a valuable preclinical treatment for improving memory impairment through BDNF expression in PFC and hippocampus, therefore; BRB is suggested for memory disturbances induced by T. gondii infection.

Silymarin pretreatment protects against ethanol-induced memory impairment: Biochemical and histopathological evidence.

BACKGROUND: Ethanol (Eth.) abuse induces memory impairment. Oxidative damage and apoptosis are considered the likely causes of memory impairment. Silymarin (Sil.) is a flavonoid isolated from the plant Silymarin marianum (milk thistle). While studies have reported the neuroprotective effect of Sil. against neurodegenerative processes, the precise mechanism of action of Sil. in Eth.-induced memory impairment remains unclear. METHODS: Twenty-eight rats were equally divided into four groups: Control (saline 1 ml/rat); Sil. (200 mg/kg for 30 days); Eth. (2 g/kg/day for 30 days); and Sil. + Eth. Behavioral tests including inhibitory avoidance and open field were used to investigate memory and locomotion. Brain antioxidant parameters, including catalase, superoxide dismutase, total antioxidant capacity and total thiol group, plus oxidative parameters, including malondialdehyde and total oxidant status, followed by hippocampal apoptosis (Bax/Bcl2, cleaved caspase) and histopathological changes were evaluated in the groups. RESULTS: While the administration of Eth. impaired memory, Sil. significantly reversed Eth-induced memory deficits. Eth. administration also augmented brain oxidative and hippocampal apoptosis parameters. In contrast, a marked reduction in brain antioxidant and anti-apoptotic parameters was observed in the Eth. group. At the tissue level, hippocampal sections from Eth.-treated animals revealed severe neuronal damage. The administration of Sil. to Eth.-treated rats remarkably alleviated all the said Eth.-induced biochemical and histopathological effects. On the contrary, Sil. alone did not change the behavior and biochemical/molecular parameters. CONCLUSION: The memory-enhancing effect of Sil. in Eth.-induced demented rats may be partly mediated by the augmented antioxidant effects and amelioration of apoptotic and histopathological changes.

Geraniol improves passive avoidance memory and hippocampal synaptic plasticity deficits in a rat model of Alzheimer's disease.

Alzheimer's disease (AD) is the most progressive and irreversible neurodegenerative disease that leads to synaptic loss and cognitive decline. The present study was designed to evaluate the effects of geraniol (GR), a valuable acyclic monoterpene alcohol, with protective and therapeutic effects, on passive avoidance memory, hippocampal synaptic plasticity, and amyloid-beta (Aß) plaques formation in an AD rat model induced by intracerebroventricular (ICV) microinjection of Aß1-40. Seventy male Wistar rats were randomly into sham, control, control-GR (100 mg/kg; P.O. (orally), AD, GR-AD (100 mg/kg; P.O.; pretreatment), AD-GR (100 mg/kg; P.O.; treatment), and GR-AD-GR (100 mg/kg; P.O.; pretreatment & treatment). Administration of GR was continued for four consecutive weeks. Training for the passive avoidance test was carried out on the 36th day and a memory retention test was performed 24 h later. On day 38, hippocampal synaptic plasticity (long-term potentiation; LTP) was recorded in perforant path-dentate gyrus (PP-DG) synapses to assess field excitatory postsynaptic potentials (fEPSPs) slope and population spike (PS) amplitude. Subsequently, Aß plaques were identified in the hippocampus by Congo red staining. The results showed that Aß microinjection increased passive avoidance memory impairment, suppressed of hippocampal LTP induction, and enhanced of Aß plaque formation in the hippocampus. Interestingly, oral administration of GR improved passive avoidance memory deficit, ameliorated hippocampal LTP impairment, and reduced Aß plaque accumulation in the Aß-infused rats. The results suggest that GR mitigates Aß-induced passive avoidance memory impairment, possibly through alleviation of hippocampal synaptic dysfunction and inhibition of Aß plaque formation.

Curcumin attenuates memory impairments and long-term potentiation deficits by damping hippocampal inflammatory cytokines in lipopolysaccharide-challenged rats.

