Reference Memory In Rats Research Articles

Concurrent exposure to light and traffic noise pollution augments behavioral deficits in rats: Protective effect of curcumin

The current study was aimed to explore the effect of light and traffic noise pollution exposure on behavioral and neurochemical deficits in adult male Wistar rats. We hypothesized that exposure to these pollutants alone or in combination may cause behavioral deficits in rats. Animals were allocated into different groups and were exposed to either varying light cycles (150 lx-5 lx, 14:10 h) or traffic noise with sound level 100 dBA for 6 h/day or both for 28 days. Concurrently, Curcumin (100 mg/kg; per oral; 28 days) was administered in varying light cycles and noise exposed animal groups to study the preventive effect. After the exposure time, the Morris water maze test, elevated plus maze test, novel object recognition test, locomotor activity test, and forced swimming test were conducted. The neurobehavioral results suggested that only combined exposure of light and noise pollution markedly impaired the learning as well as spatial and reference memory in rats. Furthermore, we found significant anxiety (less no. of open arm entries in EPM) and depressive-like behavior (increased immobility time) in light or/and traffic noise pollution exposed group animals in comparison to normal control groups. Curcumin treatment significantly prevented the behavioral anomalies in combined light and noise exposed rats. Furthermore, our results revealed augmentation of acetylcholinesterase, oxidative stress markers and interleukin (IL)-1β in the hippocampal region of noise and light-exposed groups which were markedly ameliorated by curcumin. In conclusion, our results suggest that curcumin significantly modulates light and noise pollution exposed behavioral and neurochemical anomalies in rats.

Minocycline Protects Against Lipopolysaccharide-Induced Cognitive Impairment and Oxidative Stress: Possible Role of the CREB-BDNF Signaling Pathway.

The oxidative stress-induced dysregulation of the cyclic AMP response element-binding protein- brain-derived neurotrophic factor (CREB-BDNF) cascade has been linked to cognitive impairment in several studies. This study aimed to investigate the effect of minocycline on the levels of oxidative stress markers, CREB, and BDNF in lipopolysaccharide (LPS)-induced cognitive impairment. Fifty adult male Sprague Dawley rats were divided randomly into five groups. Group 1 was an untreated control group. Groups 2, 3, 4 and 5 were treated concurrently with LPS (5mg/kg, i.p) once on day 5 and normal saline (0.7ml/rat, i.p) or minocycline (25 and 50mg/kg, i.p) or memantine (10mg/kg, i.p) once daily from day 1 until day 14, respectively. From day 15 to day 22 of the experiment, Morris Water Maze (MWM) was used to evaluate learning and reference memory in rats. The levels of protein carbonyl (PCO), malondialdehyde (MDA), catalase (CAT), and superoxide dismutase (SOD) were determined by enzyme-linked immunosorbent assay (ELISA). CREB and BDNF expression and density were measured by immunohistochemistry and western blot analysis, respectively. LPS administration significantly increased escape latency to the hidden platform with decreased travelled distance, swimming speed, target crossings and time spent in the target quadrant. Besides, the hippocampal tissue of LPS rats showed increased levels of PCO and MDA, decreased levels of CAT and SOD, and reduced expression and density of BDNF and CREB. Treatment with minocycline reversed these effects in a dose-dependent manner, comparable to the effects of memantine. Both doses of minocycline treatment protect against LPS-induced cognitive impairment by reducing oxidative stress and upregulating the CREB-BDNF signalling pathway in the rat hippocampus.

The modulation of the spatial reference memory by the orexinergic system of the dorsal raphe nucleus

The dorsal raphe nucleus (DRN) is a brainstem nucleus involved in the pathophysiology of the depression, through its serotoninergic innervation. Furthermore, depressive symptoms in patients are also associated with some memory and sleep complaints. Anatomical evidence confirmed the presence of projections from the lateral hypothalamus to serotonergic neurons of the dorsal raphe nucleus (DRN). These projection fibers release orexin neuropeptides which play roles in the spatial memory. Both of the orexinergic receptors are widely distributed in dorsal raphe nucleus. Therefore, the present work was aimed to assess the probable roles of orexin 1 and 2 receptors using an orexin 1 receptor antagonist, SB-334867-A, and an orexin 2 receptor antagonist, TCS-OX2–29 in the DRN on the retrieval, and consolidation phases of spatial reference memory in the Morris water maze (MWM) task. The results demonstrated that blocking orexin 1 receptors in the DRN impairs the process of memory consolidation in the spatial MWM via increasing in the time of the escape latency of the probe day. Blocking these receptors did not affect the retrieval phase of MWM learning. Furthermore, blocking of the orexin 2 receptors in this area did not affect neither consolidation nor retrieval phases of the memory. In conclusion, orexin 1 receptors in the DRN play major roles in the consolidation of the spatial reference memory in rats.

