Ibotenic acid lesions

Dunnett SB, Lane DM, Winn P (1985) Ibotenic acid lesions of the lateral hypothalamus comparison with 6-hydroxydopamine induced sensorimotor deficits. Neuroscience 74 509-518. 

KD, Mishkin M (1991) Transient impairment of recognition memory following ibotenic-acid lesions of the basal forebrain in macaques. Exp Brain Res 86 18-26... 

Ridley RM, Baker HF, Drewett B, Johnson JA (1985) Effects of ibotenic acid lesions of the basal forebrain on serial reversal learning in marmosets. Psychopharmacology (Berl) 86 438 43... 

Touzani K, Velley L. 1990. Ibotenic acid lesion of the lateral hypothalamus increases preference and aversion thresholds for saccharin and alters the morphine modulation of taste. Pharmacol Biochem Behav 36 585-591. 

Garvey, L. J., and Hornung, J. P., 1980, The use of ibotenic acid lesions for light and electron microscopy study of anterograde degeneration in the visual pathway of the cat, Neurosci. Lett. 19 117—123. 

Little is formally known about the toxicity of amanita use. Ibotenic acid is a potent neurotoxin, through excitatory amino acid mechanisms (Steiner et al. 1984 Schwarcz et al. 1984). It has been used extensively in animal research to create discrete neuroanatomical lesions. For example, it has been used to lesion the basal forebrain nuclei to create a putative animal model of Alzheimer s disease (Arbogast and Kozlowski 1988). 

Lesioned animal models are based upon the assumption that the destruction of basal forebrain cholinergic neurons by injection of a neurotoxin, such as ibotenic acid, is sufficient to reproduce some of the cognitive impairments associated with AD, mainly memory and learning deficits. Indeed, pathology in the basal forebrain... 

Robbins. T. W., Everitt, B. J., Mar.ston, H, M, Wilkinson, J., Jones, G. H., and Page, K, I. (1989). Comparative effects of ibotenic acid- and qui.squalic acid-induced lesions of the substantia innomiiiata on attcntional function in the rat Further implications for the role of the cholinergic neurons of the iiucleu.s basalis in cogniUve processes, Behav. Brain Res. 35, 221-240. 

Coyle et aL, 1981). For example, ibotenic acid in doses of 10-20 nmol causes an extensive lesion of the injected hippocampal formation without causing seizures, whereas 140 nmol of iV-methyl-D-aspartate precipitates severe seizures but causes small lesions restricted to the hippocampal formation. Nevertheless, the convulsant and neurotoxic properties of kainic acid, at least within the limbic system, suggest that kainate may prove to be a particularly useful agent for probing basic mechanisms involved in epilepsy. 

In comparative studies of the neurotoxic effects of NMDA and kainic acid in the hippocampal formation, we have found that NMDA is approximately 100-fold less potent as a neurotoxin than kainic acid on a molar basis (Zaczek et aL, 1981). The lesion associated with local injection of NMDA is limited to the injection site in the hippocampal formation and appears to uniformly affect all neuronal perikarya within its circumference. However, doses of NMDA effective in causing significant lesions in the dentate gyrus precipitated a severe electroencephalographic and behavioral seizure disturbance punctuated by frequent tonic-clonic convulsions occasionally resulting in death. Thus, the superiority of NMDA over kainic acid and ibotenic acid for intracerebral injection remains to be established. 

The maturity of brain plays an important role in neuronal vulnerability to excitotoxins. The CVO regions and neural retina of immature rats and mice (less than 10 days of age) are much more sensitive to peripherally administered excitotoxins than the adult. In contrast, the striatum of the neonatal rat is remarkably resistant to doses of kainic acid that produce extensive lesions in the adult but full vulnerability is attained by three weeks after birth (Campochiaro and Coyle, 1978). Similarly, Honnegar and Richelson (1977) have found that reaggregating brain cultures exhibit increasing sensitivity to the neurotoxic effects of kainic acid with differentiation. At the other extreme, neuronal sensitivity of the striatum to directly injected kainate appears to increase with advancing age (Gaddy et aL, 1979). An age dependence for the neurotoxic action of ibotenic acid and other directly injected excitotoxins has not yet been described. 

In a second paper Baunez et al. (1995) produced dopamine depletion in rats by infusing the neurotoxin 6-hydroxydopamine (6-OHDA) bilaterally into the dorsal part of the striatum. They found an increase in the number of delayed responses and a lengthening of RTs. Lesions of the subthalamic nucleus with ibotenic acid induced the opposite increase in the number of premature responses and a decrease of RTs. 

Moreover, there are similarities between the behavioural changes following lead exposure and those seen after hippocampal damage (Alfano and Petit, 1981). Therefore, a direct comparison between lesioned animals and lead-exposed ones is desirable. For this purpose ibotenic acid, an excitotoxin, was used to induce chemical lesions of intrinsic neurons to the hippocampus only, while fibres of passage and afferents were spared. Lesioned animals were compared with animals exposed to low levels of lead. 

For surgery 20 control females were anaesthetized at the age of 165 days with an intraperitoneal injection of 45 mg/kg of ketamine. Ibotenic acid (IBO) was stereotaxically injected into the dorsal hippocampi (10 jUg IBO in 0.5 jul of phosphate buffer into each hemisphere). Ten additional females were treated alike without IBO injection (sham operation). For amygdala lesions 0.4 jUg IBO in 0.4 jul phosphate buffer were stereotaxically injected into each side. 

The impaired performance of lead-exposed rats during acquisition of spatial learning agrees with former observations at much higher levels of exposure (Alfano and Petit 1981). This lead-induced deficit does not resemble effects of chemical lesions of the hippocampus with ibotenic acid. Unlike lead-exposed animals, those with hippocampal depletion took less time than controls to make eight correct choices. Thus chemical lesions of the hippocampus, in contrast to mechanical ones, fail to impair spatial learning. This outcome is in accordance with previous results (Jarrard, 1983 Jarrard et al 1984). 

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