Neuroinflammation is a key pathological event triggering neurodegenerative process, resulting in neurologic sequelae. Curcumin (cur) has recently received increasing attention due to its anti-inflammatory properties. Therefore, we investigated the protective effects of curcumin on lipopolysaccharide (LPS)-induced memory impairments, long-term potentiation (LTP) deficits, hippocampal inflammatory cytokines, and neuronal loss in male rats. Rats were randomly divided into four groups as follows: (1) Vehicle; (2) cur; (3) LPS; and (4) cur/LPS. Following curcumin pretreatment (50 mg/kg, per oral via gavage, 14 consecutive days), animals received a single dose of LPS (1 mg/kg, intraperitoneally) or saline. Twenty-four hours after LPS/or saline administration, passive avoidance test (PAT), hippocampal LTP, inflammatory cytokines (TNFα, IL-1ß), and neuronal loss were assessed in hippocampal tissue of rats. Our results indicated that pretreatment with curcumin in LPS-challenged rats attenuates memory impairment in PAT, which was accompanied by significant increase in the field excitatory post-synaptic potential (fEPSP) slope and population spike (PS) amplitude. Hence, pretreatment with curcumin in LPS-treated rats decreased hippocampal concentration of tumor necrosis factor-alpha (TNF-α) and interleukin-1ß (IL-1ß), as well as reduced neuronal loss in the hippocampal tissue. This study provide evidence that pretreatment with curcumin attenuates LPS-induced memory impairment and LTP deficiency, which may be partly related to the amelioration of inflammatory cytokines and neuronal loss in the hippocampal tissue.

Minocycline attenuates cholinergic dysfunction and neuro-inflammation-mediated cognitive impairment in scopolamine-induced Alzheimer's rat model.

OBJECTIVE: Minocycline, a semisynthetic tetracycline-derived antibiotic, has various pharmacological effect such as anti-inflammatory, anti-oxidative stress, and anti-apoptotic effects. The current study investigated the involvement of neuro-inflammatory, oxidative stress, and cholinergic markers in neuroprotection by minocycline against scopolamine-induced brain damage. METHODS: Minocycline was administered (oral, 10, 15, and 30 mg/kg, daily) to groups of amnesic rats for 21 days. Passive avoidance memory and spatial learning and memory were assessed. Following that, oxidative stress, cholinergic function, and neuro-inflammation markers were evaluated in the brain tissue. RESULTS: According to our biochemical data, treatment of the scopolamine-injured rats with minocycline decreased the levels of malondialdehyde and acetylcholinesterase (AChE) as well as mRNA expression of AChE and neuro-inflammation markers (tumor necrosis factor-α, interleukin (IL)-1ß, IL-6). It also increased the total thiol levels and superoxide dismutase activity as well as mRNA expression of cholinergic receptor M1 (ChRM1). Moreover, minocycline modified distance and latencies in Morris water maze, prolonged latency to enter the black zone and light time while decreasing time spent and frequency of entries to darkness. CONCLUSION: Taken together, the data indicate that treatment with minocycline improved memory dysfunction mediated possibly through restoring AChE and ChRM1 levels, oxidant/antioxidant balance, as well as inhibiting inflammatory responses.

Therapeutic effects of saffron extract on different memory types, anxiety, and hippocampal BDNF and TNF-α gene expressions in sub-chronically stressed rats.

Objective: While stress reportedly impairs memory, saffron enhances it. This study investigated the therapeutic effects of saffron extract on different memory types, anxiety-like behavior, and expressions of BDNF and TNF-α genes in sub-chronically stressed rats.Methods: Rats were randomly assigned to control, restraint stress (6 h/day/7 days), two 7-days saffron treatments with 30 and 60 mg/kg, and two stress-saffron groups (30 and 60 mg/kg/7 post-stress days). Serum cortisol level and hippocampal BDNF and TNF-α gene expressions were measured. Open field, passive avoidance, novel object recognition, and object location tests were performed to assess anxiety-like behavior and avoidance as well as cognitive and spatial memories, respectively.Results: The low saffron dose in the sub-chronic stressed group led to a significant increase in passive avoidance latency from day 3 onward whereas this effect was observed after 7 days under the high-dose treatment that simultaneously led to a significant decline in serum cortisol level. While the low saffron dose led to a sharp drop in hippocampal TNF-α gene expression, the high dose significantly increased the hippocampal BDNF gene expression in the sub-chronic stress group. Finally, both saffron doses reduced anxiety in the stressed groups.Conclusion: Compared to the low saffron dose, the high dose had a latent but long-lasting impact. Cognitive and spatial memories remained unaffected by either stress or saffron treatment. In addition, only the high saffron dose reversed anxiety in the sub-chronically stressed group. These findings suggest that various doses of saffron act differently on different brain functions under sub-chronic stress conditions.Abbreviations: Brain derived neurotrophic factor (BDNF), tumor necrosis factor-α (TNF-α), hypothalamic-pituitary-adrenal axis (HPA), novel object recognition task (NORT), novel object location task (NOLT), open field test (OFT), passive avoidance (PA).

