Effect of lead exposure on memory processes in mice after cerebral oligemia

The purpose of this study was to find out whether the effect of acute exposure to lead on memory processes in mice could be exacerbated by cerebral oligemia. Adult mice were subjected to 30 min of bilateral clamping of carotid arteries (BCCA) and then treated intraperitoneally with lead acetate at a single dose of: 29.3 mg/kg, 58.6 mg/kg or 87.9 mg/kg. Long-term memory was assessed in the passive avoidance task while spontaneous alternation was evaluated using the Y-maze task. Performance of the tasks was tested on the 2nd, 7th and 14th post-surgical day. On the 14th post-surgical day, significant retention deficits in passive avoidance performance were only observed in BCCA mice injected with the 87.9 mg/kg lead. Co-exposure to cerebral oligemia and lead did not change spontaneous alternation in the Y-maze task. These results show that cerebral oligemic hypoxia combined with acute lead exposure may cause selective and long-lasting impairment in memory function.     

Effects of selective inhibition of N-acetylated-alpha-linked-acidic dipeptidase (NAALADase) on mice in learning and memory tasks

The purpose of the present study was to examine the effects of 2-(phosphonomethyl)-pentanedioic acid (2-PMPA), a selective inhibitor of N-acetylated-alpha-linked-acidic dipeptidase (NAALADase, glutamate carboxypeptidase II), an enzyme catalyzing the cleavage of glutamate from the neuropeptide N-acetyl-aspartyl-glutamate (NAAG), on memory processes in mice. Long-term memory was evaluated in step-through passive avoidance task while alternation behavior, as a measure involving spatial working memory, was assessed in Y-maze task. Additionally, horizontal activity was evaluated by means of electronically monitored locomotor activity system. The mice were treated with either 2-PMPA (50, 100 and 150 mg/kg i.p.) or N-methyl-d-aspartate (NMDA) receptor antagonist, (5R,10S)-(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclo-hepten-5,10-imine hydrogen maleate (MK-801) at doses of: 0.05, 0.1, 0.15 and 0.2 mg/kg i.p., as a comparator. In the passive avoidance task, the drugs were administered once before or immediately after training, and before retention test. 2-PMPA at the doses used did not affect retention of passive avoidance; however, it increased the latency to enter the dark box during the training day. In the Y-maze task, 2-PMPA (150 mg/kg i.p.) impaired spontaneous alternation and reduced locomotion while the lower dose of 100 mg/kg was ineffective. In the locomotor activity test, 2-PMPA (100 and 150 mg/kg i.p.) did not significantly affect horizontal activity. MK-801 (0.2 mg/kg i.p.) injected before training reduced retention in the passive avoidance task. In the Y-maze task, MK-801 (0.1 mg/kg i.p.) impaired alternation behavior and considerably increased locomotion in the Y-maze and locomotor activity test. These results indicate that NAALADase inhibition may impair alternation behavior.     

Cerebral oligemic hypoxia and MK-801 treatment: effect on alternation behavior in mice

It is known that glutamatergic system is one of neurotransmitter systems affected by a transiently reduced oxygen supply. The aim of the present study was to examine the effects of MK-801, a noncompetitive NMDA receptor antagonist, on spontaneous alternation in mice exposed to cerebral oligemic hypoxia. Spontaneous alternation behavior and locomotor activity were evaluated using the Y-maze task. Transient cerebral oligemia was induced by bilateral clamping of carotid arteries (BCCA) for 30 min under pentobarbital anesthesia. MK-801 was injected 48 h after BCCA or sham surgery, 30 min before the test session. Treatment with MK-801 (0.1 mg/kg ip) impaired spontaneous alternation both in sham-operated and BCCA mice. MK-801 (0.1 mg/kg ip) significantly enhanced the locomotion of mice. The effects of MK-801 were not exacerbated by BCCA. These results show that cerebral oligemic hypoxia induced by BCCA does not change alternation behavior of mice treated with MK-801.     

