Parenteral domoic acid impairs spatial learning in mice (original) (raw)
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Low Dose Domoic Acid Influences Spontaneous Behavior in Adult Rats
Physiological Research, 2014
Domoic acid (DA) is a potent marine neurotoxine present in seafood. Intoxication by DA causes gastrointestinal symptoms like vomiting and diarrhoea and also the so-called amnesic shellfish poisoning (inflicting memory impairment and seizures). Since exposure to non-convulsive doses is relevant to the human health, we investigated the effect of low dose DA administration in adult Wistar rats. Rats were administered with DA at the dose 1.0 mg/kg and their behavior was monitored for one hour in three sessions. The first session started immediately after DA administration. The second and third session started one and two weeks later. After the third session, the histochemical analysis of the hippocampi of the animals was conducted (Fluoro-Jade B, bis-benzimide). DA increased time spent by locomotion and distance travelled in the second half of the first session and this effect was pronounced during the second and third session. Exploratory rearing was decreased by DA administration in t...
Persistent changes in learning and memory in rats following neonatal treatment with domoic acid
Physiology & Behavior, 2009
The present study examined the effects of neonatal exposure to serial low dose injections of the glutamate agonist, domoic acid (DOM), on learning and memory in two spatial memory tasks in the rat. Neonatal Sprague Dawley rats were given single daily injections of low dose DOM (20 µg/kg) over postnatal days 8–14 and assessed as adolescents and adults in the radial 8-arm maze and the Morris Water Maze, respectively. Our results indicate that the DOM-treated rats showed a complex pattern of lasting alterations in learning and memory performance measures that were task specific. Adolescent DOM-treated animals, regardless of sex, demonstrated superior choice accuracy over seven days of testing in the 8-arm baited version of the radial maze. As adults, these same animals manifested improvements in several performance measures in the water maze. These improvements were also observed in a reversal task. However, when the escape platform was returned to its original position, some regression in search strategies were observed in the DOM-treated animals, especially the females, compared to their saline counterparts. These findings demonstrate that low-dose administration of a selective kainate receptor agonist during critical periods of CNS maturation produces lasting changes in learning and memory in the rat; adding to the ever-expanding body of literature which underscores the importance of optimal glutamatergic signaling to normal neurodevelopmental processes.
Brain Research, 1994
The relationship between hippocampal damage and spatial learning deficiencies was studied in rats injected with kainic acid (10 mg/kg i.p.). A single injection was given either before or after the acquisition phase of the Morris water-maze task. In this acquisition phase, the animals were required to find a hidden underwater platform starting from four different points. The task was repeated twice a day for 10 days. In the retention phase after 10 days rest, the rats repeated the same task. The damage caused by the treatment occurred in several prosencephalic areas, including the piriform and enthorhinal cortices, the thalamus and the hippocampus. In the latter, greatest damage was seen in CA1 followed by CA3 while CA2 and the gyrus dentatus appeared almost unaffected. The behavioural results indicated that kainic acid impaired but did not preclude the acquisition of the water-maze task. During the retention phase, no significant differences in latencies were found between animals that were treated before and after acquisition, thus, indicating that pretraining does not play an important role in the recovery of these spatial abilities following hippocampal lesions.
Vet Pathol Domoic: Brain Pathology in Adult Rats Treated With Domoic Acid
Domoic acid (DA) is a neurotoxin reported to produce damage to the hippocampus, which plays an important role in memory. The authors inoculated rats intraperitoneally with an effective toxic dose of DA to study the distribution of the toxin in major internal organs by using immunohistochemistry, as well as to evaluate the induced pathology by means of histopathologic and immunohistochemical methods at different time points after toxin administration (6, 10, and 24 hours; 5 and 54 days). DA was detected by immunohistochemistry exclusively in pyramidal neurons of the hippocampus at 6 and 10 hours after dosing. Lesions induced by DA were prominent at 5 days following treatment in selected regions of the brain: hippocampus, amygdala, piriform and perirhinal cortices, olfactory tubercle, septal nuclei, and thalamus. The authors found 2 types of lesions: delayed death of selective neurons and large areas of necrosis, both accompanied by astrocytosis and microgliosis. At 54 days after DA exposure, the pathology was characterized by still-distinguishable dying neurons, calcified lesions in the thalamus, persistent astrocytosis, and pronounced microgliosis. The expression of nitric oxide synthases suggests a role for nitric oxide in the pathogenesis of neuronal degeneration and chronic inflammation induced by DA in the brain.
Neural Toxicology and Pathology of Domoic Acid
Domoic acid is a potent neurotoxin when intake via contaminated seafood in bulk quantity, results in neural tissue necrosis. It caused an outbreak of human poisoning in Canada in 1987 by the consumption of contaminated blue mussels (Mytilus edulis), produced by red alga Chondria armataand and the genus Pseudo nitzschia. Domoic acid targets the glutamate receptors and the poisoning was characterized by memory impairment and brain disorders which led to the name Amnesic Shellfish Poisoning (ASP). Domoic acid has intoxicated wild animals and contaminated coastal waters since the 1987 incident. Hence it poses a global health and safety threat to significant human and wild animal lives populated at the shorelines. The present review aims to extend the understandings of ASP, DA induced toxicology and pathology which are critical for human health and wildlife safety.
