Memory Deficits In Rats Research Articles

Cognitive deficits following blast injury-induced neurotrauma: possible involvement of nitric oxide.

Blast injuries, that is injuries caused by the complex pressure wave generated by some explosions, show increasing frequency throughout the world. However, whether blast injury is capable of inducing memory dysfunction has not been previously investigated. The present study examines the effects of blast injury-induced neurotrauma on memory deficit in rats. Furthermore, it is hypothesized that blast injury, stimulating nitric oxide production in the medial mesodiencephalic reticular formation and the dorsal hippocampus, both structures being involved in memory processing, may induce memory deficits. Prior to blast injury, Wistar rats were trained for an active avoidance task for 6 days. On day 6, rats that had acquired the avoidance response were subjected to whole-body blast injury, using a BT-I shock tube. Neurotrauma was confirmed by electron microscopical examination. At the completion of cognitive testing, rats were sacrificed at 3, 24 hours and 5 days after injury. The nitric oxide production in the brain structures was determined by the total nitrite/nitrate concentration, and by the expression of inducible nitric oxide synthase mRNA. The rats with blast injury revealed significant deficits in performance of the active avoidance task that persisted up to 5 days post-injury. Electron microscopical findings in both brain structures showed swellings of neurons, glial reaction, myelin debris, and increased pinocytotic activity on the fifth day following trauma. In blast injured rats, there was a significant elevation in total nitrite/nitrate levels 3 and 24 hours following injury which was comparable with the changes in the expression of inducible nitric oxide synthase mRNA. The results indicate that blast injury-induced neurotrauma is able to cause cognitive deficits.

Cognitive deficits following blast injury-induced neurotrauma: possible involvement of nitric oxide

Blast injuries, that is injuries caused by the complex pressure wave generated by some explosions, show increasing frequency throughout the world. However, whether blast injury is capable of inducing memory dysfunction has not been previously investigated. The present study examines the effects of blast injury-induced neurotrauma on memory deficit in rats. Furthermore, it is hypothesized that blast injury, stimulating nitric oxide production in the medial mesodiencephalic reticular formation and the dorsal hippocampus, both structures being involved in memory processing, may induce memory deficits. Prior to blast injury, Wistar rats were trained for an active avoidance task for 6 days. On day 6, rats that had acquired the avoidance response were subjected to whole-body blast injury, using a BT-I shock tube. Neurotrauma was confirmed by electron microscopical examination. At the completion of cognitive testing, rats were sacrificed at 3, 24 hours and 5 days after injury. The nitric oxide production in the brain structures was determined by the total nitrite/nitrate concentration, and by the expression of inducible nitric oxide synthase mRNA. The rats with blast injury revealed significant deficits in performance of the active avoidance task that persisted up to 5 days post-injury. Electron microscopical findings in both brain structures showed swellings of neurons, glial reaction, myelin debris, and increased pinocytotic activity on the fifth day following trauma. In blast injured rats, there was a significant elevation in total nitrite/nitrate levels 3 and 24 hours following injury which was comparable with the changes in the expression of inducible nitric oxide synthase mRNA. The results indicate that blast injury-induced neurotrauma is able to cause cognitive deficits.

Metabolically active rat brain slices as a model for studying neurofibrillary degeneration of Alzheimer's disease