Effects of systemic administration of beta-casomorphin-5 on learning and memory in mice

The effects of systemic administration of bovine beta-casomorphin-5 (Tyr-Pro-Phe-Pro-Gly), a mu-opioid receptor agonist derived from milk beta-casein, on spontaneous alternation behavior in the Y-maze (spatial short-term memory) and step-down-type passive avoidance response (non-spatial long-term memory) were investigated in mice. Intraperitoneal (i.p.) administration of beta-casomorphin-5 (0.1-20 mg/kg) did not have a significant effect on either spontaneous alternation behavior or passive avoidance response. However, a low dose (1 mg/kg, i.p.) of beta-casomorphin-5 improved scopolamine (1 mg/kg, s.c.)-induced impairment of spontaneous alternation behavior and passive avoidance response. Pretreatment with intracerebroventricular injections of beta-funaltrexamine (a mu-opioid receptor antagonist, 0.1 microg/mouse) and naloxonazine (a mu(1)-opioid antagonist, 5 microg/mouse), which did not improve scopolamine-induced impairment, prevented the ameliorating effect of beta-casomorphin-5 on scopolamine-induced impairment of passive avoidance response. These results indicated that systemic administration of a low dose (1 mg/kg, i.p.) of beta-casomorphin-5 improves the disturbance of learning and memory resulting from cholinergic dysfunction through central mediation involving mu(1)-opioid receptors.     

Competitive NMDA receptor antagonists and agonists: effects on spontaneous alternation in mice exposed to cerebral oligemia

The purpose of the present study was to investigate the effects of competitive NMDA receptor antagonists,D,L-(E)-2-amino-4-methyl-5-phosphono-3-pentenoic acid (CGP 37849) and its ethyl ester (CGP 39551), or agonist, N-methyl-D-aspartate (NMDA) on spontaneous alternation in mice exposed to cerebral oligemia. Alternation behavior was evaluated in an Y-maze. Transient cerebral oligemic hypoxia was induced by bilateral clamping of carotid arteries (BCCA) for 30 min under pentobarbital anesthesia. In BCCA mice, CGP 37849 (5 mg/kg, ip) impaired spontaneous alternation when given 48 h or 7 days after surgery. CGP 39551 (5 mg/kg, ip) had no effect.NMDA (50 mg/kg, sc) improved performance of the task in BCCA mice when tested 48 h after surgery. These results suggest that cerebral oligemic hypoxia induced by BCCA leads to functional disturbances in the central nervous system, such as spontaneous alternation impairment and increased susceptibility to NMDA receptor-related drugs. Adverse potential of cerebral oligemia may limit a therapeutic use of NMDA receptor antagonists.     

Improvement by low doses of nociceptin on scopolamine-induced impairment of learning and/or memory

The effects of fmol doses of nociceptin/orphanin FQ on scopolamine-induced impairment of learning and/or memory were examined using spontaneous alternation of Y-maze and step-down type passive avoidance tasks. While fmol doses of nociceptin alone had no effect on spontaneous alternation or passive avoidance behavior in normal mice, administration of nociceptin (10 and/or 100 fmol/mouse) 30 min before spontaneous alternation performance or the training session of the passive avoidance task, significantly improved the scopolamine-induced impairment of spontaneous alternation and passive avoidance behavior. This ameliorating effect was not antagonized by nocistatin (0.5 and 5.0 nmol/mouse, i.c.v.), naloxone benzoylhydrazone (2.3, 11.2, and 56.1 micromol/kg, s.c.) or nor-binaltorphimine (4.9 nmol/mouse, i.c.v.). These results indicated that very low doses of nociceptin ameliorate impairments of spontaneous alternation and passive avoidance induced by scopolamine, and suggested that this peptide has bidirectional modulatory effects on learning and memory; impairment at high doses and amelioration at low doses.     

Learning impairment following acute administration of the calcium channel antagonist nimodipine in mice

The effects of acute systemic administration of the Ca(2+) channel antagonist nimodipine were examined on learning capacities of adult Swiss mice. Tests included spontaneous alternation behaviour, for spatial working memory; and step-down passive avoidance and place learning in a water maze, for long-term memory. Nimodipine markedly impaired spontaneous alternation at doses of 0.3-1mg/kg i.p., and passive avoidance at doses of 0.3-3mg/kg i.p., as compared to the vehicle-treated animals. At 0.3mg/kg i.p., the drug did not alter motility in an open field, but significantly decreased performances in training trials and retention in the water maze. Subchronic nimodipine 0.3 and 1mg/kg once a day i.p. for 10 days) did not affect performances in the Y-maze and passive avoidance tests. These results show that acute nimodipine administration alters learning in adult mice, and argue for an involvement of voltage-dependent Ca(2+) channels in learning.     