The Imidazoline Receptor Antagonists Idazoxan and Efaroxan Improve the Spatial and Reference Memory in Rats

Experimental studies and clinical trials revealed the complex interconnections between imidazoline system and various other mediators such as epinephrine, norepinephrine; thus, explain their involvement in the pathophysiological mechanisms of different motor, behavioral and cognitive disturbances. In this study, we tested the influence induced by idazoxan and efaroxan on the cognitive performances in rats. Groups of 6 adult male Wistar rats were treated intraperitoneally according to the following protocol: group I (Control): distilled water 0.3 ml/100g; group II (IDZ): 3 mg/kg idazoxan and group III (EFR): 1 mg/kg efaroxan. The effects of the imidazoline receptor antagonists on the rats cognitive functions were assessed using the radial-arm maze, in order to count the time spent into the arms, the number of baited arms visited, but previously explored (working memory errors); the time taken to consume all baits and the number of entering in non-baited arms (reference memory errors). The data were expressed as mean +/- standard deviation, and statistically analyzed using SPSS version 17.0 Software for Windows, followed by ANOVA one-way method. The administration of IDZ, as well as of EFR was accompanied by a substantial diminution in the number of working memory errors, and the period of time to consume all baits, statistically significant (p[0.01) compared to control group. The use of these two imidazoline receptors antagonists resulted in a considerable decrease in the reference memory errors number, statistically significant (p[0.01) compared to the group treated with distilled water. The influence of IDZ on the evaluated parameters was more accentuated than the effects induced by EFR in all sessions of testing, in this behavioral experimental model. Our findings indicate that treatment with both imidazoline receptor antagonists, idazoxan and efaroxan was associated by a facilitation of the short-term memory retention, an enhancement of discriminative spatial learning, and an improvement of long-term memory performance in radial arm maze in rats.

Anterior thalamic nuclei lesions have a greater impact than mammillothalamic tract lesions on the extended hippocampal system.

The anterior thalamic nuclei (ATN), mammillary bodies and their interconnecting fiber tract, the mammillothalamic tract (MTT), are important components of an extended hippocampal circuit for episodic memory. In humans, damage to the MTT or ATN in many disorders is associated with severe anterograde amnesia and it is assumed that their influence on memory is functionally equivalent. The relative influence of these two structures on memory has not, however, been assessed explicitly. Here, a direct comparison found that only ATN lesions impaired spatial reference memory in rats. ATN lesions produced more severe deficits on spatial working memory and reduced zif268 expression to a greater degree and in more corticolimbic sites than did MTT lesions. Conversely, MTT lesions reduced NeuN cell counts in all three subregions of the MB to a greater extent than did ATN lesions, so their relative impact cannot be explained by retrograde neuropathology of the MB. Hence ATN injury causes a more critical dysfunction than would be expected by an emphasis on the indirect influence of brainstem inputs to the extended memory system. The greater ATN lesion deficits found here may represent the consequence of disruption to the direct connections of the ATN with both hippocampal and cortical sites.

Effects of concomitant methylphenidate and ethanol administration on working and reference memory in rats

Recent studies have suggested that college students are heavily engaged in non-medical use of stimulant drugs prescribed to treat attention deficit hyperactivity disorder. This age group is also at high risk for alcohol use. Despite their potential co-abuse, little work has examined how these drugs interact to affect cognitive abilities. In fact, these drugs have opposing effects on working memory, which brings into question how they may interact to affect this particular behavior. The purpose of this research was to examine the concomitant effects of methylphenidate (MPH) and ethanol (EtOH) on working and reference memory. Rats were first trained on the radial arm maze task to establish a baseline performance rate measured as average number of reference and working memory errors. Performance was then assessed after injections of saline, MPH alone, EtOH alone, and MPH+EtOH combined. While both doses of MPH caused nonsignificant improvements in working memory, when combined with EtOH, there was an overall impairment in working and reference memory compared to other conditions. EtOH alone also decreased memory. These data indicate increased impairment of memory function with combined MPH and EtOH use. By understanding how the combination of methylphenidate and alcohol affects memory, we can better assess the risks of taking both substances simultaneously.