The Renshen Shouwu capsule (RSSW) is a patented Traditional Chinese Medicine (TCM), that has been proven to improve memory and is widely used in China to apoplexy syndrome and memory deficits. To investigate the neuroprotective and therapeutic effect of the Renshen Shouwu standardized extract (RSSW) on ischemic brain neuronal injury and impairment of learning and memory related to Vascular Dementia (VD) induced by a focal and global cerebral ischemia-reperfusion injury in rats.Using in vivo rat models of both focal ischemia/reperfusion (I/R) injuries induced by a middle cerebral artery occlusion (MCAO), and VD with transient global brain I/R neuronal injuries induced by a four-vessel occlusion (4-VO) in Sprague–Dawley (SD) rats, RSSW (50,100, and 200 mg kg−1 body weights) and Egb761® (80 mg kg−1) were administered orally for 20 days (preventively 6 days+therapeutically 14 days) in 4-VO rats, and for 7 days (3 days preventively+4 days therapeutically) in MCAO rats. Learning and memory behavioral performance was assayed using a Morris water maze test including a place navigation trial and a spatial probe trial. Brain histochemical morphology and hippocampal neuron survival was quantified using microscope assay of a puffin brain/hippocampus slice with cresyl violet staining.MCAO ischemia/reperfusion caused infarct damage in rat brain tissue. 4-VO ischemia/reperfusion caused a hippocampal neuronal lesion and learning and memory deficits in rats. Administration of RSSW (50, 100, and 200 mg/kg) or EGb761 significantly reduced the size of the insulted brain hemisphere lesion and improved the neurological behavior of MCAO rats. In addition, RSSW markedly reduced an increase in the brain infarct volume from an I/R-induced MCAO and reduced the cerebral water content in a dose-dependent way. Administration of RSSW also increased the pyramidal neuronal density in the hippocampus of surviving rats after transient global brain ischemia and improved the learning and memory ability of rats with 4-VO induced vascular dementia in a dose-dependent manner.The in vivo results suggested that RSSW has significant neuroprotective effects against MCAO and 4-VO I/R injury and a therapeutic effect on cognitive disorders in VD rats. RSSW also improved the learning and memory ability of VD rats. These results convincingly demonstrated that RSSW may be useful to prevent and treat ischemia/reperfusion injury and vascular dementia disease.

The ameliorating effects of the cognitive-enhancing Chinese herbs on scopolamine-induced amnesia in rats.

Ameliorating effects were investigated of the cognitive-enhancing Chinese herbs administered orally for 1 week-Panax ginseng (PG), Panax notoginseng (PNG), Dioscorea opposita (DO), Gastrodia elata (GE), Salvia miltiorrhiza (SM), Acorus gramineus (AG), Coptis chinensis (CC), Polygonum multiflorum (PM), Cyperus rotundus (CR) and Psoralea corylifolia (PC)-on the scopolamine (SCOP)-induced amnesia by using a passive avoidance task in rats. Of ten Chinese herbs, only PG, PNG, GE and CC prolonged the SCOP-shortened STL. These results revealed that PG, PNG GE and CC administered orally for 1 week improved the SCOP-induced learning and memory deficit in rats.

Plasma Membrane Ordering Agent Pluronic F-68 (PF-68) Reduces Neurotransmitter Uptake and Release and Produces Learning and Memory Deficits in Rats

A substantial body of evidence indicates that aged-related changes in the fluidity and lipid composition of the plasma membrane contribute to cellular dysfunction in humans and other mammalian species. In the CNS, reductions in neuronal plasma membrane order (PMO) (i.e., increased plasma membrane fluidity) have been attributed to age as well as the presence of the beta-amyloid peptide-25-35, known to play an important role in the neuropathology of Alzheimer's disease (AD). These PMO increases may influence neurotransmitter synthesis, receptor binding, and second messenger systems as well as signal transduction pathways. The effects of neuronal PMO on learning and memory processes have not been adequately investigated, however. Based on the hypothesis that an increase in PMO may alter a number of aspects of synaptic transmission, we investigated several neurochemical and behavioral effects of the membrane ordering agent, PF-68. In cell culture, PF-68 (nmoles/mg SDS extractable protein) reduced [3H]norepinephrine (NE) uptake into differentiated PC-12 cells as well as reduced nicotine stimulated [3H]NE release. The compound (800-2400 microg/kg, i.p., resulting in nmoles/mg SDS extractable protein in the brain) decreased step-through latencies and increased the frequencies of crossing into the unsafe side of the chamber in inhibitory avoidance training. In the Morris water maze, PF-68 increased the latencies and swim distances required to locate a hidden platform and reduced the time spent and distance swam in the previous target quadrant during transfer (probe) trials. PF-68 did not impair performance of a well-learned working memory task, the rat delayed stimulus discrimination task (DSDT), however. Studies with 14C-labeled PF-68 indicated that significant (pmoles/mg wet tissue) levels of the compound entered the brain from peripheral (i.p.) injection. No PF-68 related changes were observed in swim speeds or in visual acuity tests in water maze experiments, rotorod performance, or in tests of general locomotor activity. Furthermore, latencies to select a lever in the DSDT were not affected. These results suggest that PF-68 induced deficits in learning and memory without confounding peripheral motor, sensory, or motivational effects at the tested doses. Furthermore, none of the doses induced a conditioned taste aversion to a novel 0.1% saccharin solution indicating a lack of nausea or gastrointestinal malaise induced by the compound. The data indicate that increases in neuronal plasma membrane order may have significant effects on neurotransmitter function as well as learning and memory processes. Furthermore, compounds such as PF-68 may also offer novel tools for studying the role of neuronal PMO in mnemonic processes and changes in PMO resulting from age-related disorders such as AD.