Behavioral studies of the effects of moderate oligemic hypoxia caused by bilateral clamping of carotid arteries in mice. Impairment of spatial working memory

The experiments carried out on Albino Swiss mice indicated that bilateral clamping of carotid arteries (BCCA) for 30 min caused no neuronal damage but produced an increase in GABA content in the hippocampus, striatum and frontal cortex. The behavioral studies have shown that BCCA did not influence the motor coordination, the spontaneous locomotor activity, the reactivity to pain and the cataleptic response to haloperidol of the mice. However, a significant increase in amphetamine-induced hyperactivity was observed after BCCA. In mice, BCCA did not impair long-term memory and spatial working memory, reflected by alternation behavior in the Y-maze. The same dose of scopolamine impaired the working memory in mice which underwent BCCA much more than sham-operated controls. Naftidrofuryl improved the working memory in mice subjected to BCCA as measured 48 h after the surgery. Pretreatment with naftidrofuryl protected the animals against the impairment of alternation behavior caused by scopolamine administration.     

Effects of nocistatin on nociceptin-induced impairment of learning and memory in mice

We investigated the effects of nociceptin/orphanin FQ and nocistatin on learning and memory function as measured in a step-down type passive avoidance task and spontaneous alternation of Y-maze with mice. Nociceptin (0.5-5.0 nmol/mouse, i.c.v.) 30 min before the training session or Y-maze test, dose dependently shortened the step-down latency and impaired spontaneous alternation, while there was no significant effect of nocistatin (0.5-5.0 nmol/mouse). Interestingly, nocistatin (5.0 nmol) significantly improved the nociceptin (5.0 nmol)-induced impairment of learning and memory without changing motor activity or response to electric shocks. These results suggest that nocistatin, a new biologically active peptide now found to also counteract the impairment of learning and memory induced by nociceptin, plays an important role in the regulation of learning and memory process in the central nervous system.     

Effects of molsidomine on scopolamine-induced amnesia and hypermotility in the rat

Nitric oxide (NO) is hypothesized to be a novel intracellular messenger in the central nervous system. Recently, NO involvement in learning and memory processes has been proposed. Compounds that inhibit nitric oxide synthase, the key synthesizing enzyme, may block cognition, while NO donors may facilitate it. The aim of this study was to assess in the rat the effects of the NO donor molsidomine (2 and 4 mg/kg, i.p.) on memory deficits caused by scopolamine. For this purpose, the object recognition task and the step-through passive avoidance procedure were chosen. In addition, the effects of molsidomine in antagonizing the scopolamine-induced hypermotility were also examined. Scopolamine at 0.2 mg/kg (object recognition) and 0.75 mg/kg (passive avoidance) disrupted acquisition in both the tasks and induced locomotor hyperactivity at the dose of 0.2 mg/kg. Molsidomine at either dose reversed the scopolamine-induced deficits in the object recognition paradigm but did not counteract the hypermotility and the deficits occurred in the passive avoidance test. These results suggest that to some extent, the NO donor molsidomine is involved in memory processing.     

Excitatory amino acid antagonists and memory: effect of drugs acting at N-methyl-D-aspartate receptors in learning and memory tasks

The role of N-methyl-D-aspartate (NMDA) receptors in memory processes was examined using a Y-shaped maze and a step-through passive avoidance task in mice. In the Y-maze, the total number of arm entries, which represents locomotor activity and alternation behaviour, thought to reflect working memory, were measured. Competitive NMDA antagonists, CGS 19755 (cis-4-phosphonomethyl-2-piperidine-carboxylate) and CPP (3-((+)-2-carboxypiperazin-4-yl)-propyl-1-phosphate), impaired spontaneous alternation at doses which reduced locomotion of mice. N-Methyl-D-aspartate prevented the impairment of alternation and decrease of locomotor activity produced by CGS 19755 and CPP. These results suggest that NMDA-dependent processes are involved in the mechanisms of working memory. In contrast, the non-competitive NMDA antagonist, MK 801 ((+)-5-methyl-10,11-dihydro-5H-dibenzo(a,d)cycloheptan-5,10-imine maleate) dramatically enhanced the total number of arm entries, while reducing alternation behaviour, N-Methyl-D-aspartate had no effect on MK 801-induced enhancement of locomotor activity and impairment of alternation. In the passive avoidance task, mice were trained to avoid entry into the dark compartment. At doses which impaired working memory in the alternation task, CPP, CGS 19755 and MK-801 reduced acquisition, when administered before training. N-Methyl-D-aspartate antagonized the effect of CPP, CGS 19755 and MK-801. Neither CPP nor MK-801 affected retention, when administered immediately after training or before testing retention. N-Methyl-D-aspartate had no effect on retention with high-intensity shock, but facilitated retention with low-intensity shock.(ABSTRACT TRUNCATED AT 250 WORDS)     

Nociceptin/orphanin FQ and nocistatin on learning and memory impairment induced by scopolamine in mice.