The bidirectional effect of prelimbic 5-hydroxytryptamine type-4 (5-HT4) receptors on ACPA-mediated aversive memory impairment in adult male Sprague-Dawley rats.

OBJECTIVES: This study aimed at investigating the effect of serotonergic 5-HT4 receptor agonist/antagonist on memory consolidation deficit induced by ACPA (a potent, selective CB1 cannabinoid receptor agonist) in the pre-limbic (PL) cortex. MATERIALS AND METHODS: We used the step-through passive avoidance test to evaluate memory consolidation of male Sprague-Dawley (SD) rats. Bilateral post-training microinjections of the drugs were done in a volume of 0.6 µl/rat into the PL area (0.3 µl per side). RESULTS: The results showed a significant interaction between RS67333 hydrochloride (5-HT4 receptor agonist) or RS23597-190 hydrochloride (5-HT4 receptor antagonist) and ACPA on consolidation of aversive memory. RS67333 hydrochloride (0.5 µg/rat) enhanced consolidation of memory and its co-administration at the ineffective dose of 0.005 µg/rat with ineffective (0.001 µg/rat) or effective (0.1 µg/rat) doses of ACPA improved and prevented impairment of memory caused by ACPA, respectively. In other words, RS67333 had a bidirectional effect on ACPA-caused amnesia. While RS23597-190 hydrochloride had no effect on memory at the doses used (0.005, 0.01, 0.1, or 0.5 µg/rat); but its concomitant use with an effective dose of ACPA (0.1 µg/rat) potentiated amnesia. None of the drugs had an effect on locomotor activity. CONCLUSION: This study revealed that activation or deactivation of the 5-HT4 receptors in the PL may mediate the IA memory impairment induced by ACPA indicating a modulatory role for the 5-HT4 serotonergic receptors.

Association between nandrolone and behavioral alterations: A systematic review of preclinical studies.

BACKGROUND AND AIM: In recent years the expanding misuse of Nandrolone among non-athletes, particularly adolescent males is a prevalent global concern due to its adverse effects. This article provides a summary of the experimental studies to clarify the relationship between Nandrolone exposure and behavioral and cognitive performances. MATERIALS AND METHODS: The present systematic review was conducted using PubMed, Embase and ScienceDirect databases, from 2000 to 2020, using the following key terms: Nandrolone AND Cognition, Nandrolone AND Learning, Nandrolone AND Memory, Nandrolone AND (Synaptic plasticity or Hippocampal synaptic plasticity), Nandrolone AND (Aggression or Aggressive-like behavior), Nandrolone AND (Anxiety or Anxiety-like behavior), Nandrolone AND (Depression or Depressive-like behavior). RESULTS: 33 qualified papers were selected from the 2498 sources found. Of the 33 cases, 32 (96.97%) were males while only 1 (3.03%) was female and male. From 33 selected articles 8 reported studies were related to spatial memory, 2 reported studies were related to avoidance memory, 11 studies reported information on synaptic plasticity, 11 reported studies were related to aggressive behavior, 8 reported studies were related to aggressive behavior and 6 reported studies were related to depression. CONCLUSION: Nandrolone can change spatial ability, avoidance memory and hippocampal synaptic plasticity. Also, Nandrolone exposure produces variable effects on behavioral function such as aggression, depression and anxiety. This despite the fact that the results are contradictory. These discrepancies might be due to the differences in sex, age, dosage and treatment duration, and administration route. However, the negative results are more common than the published positive ones.