Long-term deprivation of oestrogens by ovariectomy potentiates beta-amyloid-induced working memory deficits in rats.

1 In the present study, we examined whether deprivation of oestrogens by ovariectomy could modify learning and memory deficits caused by a continuous intracerebroventricular (i.c.v.) infusion of amyloid beta-peptide (Abeta), the major constituent of senile plaques in AD. 2 Neither long-term (3 months) nor short-term (1 month), deprivation of oestrogens by ovariectomy caused a significant impairment in spatial learning and memory in a water maze and spontaneous alternation behaviour in a Y-maze. 3 A continuous i.c.v. infusion of Abeta-(1-42) caused spatial learning and memory deficits in both ovariectomized and sham-operated rats. 4 The Abeta-induced working memory deficits were significantly potentiated in ovariectomized rats compared with sham-operated rats when mnemonic ability was examined 3 months after ovariectomy. 5 These results suggest that long-term deprivation of oestrogens induced by ovariectomy increases susceptibility to memory deficits produced by Abeta-(1-42) in rats.

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 effects of idebenone and alpha-tocopherol on beta-amyloid-(1-42)-induced learning and memory deficits in rats: implication of oxidative stress in beta-amyloid-induced neurotoxicity in vivo.

Amyloid beta-peptide (A beta), the major constituent of the senile plaques in the brains of patients with Alzheimer's disease, is cytotoxic to neurons and has a central role in the pathogenesis of the disease. Previous studies have suggested that oxidative stress is involved in the mechanisms of A beta-induced neurotoxicity in vitro. In the present study, we examined whether oxidative stress contributes to learning and memory deficits caused by continuous intracerebroventricular infusion of A beta-(1-42). In the A beta-(1-42)-infused rats, spontaneous alternation behaviour in a Y-maze and spatial memory in a water maze task were significantly impaired, as compared with A beta-(40-1)-infused control rats. The retention of passive avoidance learning was also significantly impaired by treatment with A beta-(1-42). Potent antioxidants idebenone and alpha-tocopherol prevented the behavioural deficits in Y-maze and water maze, but not passive avoidance, tasks in A beta-(1-42)-infused rats when they were repeatedly administered by mouth once a day from 3 days before the start of A beta infusion to the end of behavioural experiments. Lipid peroxide levels in the hippocampus and cerebral cortex of A beta-(1-42)-infused rats did not differ from those in control animals, and neither idebenone nor alpha-tocopherol affected the lipid peroxide levels. These results suggest that treatment with antioxidants such as idebenone and alpha-tocopherol prevents learning and memory deficits caused by A beta.

Ovariectomy potentiates β-amyloid-induced working memory deficits in rats

Ovariectomy potentiates β-amyloid-induced working memory deficits in rats

Concurrent activation of hippocampal glycine and polyamine sites of the N-methyl- d-aspartate receptor synergistically reverses working memory deficits in rats

