Differential expression of c-Fos following administration of two tremorgenic agents

Miwa, Hideto; Nishi, Katsunori; Fuwa, Tatsu; Mizuno, Yoshikuni

doi:10.1097/00001756-200008030-00010

Cited by 48 publications

(17 citation statements)

References 7 publications

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“…Studies of animal models of tremor have reported wide-spread, or even global, rhythmic oscillations (at 8-12 Hz) among inferior olive neurons induced by harmaline (De and Lamarre, 1973; Batini et al , 1979; Bernard et al , 1984; Miwa et al , 2000). Yet, harmaline does not induce OPT (Kane and Thach, 1989).…”

Section: Discussionmentioning

confidence: 99%

Oculopalatal tremor explained by a model of inferior olivary hypertrophy and cerebellar plasticity

Shaikh

Hong

Liao

et al. 2010

Brain

150

147

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The inferior olivary nuclei clearly play a role in creating oculopalatal tremor, but the exact mechanism is unknown. Oculopalatal tremor develops some time after a lesion in the brain that interrupts inhibition of the inferior olive by the deep cerebellar nuclei. Over time the inferior olive gradually becomes hypertrophic and its neurons enlarge developing abnormal soma-somatic gap junctions. However, results from several experimental studies have confounded the issue because they seem inconsistent with a role for the inferior olive in oculopalatal tremor, or because they ascribe the tremor to other brain areas. Here we look at 3D binocular eye movements in 15 oculopalatal tremor patients and compare their behaviour to the output of our recent mathematical model of oculopalatal tremor. This model has two mechanisms that interact to create oculopalatal tremor: an oscillator in the inferior olive and a modulator in the cerebellum. Here we show that this dual mechanism model can reproduce the basic features of oculopalatal tremor and plausibly refute the confounding experimental results. Oscillations in all patients and simulations were aperiodic, with a complicated frequency spectrum showing dominant components from 1 to 3 Hz. The model’s synchronized inferior olive output was too small to induce noticeable ocular oscillations, requiring amplification by the cerebellar cortex. Simulations show that reducing the influence of the cerebellar cortex on the oculomotor pathway reduces the amplitude of ocular tremor, makes it more periodic and pulse-like, but leaves its frequency unchanged. Reducing the coupling among cells in the inferior olive decreases the oscillation’s amplitude until they stop (at ∼20% of full coupling strength), but does not change their frequency. The dual-mechanism model accounts for many of the properties of oculopalatal tremor. Simulations suggest that drug therapies designed to reduce electrotonic coupling within the inferior olive or reduce the disinhibition of the cerebellar cortex on the deep cerebellar nuclei could treat oculopalatal tremor. We conclude that oculopalatal tremor oscillations originate in the hypertrophic inferior olive and are amplified by learning in the cerebellum.

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Section: Discussionmentioning

confidence: 99%

Oculopalatal tremor explained by a model of inferior olivary hypertrophy and cerebellar plasticity

Shaikh

Hong

Liao

et al. 2010

Brain

150

147

View full text Add to dashboard Cite

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“…Furthermore, 5-HT can cross-regulate acetylcholine release in the brain (Jackson et al, 1988; Jäkälä et al, 1992; Sparks et al, 2018) and harmaline also binds to other neurotransmitter receptors (norepinephrine, dopamine, glutamate receptors; Glennon et al, 2000; Miwa et al, 2000; Grella et al, 2003; Beitz and Saxon, 2004; Kralic et al, 2005; Paterson et al, 2009) This whole excessive alteration of the neurotransmitter systems may be related in the present data to decreased attention and learning observed after chronic Ayahuasca exposure. In fact, both chronic groups C0.1 and C0.5 presented reduced exploration time, and discrimination index significantly inferior to the control and acute groups.…”

Section: Discussionmentioning

confidence: 99%

It’s Tea Time: Interference of Ayahuasca Brew on Discriminative Learning in Zebrafish

Lobão-Soares

Eduardo-da-Silva

Amarilha

et al. 2018

Front. Behav. Neurosci.

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Ayahuasca is a psychoactive brew traditionally used in shamanistic and vegetalistic rituals and has recently received lot of attention due to potential cognitive benefits. Ayahuasca effects are caused by the synergistic interaction of β-carbolines (harmine, harmaline and tetrahydroarmine) contained in Banisteriopsis caapi stalks combined with the N,N-dimethyltryptamine (DMT) from Psychotria viridis leaves, a potent agonist to serotonin (5-HT) receptors. The present study approaches the effects of chronic and acute exposure to two Ayahuasca concentrations (0.1 and 0.5 ml/L) on the cognitive ability to discriminate objects in a one-trial learning task in zebrafish. Based on the combination of concentrations and exposure regimens, we divided adult zebrafish in five treatment groups: acute 0.1 and 0.5 ml/L, chronic 0.1 and 0.5 ml/L, and control 0.0 (n = 20 for each group). Then we tested them in a memory task of object discrimination. Acute Ayahuasca exposed groups performed similarly to the control group, however chronically treated fish (13 days) presented both impaired discriminative performance and locomotor alterations. Overall, these results indicate that Ayahuasca is a potent psychoactive drug that, in chronic exposure, negatively affects mnemonic parameters in zebrafish. In single exposure it does not affects cognitive performance, but the higher concentration (0.5) affected locomotion. Moreover, we reinforce the importance of the zebrafish for behavioral pharmacological studies of drug screening, in special to psychedelic drug research.