Adenosine A1 receptor antagonist mitigates deleterious effects of sleep deprivation on adult neurogenesis and spatial reference memory in rats

Sleep deprivation (SD) upsurges intracellular levels of adenosine, impairs adult neuronal cell proliferation (NCP) and cognition while caffeine, a non-selective adenosine A1 receptor (A1R) antagonist improves cognition and adult NCP during SD. We examined the selective antagonistic effects of adenosine A1R using 8-cyclopentyl-1,3-dimethylxanthine (8-CPT) on impairment of spatial reference memory and adult NCP during 48h SD. Adult male Sprague Dawley rats were sleep deprived for 48h, using an automatic cage vibrating stimulus based on animal activity. Spatial reference memory was tested as a measure of cognitive performance employing Morris Water Maze. Rats were given 8-CPT dissolved in 50% dimethyl sulfoxide (DMSO), twice daily (10mg/kg, i.p.) along with 5-bromo-2-deoxyuridine (BrdU) (50mg/kg/day, i.p.). The rats treated with 8-CPT showed significantly short mean latency and path-length to reach the platform compared to the SD rats. Consistent with these findings, 8-CPT-treated group was found to have significantly increased the number of BrdU, Ki-67 and doublecortin (DCX) positive cells. However, no significant difference was seen in NeuN expression in the Dentate Gyrus (DG). Brain-derived neurotropic factor (BDNF) expression in the DG and CA1 region was observed to decrease significantly after SD and be rescued by 8-CPT treatment. Furthermore, latency to reach platform showed a negative correlation with number of BrdU, DCX type-1 cells and BDNF expression in DG. Thus, it may be concluded that treatment with 8-CPT, an adenosine A1R antagonist during SD mitigates SD induced decline in spatial reference memory and adult NCP possibly via up regulation of BDNF levels in DG and CA1 regions.

Curcumin Improves Amyloid β-Peptide (1-42) Induced Spatial Memory Deficits through BDNF-ERK Signaling Pathway.

Curcumin, the most active component of turmeric, has various beneficial properties, such as antioxidant, anti-inflammatory, and antitumor effects. Previous studies have suggested that curcumin reduces the levels of amyloid and oxidized proteins and prevents memory deficits and thus is beneficial to patients with Alzheimer’s disease (AD). However, the molecular mechanisms underlying curcumin’s effect on cognitive functions are not well-understood. In the present study, we examined the working memory and spatial reference memory in rats that received a ventricular injection of amyloid-β1-42 (Aβ1-42), representing a rodent model of Alzheimer’s disease (AD). The rats treated with Aβ1-42 exhibited obvious cognitive deficits in behavioral tasks. Chronic (seven consecutive days, once per day) but not acute (once a day) curcumin treatments (50, 100, and 200 mg/kg) improved the cognitive functions in a dose-dependent manner. In addition, the beneficial effect of curcumin is accompanied by increased BDNF levels and elevated levels of phosphorylated ERK in the hippocampus. Furthermore, the cognition enhancement effect of curcumin could be mimicked by the overexpression of BDNF in the hippocampus and blocked by either bilateral hippocampal injections with lentiviruses that express BDNF shRNA or a microinjection of ERK inhibitor. These findings suggest that chronic curcumin ameliorates AD-related cognitive deficits and that upregulated BDNF-ERK signaling in the hippocampus may underlie the cognitive improvement produced by curcumin.

Effects of Novel Monoamine Oxidases and Cholinesterases Targeting Compounds on Brain Neurotransmitters and Behavior in Rat Model of Vascular Dementia

Neurodegenerative disorders are associated with different neurochemical and morphological alterations in the brain leading to cognitive and behavioural impairments. New therapeutic strategies comprise multifunctional drugs. The aim of the presented studies is to evaluate in vivo the novel compounds - ASS188 and ASS234 - which combine the benzylpiperidine moiety of the acetylcholinesteras (AChE) inhibitor donepezil and the indolyl propargylamino moiety of the monoaminooxidase (MAO) inhibitor, N-[(5-benzyloxy-1- methyl-1H-indol-2-yl)methyl]-N-methylprop-2-yn-1-amine, with respect to their influence on cerebral amine neurotransmitters systems and neuroprotective activity. The presumed therapeutic potential of these compounds has been evaluated following their administration to rats with experimental vascular dementia. A rat model of the permanent bilateral occlusion of the common carotid arteries (BCCAO) and the holeboard memory test were employed for this purpose. Wistar rats were used, either intact or 1 day after BCCAO. ASS188 (1 mg/kg) and ASS234 (5 mg/kg) were given s.c. for 5 consecutive days. Working and reference memory in rats was evaluated by holeboard tests before- and 7 and 12 days after BCCAO. The activities of MAOs, AChE and histamine N-methyltransferase (HMT), as well as cerebral amines concentrations were assayed. A significant inhibition of brain MAO A (>95%) and weaker MAO B (ca 60%) and HMT (<30%) and reduced AChE activities were recorded with a pronounced (2 - 10 fold) increase in the cerebral concentrations of serotonin, dopamine, and noradrenaline and smaller rises (up to 30%) of histamine. The BCCAO rats treated with ASS188 or ASS234 tended to perform holeboard tests better than the BCCAO untreated group, indicating a beneficial effect of the administered therapeutics.