1. Nociceptin, also known as orphanin FQ, is an endogenous ligand for the orphan opioid receptor-like receptor 1 (ORL1) and involves in various functions in the central nervous system (CNS). On the other hand, nocistatin is recently isolated from the same precursor as nociceptin and blocks nociceptin-induced allodynia and hyperalgesia. 2. Although ORL1 receptors which display a high degree of sequence homology with classical opioid receptors are abundant in the hippocampus, little is known regarding their role in learning and memory. 3. The present study was designed to investigate whether nociceptin/orphanin FQ and nocistatin could modulate impairment of learning and memory induced by scopolamine, a muscarinic cholinergic receptor antagonist, using spontaneous alternation of Y-maze and step-down type passive avoidance tasks in mice. 4. While nocistatin (0.5-5.0 nmol mouse-1, i.c.v.) administered 30 min before spontaneous alternation performance or the training session of the passive avoidance task, had no effect on spontaneous alternation or passive avoidance behaviours, a lower per cent alternation and shorter median step-down latency in the retention test were obtained in nociceptin (1.5 and/or 5.0 nmol mouse-1, i.c.v.)-treated normal mice. 5. Administration of nocistatin (1.5 and/or 5.0 nmol mouse-1, i.c.v.) 30 min before spontaneous alternation performance or the training session of the passive avoidance task, attenuated the scopolamine-induced impairment of spontaneous alternation and passive avoidance behaviours. 6. These results indicated that nocistatin, a new biologically active peptide, ameliorates impairments of spontaneous alternation and passive avoidance induced by scopolamine, and suggested that these peptides play opposite roles in learning and memory.     

Pharmacological study of TA-0910, a new thyrotropin-releasing hormone (TRH) analog (IV): Effects on experimental memory impairment in mice and rats

The effects of a new TRH analog, TA-0910, orally administered, on experimental memory impairments for the one-trial passive avoidance response in anoxic mice (light-dark box), active avoidance response in basal forebrain (BF)-lesioned rats (shuttle box), and delayed alternation task in scopolamine-treated rats (T-maze) were studied. In mice, TA-0910 (3-30 mg) administered 60 min before the retention trial dose-dependently prolonged the passive avoidance response latency reduced by CO2-exposure that was given immediately after the acquisition trial, but not when it was given 60 min before the acquisition or just after the anoxic treatment. In rats, TA-0910 (0.3-3 mg/kg) administered 40-60 min before the test trial, dose-dependently prevented the reduction in mean avoidance rate caused by BF-lesioning and elevated the scopolamine (0.1 mg/kg, i.p.)-induced reduction in percent correct choice level in the alternation task. TRH (30-300 mg/kg), on the other hand, produced no improvements in any of the above tests. These results suggest that TA-0910 improves impaired memory by correcting the retrieval process of memory.     

Improvement by nefiracetam of beta-amyloid-(1-42)-induced learning and memory impairments in rats

1. We have previously demonstrated that continuous i.c.v. infusion of amyloid beta-peptide (A beta), the major constituent of senile plaques in the brains of patients with Alzheimer's disease, results in learning and memory deficits in rats. 2. In the present study, we investigated the effects of nefiracetam [N-(2,6-dimethylphenyl)-2-(2-oxo-1-pyrrolidinyl) acetamide, DM-9384] on A beta-(1-42)-induced learning and memory deficits in rats. 3. In the A beta-(1-42)-infused rats, spontaneous alternation behaviour in a Y-maze task, spatial reference and working memory in a water maze task, and retention of passive avoidance learning were significantly impaired as compared with A beta-(40-1)-infused control rats. 4. Nefiracetam, at a dose range of 1-10 mg kg(-1), improved learning and memory deficits in the A beta-(1-42)-infused rats when it was administered p.o. 1 h before the behavioural tests. 5. Nefiracetam at a dose of 3 mg kg(-1) p.o. increased the activity of choline acetyltransferase in the hippocampus of A beta-(1-42)-infused rats. 6. Nefiracetam increased dopamine turnover in the cerebral cortex and striatum of A beta-(1-42)-infused rats, but failed to affect the noradrenaline, serotonin and 5-hydroxyindoleacetic acid content. 7. These results suggest that nefiracetam may be useful for the treatment of patients with Alzheimer's disease.     