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“…Oscillation frequency in this tremor decreases with increasing weight of an animal and is equal to 11–14 Hz in mice, 10–12 Hz in rats, and 8–10 Hz in monkeys [18]. Although a synchronous activation of the olivo-cerebellar pathway and release of glutamate in the cerebellum which acts at NMDA and AMPA receptors has been suggested to be a primary cause of the harmaline-induced tremor [18, 22, 23], the mechanisms underlying this symptom seem to be complex and may involve also noradrenergic, serotonergic, dopaminergic, and GABA-ergic systems [23–26], as well as some distant brain structures, e.g., reticular formation, caudate–putamen, frontal cortex, and others [27–29]. The latter assumption is based on the fact that a systemic harmaline administration in tremorgenic doses induces metabolic and neuronal activation in the above structures [27–29].…”

Section: Introductionmentioning

confidence: 99%

“…Although a synchronous activation of the olivo-cerebellar pathway and release of glutamate in the cerebellum which acts at NMDA and AMPA receptors has been suggested to be a primary cause of the harmaline-induced tremor [18, 22, 23], the mechanisms underlying this symptom seem to be complex and may involve also noradrenergic, serotonergic, dopaminergic, and GABA-ergic systems [23–26], as well as some distant brain structures, e.g., reticular formation, caudate–putamen, frontal cortex, and others [27–29]. The latter assumption is based on the fact that a systemic harmaline administration in tremorgenic doses induces metabolic and neuronal activation in the above structures [27–29]. Moreover, since harmaline has been found to modulate postural tremor induced by a lesion of the substantia nigra in monkeys [30], some interrelationship between neuronal alterations triggered by harmaline and those underlying tremor induced by degeneration of dopaminergic neurons may be suggested.…”

Section: Introductionmentioning

confidence: 99%

Lesion of the Cerebellar Noradrenergic Innervation Enhances the Harmaline-Induced Tremor in Rats

et al. 2011

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Abnormal synchronous activation of the glutamatergic olivo-cerebellar pathway has been suggested to be crucial for the harmaline-induced tremor. The cerebellum receives two catecholaminergic pathways: the dopaminergic pathway arising from the ventral tegmental area/substantia nigra pars compacta, and the noradrenergic one from the locus coeruleus. The aim of the present study was to examine a contribution of the cerebellar catecholaminergic innervations to the harmaline-induced tremor in rats. Rats were injected bilaterally into the cerebellar vermis with 6-hydroxydopamine (6-OHDA; 8 μg/0.5 μl) either alone or this treatment was preceded (30 min earlier) by desipramine (15 mg/kg ip). Harmaline was administered to animals in doses of 7.5 or 15 mg/kg ip. Tremor of forelimbs was measured as a number of episodes during a 90-min observation. Rats were killed by decapitation 30 or 120 min after harmaline treatment. The levels of dopamine, noradrenaline, serotonin, and their metabolites were measured by HPLC in the cerebellum, substantia nigra, caudate–putamen, and frontal cortex. 6-OHDA injected alone enhanced the harmaline-induced tremor. Furthermore, it decreased the noradrenaline level by ca. 40–80% in the cerebellum and increased the levels of serotonin and 5-HIAA in the caudate–putamen and frontal cortex in untreated and/or harmaline-treated animals. When 6-OHDA treatment was preceded by desipramine, it decreased dopaminergic transmission in some regions of the cerebellum while inducing its compensatory activation in others. The latter lesion did not markedly influence the tremor induced by harmaline. The present study indicates that noradrenergic innervation of the cerebellum interacts with cerebral serotonergic systems and plays an inhibitory role in the harmaline-induced tremor.

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Differential expression of c-Fos following administration of two tremorgenic agents

Cited by 48 publications

References 7 publications

Oculopalatal tremor explained by a model of inferior olivary hypertrophy and cerebellar plasticity

Oculopalatal tremor explained by a model of inferior olivary hypertrophy and cerebellar plasticity

It’s Tea Time: Interference of Ayahuasca Brew on Discriminative Learning in Zebrafish

Lesion of the Cerebellar Noradrenergic Innervation Enhances the Harmaline-Induced Tremor in Rats

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