獲得後のNMDA受容体阻害は空間記憶保持を向上させる

We investigated the effect of a post-training chronic infusion of N-methyl-D-aspartate (NMDA) receptor blocker on retention of spatial reference memory in rats. In Experiment 1, we trained 4 groups of rats for 4 days (4 trials/ day) in the Morris water maze task. In a single probe trial after retention intervals of 1, 7, 14, and 28 days, the 1-day group showed more goal crossings than shown by the other 3 groups. In Experiment 2, a chronic infusion of the NMDA receptor antagonist D-2-amino-5-phosphonovaleric acid (D-AP5) or a control vehicle into the lateral ventricle was initiated 1 day after the training session, and continued for 6 days. In the subsequent probe trial (7 days after training), the rats that had received the D-AP5 infusion showed significantly more goal crossings than the controls. These findings suggest that an NMDA receptor blockade following acquisition facilitates retention of spatial reference memory.

The Effect of Cigarette Smoke Maintained at 10-32 ppm of Carbon Monoxide on Reference Memory and Count of Pyramidal Cells of the Hippocampus of Wistar Rats.

AIM: Numerous works relating to memory had obtained several different results, some contrasting others. Hence, the need for the current work aimed at revealing the structural and functional implication of exposure to cigarette smoke at low concentration (10-32 part per million) on the memory system, the hippocampus in particular. METHOD: The methodology involved the use of reference time records obtained from Morris water maze task before and after the exposure to cigarette smoke. These reference time records served as indicators of the functional integrity of the hippocampus. Additionally, the pyramidal cell layer of CA1 and CA2 of the hippocampus of the male rats was photomicrographed and uploaded onto the manual counter of the image software, then counted into either normal appearing or pyknotic appearing cells. RESULTS: The results revealed a detoriation in the post exposure reference time records of the exposed male and female rats compared to the lower post exposure time records obtained among the control male and female rats. The cell counting revealed a significant increase in the population of both the normal and pyknotic pyramidal cells in the exposed male rats. CONCLUSION: These findings imply that cigarette smoke exposure at 10-32 ppm of carbonmonoxide disrupts reference memory in rats - mostly in females - and supports both neurogenesis and cell death in the pyramidal cell layers of CA1 and CA2 regions of the hippocampus of male rats

Suppressive effect of triadimefon, a triazole fungicide, on spatial learning and reference memory in rats

Although some central effects of triadimefon, a triazole fungicide, have been reported, its effects on spatial memory have not been examined. In this study, we used the Morris water maze to study the effect of triadimefon on spatial learning and memory in rats. To elucidate the mechanism of this effect, we also measured the retinoic acid concentration in the hippocampus by high-performance liquid chromatography. Our data showed that triadimefon inhibited spatial learning and impaired spatial reference memory, and decreased hippocampal retinoic acid concentration. There is evidence that triadimefon can regulate the metabolism of retinoic acid, which serves a critical function in the development and maintenance of spatial memory. Therefore, we speculate that the reduction in hippocampal retinoic acid concentration induced by triadimefon might be responsible for its suppressive effect on spatial learning and reference memory.

Selective and nonselective neuronal NOS inhibitors impair cognitive function in the three panel runway and passive avoidance tasks in rats

The aim of this study was to compare the effects of both neuronal NOS (nNOS) and inducible NOS (iNOS) inhibitor 2-iminobiotin, with the more selective nNOS inhibitor Nω-propyl-L-arginine (NPLA) and selective inducible NOS (iNOS) inhibitor aminoguanidine, on emotional learning, working memory and reference memory, by using three panel runway and passive avoidance paradigm in order to clarify the role of distinct isoforms of NOS in the regulation of learning and memory functions. NPLA and 2-iminobiotin significantly increased the number of errors and latency of working and reference memory performances of rats in three panel runway paradigm and impairs retention for the passive avoidance task. However, aminoguanidine did not affect cognitive functions in three panel runway and passive avoidance test. The effect of NPLA and 2-iminobiotin was reversed by pretreatment with a NOS substrate L-arginine. In conclusion, NPLA and 2-iminobiotin impaired cognitive functions in different kind of tasks used in this study and the effect of NPLA and 2-iminobiotin was found to be NO-dependent. Our results may confirm that nNOS plays the key role on emotional learning, working memory and reference memory in rats.