Neurotoxicity Research, 2004
It is well established that the developing brain is a highly dynamic environment that is susceptible to toxicity produced by a number of pharmacological, chemical and environmental insults. We report herein on permanent behavioural and morphological changes produced by exposing newborn rats to very low (subconvulsive) doses of kainate receptor agonists during a critical window of brain development. Daily treatment of SD rat pups with either 5 or 20 µg/kg of domoic acid (DOM) from postnatal day 8-14 resulted in a permanent and reproducible seizure-like syndrome when animals were exposed to different tests of spatial cognition as adults. Similar results were obtained when animals were treated with equi-efficacious doses of kainic acid (KA; 25 or 100 µg/kg). Treated rats had significant increases in hippocampal mossy fiber staining and reductions in hippocampal cell counts consistent with effects seen in adult rats following acute injections of high doses of kainic acid.In situ hybridization also revealed an elevation in hippocampal brain derived neurotrophic factor (BDNF) mRNA in region CA1 without a corresponding increase in neuropeptide Y (NPY) mRNA. These results provide evidence of long-lasting behavioural and histochemical consequences arising from relatively subtle changes in glutamatergic activity during development, that may be relevant to understanding the aetiology of seizure disorders and other forms of neurological disease.
Effects of a Single Intraseptal Injection of NGF on Spatial Learning in the Water Maze
Physiology & Behavior, 1997
Effects of a single intraseptal injection of NGF on spatial learning in the water maze. PHYSIOL BEHAV 62(1) [69][70][71][72][73][74][75][76] 1997.-Male Sprague-Dawley rats given electrolytic lesions of the septum followed by a single intraseptal injection of 5 mg of NGF were trained on a water maze task that assessed their ability to learn the location of a visible platform and the location of platform when it was submerged. Rats with damage to the septum acquired the visible platform version of the task but were significantly impaired in locating the submerged platform. Administration of NGF, however, produced an intermediate ameliorative effect on the measure of latency to find the hidden platform during these trials. In order to determine the relative strength of the place and cue responses learned during the visible and hidden platform training trials, a probe trial was given on the final test day in which the visible platform was moved to a new location. Control rats swam either to the new platform location or the old platform location indicating the use of both a place and cue response. However, both rats with septal damage alone and rats with septal lesions treated with NGF swam directly to the new platform location indicating the relative strength of the cue response. These results support previous findings indicating that a single injection of NGF can produce improvements on a cognitive task, but it may not be doing so by restoring lost spatial functions following septohippocampal damage. ᭧ 1997 Elsevier Science Inc.
Domoic acid-induced neurotoxicity in the hippocampus of adult rats
Neurotoxicity Research, 2004
Domoic acid (DA), an agonist of non-N-methyl-D-aspartate (non-NMDA) receptor subtype including kainate receptor, was identified as a potent neurotoxin showing involvement in neuropathological processes like neuronal degeneration and atrophy. In the past decade evidence indicating a role for excitatory amino acids in association with neurological disorders has been accumulating. Although the mechanisms underlying the neuronal damage induced by DA are not yet fully understood, many intracellular processes are thought to contribute towards DA-induced excitotoxic injury, acting in combination leading to cell death. In this review article, we report the leading hypotheses in the understanding of DA-induced neurotoxicity, which focus on the role of DA in neuropathological manifestations, the formation of the retrograde messenger molecule nitric oxide (NO) for the production of free radicals in the development of neuronal damage, the activation of glial cells (microglia and astrocytes) in response to DA-induced neuronal damage and the neuroprotective role of melatonin as a free radical scavenger or antioxidant in DA-induced neurotoxicity. The possible implications of molecular mechanism underlying the neurotoxicity in association with necrosis, apoptosis, nitric oxide synthases (nNOS and iNOS) and glutamate receptors (NMDAR1 and GluR2) related genes and their expression in DA-induced neuronal damage in the hippocampus have been discussed.
Frontiers in Behavioral Neuroscience, 2014
The dorsal striatum is involved in cue-based navigation strategies and in the development of habits. It has been proposed that striatum-dependent cued navigation competes with hippocampus-dependent spatial navigation in some circumstances. We have previously shown that large lesions of the dorsal striatum, as well as impairment of corticostriatal synaptic plasticity in transgenic mice, can enhance spatial learning in a water maze task, presumably by the disruption of competitive interference. However, the dorsal striatum is not a homogeneous structure; both anatomical considerations and experimental studies in various paradigms show that dorsomedial and dorsolateral striatum are functionally distinct, although there is no precise anatomical or neurochemical boundary between them. Here we investigated the effect of restricted excitotoxic lesions of dorsomedial striatum (DMS) on cued and spatial water maze learning. We find that dorsomedial striatal lesions delay spatial learning but permit cued learning. After cued learning, lesioned animals showed inflexible search, resulting in repeated visits to the escape platform-associated cue. These results support a role for the DMS in behavioral flexibility rather than in cue-based navigation.