The effect of GABA-B receptors in the basolateral amygdala on passive avoidance memory impairment induced by MK-801 in rats.

MK-801 (dizocilpine) is a potent non-competitive N-methyl-[D]-aspartate (NMDA) receptor antagonist that affects cognitive function, learning, and memory. As we know, NMDA receptors are significantly involved in memory function, as well as GABA (Gamma-Aminobutyric acid) receptors. In this study, we aimed to discover the effect of GABA-B receptors in the basolateral amygdala (BLA) on MK-801-induced memory impairment. We used 160 male Wistar rats. The shuttle box was used to evaluate passive avoidance memory and locomotion apparatus was used to evaluate locomotor activity. MK-801 (0.125, 0.25, and 0.5 µg/rat), baclofen (GABA-B agonist, 0.0001, 0.001, and 0.01 µg/rat) and phaclofen (GABA-B antagonist, 0.0001, 0.001, and 0.01 µg/rat) were injected intra-BLA, after the training. The results showed that MK-801 at the dose of 0.5 µg/rat, baclofen at the doses of 0.001 and 0.01 µg/rat, and phaclofen at the doses of 0.001 and 0.01 µg/rat, impaired passive avoidance memory. Locomotor activity did not alter in all groups. Furthermore, the subthreshold dose of both baclofen (0.0001 µg/rat) and phaclofen (0.0001 µg/rat) restored the impairment effect of MK-801 (0.5 µg/rat) on memory. Also, both baclofen (0.0001 µg/rat) potentiated the impairment effect of MK-801 (0.125 µg/rat) and phaclofen (0.0001 µg/rat) potentiated the impairment effect of MK-801 (0.125 and 0.25 µg/rat) on passive avoidance memory. In conclusion, our results indicated that BLA GABA-B receptors can alter the effect of NMDA inactivation on passive avoidance memory.

The effect of ghrelin injection in the CA1 region of hippocampus on the MK801- induced memory impairment in wistar rats.

N-Methyl-D-Aspartate (NMDA) receptors are critically involved in the learning and memory formation and dizocilpine (MK-801) is an antagonist of NMDA receptor. Ghrelin plays a crucial role in learning and memory processes. The present study was conducted to the evaluation of ghrelin effect on passive avoidance memory impairment induced by MK801. In this experimental study, 24 male wistar rats were randomly distributed into 3 groups of 8 each. Passive avoidance tests of animals were evaluated using Shuttle Box apparatus. One week after the surgery, ghrelin (3 nmol) was injected intra-hippocampally, 5 min before the MK-801administration. MK-801 (0.15 mg/kg) was injected intraperitoneally (i.p.), 10 min before the test session. Pre-test injection of MK-801 significantly decreased STL (step through latency) at 24 h and 48 h (P < 0.001) and 10 days (P < 0.01) and increased TDC (time spent in dark compartment) at 24 h, 48 h and 10 days (P < 0.001) after training in comparison with control group. Pre-test injection of ghrelin + MK-801 significantly increased STL at 24 h (P < 0.01), 48 h and 10 days (P < 0.001) and decreased TDC at 24 h, 48 h and 10 days (P < 0.001) after training in comparison with MK-801 received group. It is concluded that pre-test injection of MK-801 impaired passive avoidance memory. Administration of ghrelin before MK-801 ameliorated memory impairment induced by MK-801. It is assumed that this compensative effect of ghrelin was mediated by NMDA receptor.

Ghrelin Is Effective on Passive Avoidance Memory by Altering the Expression of NMDAR and HTR1a Genes in the Hippocampus of Male Wistar Rats.