Xamoterol impairs hippocampus-dependent emotional memory retrieval via Gi/o-coupled β2-adrenergic signaling

Xamoterol, a partial β(1)-adrenergic receptor agonist, has been reported to impair the retrieval of hippocampus-dependent spatial reference memory in rats. In contrast, xamoterol restores memory retrieval in gene-targeted mice lacking norepinephrine (NE) and in a transgenic mouse model of Down syndrome in which NE levels are reduced. Restoration of retrieval by xamoterol in these two models complements the observation that NE and β(1) signaling are required for hippocampus-dependent retrieval of contextual and spatial reference memory in wild-type mice and rats. Additional evidence indicates that cAMP-mediated PKA and Epac signaling are required for the retrieval of hippocampus-dependent memory. As a result, we hypothesized that xamoterol has effects in addition to the stimulation of β(1) receptors that, at higher doses, act to counter the effects of β(1) signaling. Here we report that xamoterol-induced disruption of memory retrieval depends on β(2)-adrenergic receptor signaling. Interestingly, the impairment of memory retrieval by xamoterol is blocked by pretreatment with pertussis toxin, an uncoupling agent for G(i/o) signaling, suggesting that β(2) signaling opposes β(1) signaling during memory retrieval at the level of G protein and cAMP signaling. Finally, similar to the time-dependent roles for NE, β(1), and cAMP signaling in hippocampus-dependent memory retrieval, xamoterol only impairs retrieval for several days after training, indicating that its effects are also limited by the age of the memory. We conclude that the disruption of memory retrieval by xamoterol is mediated by G(i/o)-coupled β(2) signaling, which opposes the G(s)-coupled β(1) signaling that is transiently required for hippocampus-dependent emotional memory retrieval.

Immediate Splenectomy Decreases Mortality and Improves Cognitive Function of Rats After Severe Traumatic Brain Injury

Traumatic brain injury (TBI) is a major health problem all over the world. It frequently causes a considerable social burden because of its high incidence of death and long-term disability, especially in the case of severe TBI. Recent studies revealed that the spleen might contribute to secondary brain injury after ischemia or intracerebral hemorrhage. The purpose of this study was to evaluate the significance of the spleen in traumatic brain edema after severe TBI. We established a severe TBI model with rats and performed splenectomy to observe the mortality, brain water content, cognitive function (water maze), and cytokines levels, including interleukin (IL)-1β, tumor necrosis factor-α (TNF-α), IL-6, and IL-10, in the blood plasma (enzyme-linked immunosorbent assay) and their mRNA expression levels in injured brain tissue (quantitative reverse transcriptase-polymerase chain reaction). The immediate splenectomy after TBI significantly decreased the death rate from 35.42% to 14.89% and eliminated the brain water content of the injured brain, especially at days 2 and 3. The Morris water maze assessment showed an improved spatial reference memory in rats that underwent both TBI and splenectomy when compared with those in the TBI group, 4 weeks later. Splenectomy reduced the IL-1β, TNF-α, and IL-6 contents in the blood serum after TBI, and the mRNA expression levels of IL-1β, TNF-α, and IL-6 in the ipsilateral brain tissue also decreased. Our study demonstrates that splenectomy has a protective effect on rats with severe TBI by inhibiting proinflammatory cytokines, including IL-1β, TNF-α, and IL-6, both systematically and locally in the injured brain, hence leading to a decreased mortality and improved cognitive function.

Enhancement of reference memory in aged rats by specific activation of 5-HT4 receptors using an olfactory associative discrimination task

In normal aging, or pathological brain diseases in humans, implicit memory (or procedural memory in rats) is spared while explicit memory (or reference memory in rats) is deeply impaired. Selective activation of 5-HT4 receptors by a partial 5-HT4 receptor agonist (SL65.0155) improved memory performance in an olfactory associative discrimination task in aged rats. Detailed analysis of subcategories of long-term memory using a hippocampal-dependent olfactory associative discrimination task revealed a substantial benefit on reference memory. This agent could be used to treat early mnesic deficits observed in normal aging or in neurodegenerative disorders like Alzheimer disease.