Protective Effect of Arabinoxylan against Scopolamine-Induced Learning and Memory Impairment

The purpose of this study is to investigate the memory enhancing effect and underlying molecular mechanism of arabinoxylan (AX), a major component of dietary fiber in wheat against scopolamine (SCO)-induced amnesia in Sprague-Dawley (SD) rats. Diverse behavior tests including Y-maze, Morris water maze, and passive avoidance tests were performed to measure cognitive functions. SCO significantly decreased the spontaneous alterations in Y-maze test and step-through latency in passive avoidance test, whereas increased time spent to find the hidden platform in Morris water maze test compared with the sham control group. In contrast, oral administration of AX (25 mg/kg and 50 mg/kg) effectively reversed the SCO-induced cognitive impairments in SD rats. Furthermore, AX treatment up-regulated the expression of brain-derived neurotrophic factor (BDNF) in the cortex and hippo-campus via promoting activation of cAMP response element binding protein (CREB). Therefore, our findings suggest that AX can improve SCO-induced learning and memory impairment possibly through activation of CREB and up-regulation of BDNF levels, thereby exhibiting a cognition-enhancing potential.     

Chronic treatment with caffeine blunts the hyperlocomotor but not cognitive effects of the<Emphasis Type="Italic"> N</Emphasis>-methyl-<Emphasis Type="SmallCaps">d</Emphasis>-aspartate receptor antagonist MK-801 in mice

Rationale. Administration of N-methyl-d-aspartate (NMDA) receptor antagonists produce hyperlocomotion and cognitive deficits in rodents. Activation of NMDA receptors promotes adenosine release, and adenosine agonists prevent central effects of NMDA receptor antagonists. We hypothesized that if NMDA receptor antagonists require adenosine to produce behavioral effects, mice tolerant to the adenosine receptor antagonist caffeine would have a diminished response to NMDA receptor antagonists. Objectives. To evaluate MK-801-induced hyperlocomotion and cognitive deficits after chronic caffeine treatment in mice. Methods. Locomotor activity was analyzed in a computerized system, spontaneous alternation was assessed in the Y-maze and long-term memory was assessed with the inhibitory avoidance task in mice. Results. Mice chronically treated with caffeine in drinking solution (1 mg/ml for 7 days) presented normal habituation and substantial tolerance to acute caffeine (30 mg/kg, i.p.) locomotor effects. MK-801 (0.25 mg/kg, i.p.) produced pronounced hyperlocomotion in water-treated mice, but this effect was abolished in caffeine-drinking mice. Chronic caffeine treatment had no influence on either normal or MK-801-induced deficits in spontaneous alternation and inhibitory avoidance tasks. Conclusion. Hyperlocomotion induced by MK-801 may be mediated by reduced adenosinergic activity. These results also suggest that locomotor and cognitive effects of MK-801 can be dissociated and are distinctly modulated. Finally, these findings agree with the adenosine hypofunction model of schizophrenia, since NMDA receptor antagonists are a pharmacological model for this disorder. Electronic Publication     

Effect of the flavonoid, oroxylin A, on transient cerebral hypoperfusion-induced memory impairment in mice

Oroxylin A is a flavonoid compound that is found in the root of Scutellaria baicalensis Georgi. The aim of this study was to determine the effects of oroxylin A on memory impairment induced by transient bilateral common carotid artery occlusion (2VO) in mice. The ameliorating effect of oroxylin A on memory impairment was investigated using a passive avoidance task, the Y-maze task, and the Morris water maze task in mice. Oroxylin A was found to significantly reverse 2VO-induced cognitive impairments in the passive avoidance and Y-maze tasks in a dose dependant manner (P<0.05). Moreover, oroxylin A (5 mg/kg, p.o.) shortened the escape-latency and prolonged swimming times in the target quadrant during the probe trial in the Morris water maze task (P<0.05). Histochemical and immunohistochemical studies showed that the number of Nissl bodies and OX-42 positive cells in the hippocampal CA1 and dentate gyrus regions were attenuated by oroxylin A. Moreover, phosphorylated cAMP response element-binding protein (CREB) and brain derived neurotrophic factor (BDNF) positive cell numbers were markedly increased in animals treated with oroxylin A than in untreated 2VO controls. These results suggest that oroxylin A dramatically attenuates the memory impairment induced by 2VO, and that this effect may be mediated by the neuroprotective effects of oroxylin A as supported oroxylin A induced reductions in activated microglia and increases in BDNF expression and CREB phosphorylation.     