Intrahippocampal administration of the non-competitive N-methyl- d-aspartate (NMDA) receptor antagonist MK-801 (0.18 μg/side) significantly increased the number of errors in the working memory task with a three-panel runway setup. The increase in working memory errors by intrahippocampal MK-801 was significantly attenuated by concurrent infusion of D-cycloserine (1.0 μg/side) or spermidine (10 μg/side), agonists of the glycine and polyamine modulatory sites on the NMDA receptor/channel complex, respectively. Combined injection of the behaviorally ineffective doses of 0.1 μg/side D-cycloserine and 0.32 μg/side spermidine synergistically reduced intrahippocampal MK-801-induced increase in working memory errors. The combination of D-cycloserine and spermidine also synergistically attenuated the increase in working memory errors resulting from intrahippocampal injection of the muscarinic acetylcholine receptor antagonist scopolamine (3.2 μg/side). These results suggest that positive modulation of the NMDA receptor/channel through activation of the glycine and polyamine sites can synergistically compensate deficiency of hippocampal NMDA and muscarinic receptor-mediated neurotransmission involved in working memory function.

Models of Dementia: Delayed Alternation in Aged Rats

Operant delayed alternation tasks are useful tools for assessing age-related memory deficits in rats. Decreased accuracy in these tasks seems to reflect mainly an inability to remember and utilize recent events (short-term memory deficit). The task described in this unit requires the rat to learn a delayed alternation for food reward in a standard Skinner box, so it must retain spatial information over a short period of time. Aged rats exhibit clear short-term memory impairments (decrease in response accuracy) in the task compared to young rats during learning and later, after extended training, also exhibit performance deficits. An advantage of studying these two phases is the possibility to examine either chronic effects (repeated drug administrations during acquisition) or acute effects (single treatments given before the test session during the stabilized performance phase). Operant delayed alternation tasks are useful tools for assessing age-related memory deficits in rats

σ Receptor ligands (+)-SKF10,047 and SA4503 improve dizocilpine-induced spatial memory deficits in rats

This study examined the effects of the σ receptor ligands (+)- N-allylnormetazocine ((+)-SKF10,047) and 1-(3,4-dimethoxyphenethyl)-4-(3-phenylpropyl)piperazine dihydrochloride (SA4503) on dizocilpine-induced impairment of working and reference memory in a radial arm maze task in rats. Dizocilpine, a non-competitive NMDA receptor antagonist, significantly impaired both reference and working memory, an effect which was accompanied by ataxia and impairment of food intake. The dizocilpine-induced impairment of reference memory was dose-dependently attenuated by (+)-SKF10,047 and SA4503. SA4503 also attenuated the dizocilpine-induced working memory impairment, although (+)-SKF10,047 had no effect. Neither σ receptor ligand affected the behavioral symptoms such as ataxia and impairment of food intake induced by dizocilpine. The ameliorating effects of both (+)-SKF10,047 and SA4503 on dizocilpine-induced spatial memory impairment were completely antagonized by a σ 1 receptor antagonist N, N-dipropyl-2-[4-methoxy-3-(2-phenylethoxy)phenyl]-ethylamine-monohydrochloride. These results suggest that the interaction of σ 1 receptors with NMDA receptors modulates spatial memory in rats.

FK960, a novel potential anti-dementia drug, augments long-term potentiation in mossy fiber-CA3 pathway of guinea-pig hippocampal slices