Hormonal and monoamine signaling during reinforcement of hippocampal long-term potentiation and memory retrieval.

Recently it was shown that holeboard training can reinforce, i.e., transform early-LTP into late-LTP in the dentate gyrus during the initial formation of a long-term spatial reference memory in rats. The consolidation of LTP as well as of the reference memory was dependent on protein synthesis. We have now investigated the transmitter systems involved in this reinforcement and found that LTP-consolidation and memory retrieval were dependent on beta-adrenergic, dopaminergic, and mineralocorticoid receptor (MR) activation, whereas glucocorticoid receptors (GRs) were not involved. Blockade of the beta-adrenergic signaling pathway significantly increased the number of reference memory errors compared with MR and dopamine receptor inhibition. In addition, beta-adrenergic blockade impaired the working memory. Therefore, we suggest that beta-adrenergic receptor activation is the main signaling system required for the retrieval of spatial memory. In addition, other modulatory interactions such as dopaminergic as well as MR systems are involved. This result points to specific roles of different modulatory systems during the retrieval of specific components of spatial memory. The data provide evidence for similar integrative interactions between different signaling systems during cellular memory processes.

Histamine H 1 receptor involvement in prepulse inhibition and memory function: Relevance for the antipsychotic actions of clozapine

Histamine H 1 blockade is one of the more prominent actions of the multi-receptor acting antipsychotic clozapine. It is currently not known how much this H 1 antagonism of clozapine contributes to the therapeutic or adverse side effects of clozapine. The current studies with Sprague-Dawley rats were conducted to determine the participation of histaminergic H 1 receptor subtype in sensorimotor plasticity and memory function affected by clozapine using tests of prepulse inhibition (PPI) and radial-arm maze choice accuracy. The PPI impairment caused by the glutamate antagonist dizocilpine (MK-801) was significantly attenuated by clozapine. In the current project, we found that the selective H 1 antagonist pyrilamine also reversed the dizocilpine-induced impairment in PPI of tactile startle with an auditory prepulse. In the radial-arm maze (RAM), pyrilamine, like clozapine, impaired working memory and caused a significant dose-related slowing of response. Pyrilamine, however, decreased the number of reference memory errors. We have previously shown that nicotine effectively attenuates the clozapine-induced working memory impairment, but in the current study, nicotine did not significantly alter the effects of pyrilamine on the RAM. In summary, the therapeutic effect of clozapine in reversing PPI impairment was mimicked by the H 1 antagonist pyrilamine, while pyrilamine had a mixed effect on cognition. Pyrilamine impaired working memory but improved reference memory in rats. Thus, H 1 antagonism seems to play a role in part of the beneficial actions of antipsychotics, such as clozapine.

Effects of scopolamine and d-cycloserine on non-spatial reference memory in rats

The aim of the present work was to use a three-choice simultaneous brightness discrimination test to examine the retention of non-spatial reference memory in rats treated with scopolamine (0.5 mg/kg) alone and in combination with various concentrations of d-cycloserine (DCS) (5, 15 and 50 mg/kg). Scopolamine given 1 h before testing for retention was found to increase both the number of errors and the number of trials necessary to reach criterion. The three doses of DCS reduced this increase significantly and resulted in a U-shaped dose–response curve, where 15 mg/kg had a stronger compensatory effect than both 5 and 50 mg/kg. Control experiments were performed to confirm that the observed response was not due to non-mnemonic factors. Our results indicate that scopolamine and DCS affect non-spatial reference memory in a similar manner as shown for spatial reference memory.

Improvement of spatial memory by ( R)-α-methylhistamine, a histamine H 3-receptor agonist, on the Morris water-maze in rat

This work aims to clarify the role of histamine in learning and memory. This is done by studying the effect of administration of the histamine precursor, l-histidine (His), and the agonist of the H 3 receptor ( R)-α-methylhistamine (RAMH), on acquisition and retention of spatial reference memory in rats. Treatment with RAMH (10 mg/kg i.p.) facilitates recovery of spatial memory. In contrast, administration of His (500 mg/kg i.p.) does not affect the performance of this task. Moreover, pharmacological modulation of the cerebral histaminergic system does not impair the animal's behavioral flexibility, i.e. their ability to adapt to a new learning task in the same stimular context. Improved retention of spatial memory after a reduction in cerebral histamine confirms the modulating role of this neurotransmitter in memory processes.