BACKGROUND: Memory-dependent psychological behaviors have an important role in life. Memory strengthening in adulthood to prevent its defects in aging is a significant issue. The ghrelin endogenous hormone improves memory by targeting glutamatergic and serotonergic circuits. Also, citicoline, a memory strengthening drug in aging, is not recommended to adults due to its side effects. The current study aims to test that ghrelin treatment, like citicoline, would improve passive avoidance memory via expression of the genes encoding the N-methyl-D-aspartate receptor (NMDAR1) and the serotonin receptor 1A (HTR1α) involved in this process. METHODS: Five groups of adult male rats received (1) saline (as control), (2) 0.5 mg/kg citicoline, or (3-5) 0.3, 1.5, and 3 nmol/µl ghrelin). The rats received the drugs via intra-hippocampal injection. Passive avoidance memory was determined using a shuttle box device. The latency to enter the dark chamber before (IL) and after (RL) injection and the total duration of the animal's presence in the light compartment (TLC) were evaluated. Then, the gene expression rates of NMDAR1 and HTR1α were measured by the Real-Time PCR. RESULTS: Ghrelin and citicoline had some similar and significant effects on passive avoidance memory, and both increased NMDAR1 and decreased HTR1α expression. CONCLUSION: Ghrelin, like citicoline, improves passive avoidance learning by altering the NMDAR1 and HTR1α expression in the hippocampus.

The effect of alpha lipoic acid on passive avoidance and social interaction memory, pain perception, and locomotor activity in REM sleep-deprived rats.

BACKGROUND: Evidence shows the vital role of sleep in the modulation of cognitive functions. Sleep deprivation (SD) can disrupt learning and memory processes. SD also affects pain perception and locomotor activity. Furthermore, alpha lipoic acid (ALA) may induce antioxidant and neuroprotective effects. ALA affects memory processes, pain subthreshold, and locomotor activity. The goal of the present study was to investigate the effect of REM (rapid-eye movement) SD and ALA on social and passive avoidance memory, locomotor activity, and pain perception. METHODS: Multiple-platform apparatus was used to induce REM SD for 24 h. Three-chamber paradigm test, the shuttle box, locomotion apparatus, and hot plate were used to assess social interaction memory, passive avoidance memory, locomotor activity, and pain perception, respectively. ALA was injected intraperitoneally at the doses of 35 and 70 mg/kg. RESULTS: 24 h REM SD impaired both types of memory. In addition, ALA (35 mg/kg) reversed REM SD-induced memory impairments. However, ALA (70 mg/kg) impaired social memory with no effect on REM SD-induced memory impairments. ALA (70 mg/kg) also decreased pain subthreshold in REM SD rats. CONCLUSION: REM SD impairs social interaction and passive avoidance memory. Furthermore, ALA may exhibit a dose-dependent manner in some cognitive tasks. ALA can induce a therapeutic effect at one dose, and an impairment effect at another dose (lower or higher), while the cognitive task and the conditions are equal.

The interaction effect of sleep deprivation and cannabinoid type 1 receptor in the CA1 hippocampal region on passive avoidance memory, depressive-like behavior and locomotor activity in rats.

Increasing evidence shows the interaction effect of cannabinoids and sleep on cognitive functions. In the present study, we aimed to investigate the interaction effect of cannabinoids type 1 receptor (CB1r) in the CA1 hippocampal region and sleep deprivation (SD) on passive avoidance memory and depressive-like behavior in male Wistar rats. We used water box apparatus to induce total SD (TSD) for 24 h. The shuttle-box was applied to assess passive avoidance memory and locomotion apparatus was applied to assess locomotor activity. Forced swim test (FST) was used to evaluate rat's behavior. ACPA (CB1r agonist) at the doses of 0.01, 0.001 and 0.0001 µg/rat, and AM251 (CB1r antagonist) at the doses of 100, 10 and 1 ng/rat were injected intra-CA1, five minutes after training via stereotaxic surgery. Results showed SD impaired memory. ACPA at the doses of 0.01 and 0.001 µg/rat impaired memory and at all doses did not alter the effect of SD on memory. AM251 by itself did not alter memory, while at lowest dose (1 ng/rat) restored SD-induced memory deficit. Both drugs induced depressive-like behavior in a dose-dependent manner. Furthermore, both drugs decreased swimming at some doses (ACPA at 0.0001 µg/rat, AM251 at 0.001 and 0.01 ng/rat). Also, ACPA at the highest dose increased climbing of SD rats. In conclusion, we suggest CB1r may interact with the effect of SD on memory. Additionally, cannabinoids may show a dose-dependent manner in modulating mood and behavior. Interestingly, CB1r agonists and antagonists may exhibit a similar effect in some behavioral assessments.