Attenuation by a sigma1 (sigma1) receptor agonist of the learning and memory deficits induced by a prenatal restraint stress in juvenile rats

1. Stress during pregnancy results in complex neurochemical and behavioral alterations throughout the offspring lifetime. We here examined the impact of prenatal stress (PS) on memory functions in male and female offspring and report the efficacy of a selective sigma(1) (sigma(1)) receptor agonist, igmesine, in alleviating the observed deficits. 2. Dams received an unpredictable 90-min duration restraint stress from gestational day E17 to E20. Learning was examined in offspring between day P24 and P36 using spontaneous alternation in the Y-maze, delayed alternation in the T-maze, water-maze learning and passive avoidance. 3. Both male and female PS rats showed impairments of spontaneous and delayed alternation performances. Acquisition of a fixed platform position in the water-maze was unchanged in PS rats, but the probe test revealed a diminution of time spent in the training quadrant. Acquisition of a daily changing platform position demonstrated impaired working memory for male and female PS rats. Finally, passive avoidance deficits were observed. 4. Pretreatment with the selective sigma(1) agonist igmesine (1-10 mg x kg(-1) i.p.) reversed the PS-induced learning deficits in offspring rats for each test. The sigma(1) antagonist BD1063 failed to affect performances alone but blocked the igmesine effect, confirming the involvement of the sigma(1) receptor. 5. PS thus induces delayed memory deficits, affecting spatial and nonspatial, short- and long-term memories in juvenile male and female offspring rats. Activation of the sigma(1) neuromodulatory receptor allows a significant recovery of the memory functions in PS rats.     

Effect of a new anxiolytic, DN-2327, on learning and memory in rats.

The effects of a new anxiolytic, (2-(7-chloro-1,8-naphthyridin-2-yl)-3- [(1,4-dioxa-8-azaspiro[4.5]dec-8-yl)-carbonylmethyl] isoindolin-1-one (DN-2327), on the execution of step-through passive avoidance and delayed spontaneous alternation tasks were assessed and compared with those of diazepam (DZP) and buspirone. DN-2327 and buspirone (both 10 and 20 mg/kg, PO) impaired performance in the 48-h passive avoidance recall test when given prior to the test session, but not when given before the training trial. DZP impaired the performance at doses of more than 5 and more than 10 mg/kg PO when given prior to the test session and when given before the training trial, respectively. The action of DZP (10 mg/kg PO) when given before the training trial was antagonized by flumazenil (20 mg/kg, IP) and tended to be antagonized by DN-2327 (10 and 30 mg/kg, PO), but was not affected by buspirone. No evidence for possible amnesic effects of DN-2327 or buspirone on working memory was found in the delayed spontaneous alternation task, but DZP (3 and 10 mg/kg, PO) caused significant impairment of working memory. Electroshock sensitivities detected by flinch, jump, and vocalization thresholds were not influenced significantly by DN-2327 (30 and 100 mg/kg, PO), DZP (10 and 30 mg/kg, PO) or buspirone (30 and 100 mg/kg, PO).(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of nicotine on memory impairment induced by blockade of muscarinic,nicotinic and dopamine D2 receptors in rats

Scopolamine dose-dependently inhibits passive avoidance latency and decreases spontaneous alternation in the Y-maze, suggesting effects on long-term and short-term memory, respectively. Chlorisondamine (10 mg/kg), a compound which produces a long-lasting central nicotinic receptor blockade, did not affect short-term and long-term memory performance. In normal rats, nicotine at the doses of 0.3, 1.0, and 3.0 mg/kg administered once had a facilitating effect on short-term memory; a higher dose (3.0 mg/kg) did not show a more pronounced effect than a lower one (0.3 mg/kg). Nicotine, by activating the nicotinic acetylcholine receptors, attenuated the impairment of short-term memory induced by muscarinic or dopamine D2 receptor blockade. On long-term memory, a single dose of nicotine (0.3, 1.0, 3.0 mg/kg) did not affect memory performance, but improved it after chronic (10 consecutive days, 0.3 mg/kg) administration. The antiamnesic effect of nicotine administered once was observed in scopolamine-, scopolamine+chlorisondamine- or sulpiride-treated rats. These results suggest that the antiamnesic effect of nicotine can result from an action at nicotinic receptors subtypes not blocked by chlorisondamine or at nonnicotinic receptors.