Our previous studies have demonstrated that FK960 (FR59960; N-(4-acetyl-1-piperazinyl)- p-fluorobenzamide monohydrate), a novel antidementia piperazine derivative, exerts beneficial effects on memory deficits in various animal models of amnesia in rats [M. Yamazaki, N. Matsuoka, N. Maeda, Y. Ohkubo, I. Yamaguchi, FK960 N-(4-acetyl-1-piperazinyl)- p-fluorobenzamide monohydrate ameliorates the memory deficits in rats through a novel mechanism of action, J. Pharmacol. Exp. Ther., 279 (1996) 1157–1173.] and in rhesus monkeys [N. Matsuoka, T.G. Aigner, FK960 [ N-(4-acetyl-1-piperazinyl)- p-fluorobenzamide monohydrate], a novel potential antidementia drug, improves visual recognition memory in rhesus monkeys: comparison with physostigmine, J. Pharmacol. Exp. Ther., 280 (1997) 1201–1209]. To clarify the synaptic mechanisms of its antiamnesic action, FK960 was investigated for its effects on the development of long-term potentiation (LTP) in guinea-pig hippocampal slices. The magnitude of LTP of population spike recorded in CA3 pyramidal neurons was significantly augmented by perfusing FK960 (10 −9–10 −6 M) for 25 min before and during tetanic stimulation of the mossy fibers, whereas the basal amplitude of population spikes before tetanus was hardly affected by the drug. The dose–response curve was bell-shaped with a maximal augmentation at 10 −7 M. Scopolamine (10 −6 M) per se had little effect on the magnitude of LTP in the mossy fiber-CA3 pathway, but significantly attenuated its enhancement by FK960 (10 −7 M). In hippocampal slices from animals treated with cysteamine (200 mg/kg, s.c.), which was shown to deplete the hippocampal somatostatin, FK960 (10 −7 M) hardly affected the LTP. These results suggest that FK960 enhances the magnitude of LTP in the mossy fiber-CA3 pathway through an activation of the cholinergic–somatostatinergic link in the hippocampal formation. Furthermore, it can be postulated that the drug regulates the cognitive function by modulating directly synaptic plasticity in the hippocampal neuronal network.

Propentofylline improves learning and memory deficits in rats induced by β-amyloid protein-(1-40)

We have reported that continuous infusion of β-amyloid protein-(1-40) into the cerebral ventricle produces learning and memory deficits in rats. Propentofylline has potent stimulatory effects on nerve growth factor (NGF) synthesis/secretion in mouse astrocytes in vitro and increases cerebral NGF content in aged rats. In the present study, we examined the effects of propentofylline on learning and memory deficits in β-amyloid protein-infused rats. The rats were given propentofylline orally once a day throughout the period of behavioral examination. In the β-amyloid protein-infused rats, spontaneous alternation behavior in a Y-maze, and performance in water maze and passive avoidance tasks were significantly impaired compared to sham-operated rats. Propentofylline prevented these behavioral deficits, but did not change the reduction of the activity of choline acetyltransferase in the hippocampus in the β-amyloid protein-infused rats. These results suggest that propentofylline is useful for the treatment of patients with Alzheimer's disease.

Moderate, long-term, alcohol consumption potentiates normal, age-related spatial memory deficits in rats.

A modified "Samson" sucrose fading procedure was used to establish voluntary consumption of a 20% ethanol (EtOH) solution in male Sprague-Dawley rats for 18 consecutive months. Intakes were stable over the life span, and corresponded to the moderate to high levels of intake typically observed in human "social" drinkers and alcoholics. The Morris Water Maze (WM), Olton Radial Arm Maze (RM), and a "balance beam" test were used to assess the effects of alcohol and aging on spatial memory and motor function. Aged EtOH-consuming rats (AGED/ALC) demonstrated impaired task acquisition, relative to aged controls (AGED), not reaching criterion performance in either spatial memory task even when given four additional days of training. AGED/ALC rats scored significantly lower on percent correct out of the first eight arm entries, and committed more perseverative errors in the RM. There were no significant performance differences between AGED and AGED/ALC rats on a balance beam test of fine motor coordination and equilibrium, suggesting that deficits observed in the RM and WM were not related to differential motor functioning. These results demonstrated that long-term, moderate, oral self-administration of EtOH, within the range typically consumed by humans, had adverse effects on spatial memory in rats, and that such a pattern of EtOH consumption seemed to exacerbate the decline in cognitive functioning associated with normal aging.

Reversal of scopolamine-induced deficits in radial maze performance by (−)-huperzine A: comparison with E2020 and tacrine

The effects of (−)-huperzine A ((5 R,9 R,11 E)-5-amino-11-ethylidene- 5,6,9,10-tetrahydro-7-methyl-5,9-methanocycloocta[ b]pyridin-2(1 H)-one), and of the hydrochloride salt of E2020 (( R, S)-1-benzyl-4-[(5,6-dimethoxy-1-indanon)-2-yl]-methyl piperidine) and tacrine (9-amino-1,2,3,4-tetrahydroacridine), on the scopolamine-induced memory deficits in rats were compared in a radial maze, using a 4-out-of-8 baiting procedure. Scopolamine (0.15 mg/kg, i.p.) caused significant impairment in the rats' ability to fulfil the radial maze task. (−)-Huperzine A (0.2–0.4 mg/kg, p.o.; 0.1–0.4 mg/kg, i.p.) had greater efficacy than E2020 (0.6–0.9 mg/kg, p.o.; 0.3–0.6 mg/kg, i.p.) and tacrine (1.5–2.5 mg/kg, p.o.; 0.3–0.6 mg/kg, i.p.) on the improvement of scopolamine-induced working and reference memory errors, respectively. There appeared to be an inverse bell-shape dose-dependent effect for all three compounds tested. The compared data demonstrate that (−)-huperzine A is the most potent and orally active acetylcholinesterase inhibitor of the three, and fits more closely the established criterions for an ideal acetylcholinesterase inhibitor to be used in clinical studies.

Effects of tacrine on deficits in active avoidance performance induced by AF64A in rats.

Effects of tacrine (1,2,3,4-tetrahydro-9-aminocridine) on memory deficits in rats treated with ethylcholine aziridinium ion (AF64A) were studied using active avoidance test in the two-way shuttle box. Neurotoxin AF64A injected at a dose of 6 nmol (i.c.v., bilaterally) causes nonspecific tissue damage in hippocampal fields CA2 and CA3. Two weeks after treatment with 6 nmol, AF64A active avoidance performance of toxin-treated rats was significantly deteriorated compared to vehicle-treated animals estimated in learning test (68 +/- 3.5 and 83 +/- 3.2% of correct responses, respectively; p < 0.01) and in retention test (53 +/- 5 and 76 +/- 3.6%, respectively; p < 0.01). Under these conditions, chronic treatment with tacrine at a daily dose of 1 mg/kg for 12-14 d reverses the effect of AF64A on the active avoidance performance both in learning (78 +/- 3.2%) and retention (72 +/- 4%) tests. It is supposed that behavioral effects of tacrine considerably depend on a severity of neurodegeneration in the hippocampus.

O-266 - FK960 ameliorates the memory deficits in rats through a novel mechanism of action

O-266 - FK960 ameliorates the memory deficits in rats through a novel mechanism of action

Dopamine and Spatial Working Memory in Rats and Monkeys: Pharmacological Reversal of Stress-Induced Impairment

The anxiogenic benzodiazepine inverse agonist FG7142 increases dopamine turnover in rodent prefrontal cortex but not in other dopamine terminal field areas. FG7142-induced increases in prefrontal cortical dopamine receptor stimulation impair prefrontal-dependent, but not nonprefrontal-dependent, cognitive tasks in rats and monkeys. The degree of impairment correlates with levels of prefrontal cortical dopamine turnover in rats and can be blocked in rats and monkeys with dopamine receptor antagonists, suggesting that increased dopamine turnover is directly related to the cognitive deficits. The current study examined nondopaminergic drug effects on FG7142-perturbed biochemistry and cognition. Both the noradrenergic alpha-2 agonist clonidine and the glycine/NMDA antagonist (+)HA966 prevented the FG7142-induced increase in dopamine turnover in rodent prefrontal cortex. Infusion of (+)HA966 into the ventral tegmental area (VTA) also blocked this increase in dopamine turnover, indicating that critical modulatory effects of (+)HA966 on FG7142-induced changes in dopamine turnover are occurring at the level of mesoprefrontal dopamine neuron cell bodies. Systemic (+)HA966 and clonidine, but not propranolol or D-cycloserine, prevented FG7142-associated spatial working memory deficits in rats and monkeys. These results support the idea of a critical range of dopamine turnover for optimal prefrontal cortical cognitive functioning, with excessive dopamine turnover leading to cognitive impairment. These studies also provide evidence for the regulation of prefrontal cortical dopamine turnover and cognition by multiple neurotransmitter systems and suggest that the VTA is an important regulatory site for these effects.

Fornix-fimbria section and working memory deficits in rats: Stimulus complexity and stimulus size.

Fornix-fimbria section and working memory deficits in rats: Stimulus complexity and stimulus size.