Serotonin synthesis inhibition in olivo-cerebellar system attenuates harmaline-induced tremor in Swiss albino mice

Mehta, Hina; Saravanan, K.; Mohanakumar, Kochupurackal P.

doi:10.1016/s0166-4328(03)00094-9

Cited by 33 publications

(12 citation statements)

References 25 publications

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“…A number of studies have suggested that activation of serotonergic system at the level of the inferior olive and the cerebellum was responsible for the aforementioned enhancement of the harmaline-induced tremor. Similar to the present study, harmaline reportedly increased the serotonin level in the cerebellum and inferior olive [26, 47, 48], while PCPA or serotonergic toxins decreased it [26], and reversed the harmaline-induced activation of climbing fibers [24]. Moreover, stimulation of 5-HT2A receptors in the inferior olive increased an average firing rate, rhythmicity, and synchronicity of complex spikes in Purkinje cells [49].…”

Section: Discussionsupporting

confidence: 79%

“…Such relationship has already been strongly suggested by others. It has been found that the inhibition of serotonin synthesis by systemic administration of p -chlorophenylalanine (PCPA—a tryptophan hydroxylase inhibitor [26]), or a lesion of serotonergic brain system induced by intraventricular 5,6- or 5,7-dihydroxytryptamine injections [24], decreased this symptom, whereas serotonin reuptake inhibitors (selective—citalopram, or non-selective—imipramine) enhanced it [47, 48]. A number of studies have suggested that activation of serotonergic system at the level of the inferior olive and the cerebellum was responsible for the aforementioned enhancement of the harmaline-induced tremor.…”

Section: Discussionmentioning

confidence: 99%

“…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%

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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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Section: Discussionsupporting

confidence: 79%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

et al. 2011

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“…On the other hand, electrophysiological evidence suggests that harmaline induced tremor by activating the inferior olivary nucleus and cerebellum DeMontigny and Lamarre, 1973;Mehta et al, 2003). It has also been demonstrated that harmaline blocks both associative and motor learning Welsh, 1998), although it is not known if this effect on learning and memory is mediated by the inferior olive or another area.…”

Section: Discussionmentioning

confidence: 99%

Effects of β-carboline alkaloids on the object recognition task in mice

et al. 2006

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“…The subtantia nigra (SN), nucleus accumbens (NAc), and nucleus raphe dorsalis (NRD) were micropunched from 1-mm frozen sections (Palkovits and Brownstein 1983). The tissues were processed for the analyses of the biogenic amine neurotransmitters and their metabolites employing an HPLC-electrochemical detection procedure (Mehta et al 2003;Muralikrishnan and Mohanakumar 1998). The tissues were sonicated in ice-cold 0.1 M HClO 4 containing 0.01% EDTA.…”

Section: Hplc Analysis Of Biogenic Aminesmentioning

confidence: 99%

Long-Term L-DOPA Treatment Causes Indiscriminate Increase in Dopamine Levels at the Cost of Serotonin Synthesis in Discrete Brain Regions of Rats

Borah

Mohanakumar

2007

Cell Mol Neurobiol

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(1) The treatment of choice for Parkinson's disease (PD) is 3,4-dihydroxyphenylalanine (L-DOPA) with peripheral decarboxylase inhibitor, but long-term therapy leads to motor and psychiatric complications. In the present study we investigated 5-hydroxytryptamine (5-HT) and dopamine concentrations in serotonergic and dopaminergic nuclei following chronic administration of L-DOPA to find whether the neurotransmitter synthesis in these brain areas are compensated. (2) Rats were administered L-DOPA (250 mg/kg) and carbidopa (25 mg/kg) daily for 59 and 60 days, and killed on the 60th day, respectively at 24 h and 30 min after the last dose. L-DOPA, norepinephrine, 5-HT, 5-hydroxyindoleacetic acid (5-HIAA), dopamine, homovanillic acid (HVA), and 3,4-dihydroxyphenylacetic acid (DOPAC) were measured in striatum, nucleus raphe dorsalis (NRD), nucleus accumbens (NAc), substantia nigra, cerebellum, and cortex employing HPLC-electrochemical procedure. (3) Prolonged treatment of L-DOPA caused depression in the animals as revealed in a forced swim test. Serotonin content was significantly decreased in all brain regions studied 30 min after long-term L-DOPA, except in NAc. The cortex and striatum showed lowered levels of this indoleamine 24 h after 59 doses of L-DOPA. Dopamine, HVA, and DOPAC concentrations were significantly higher in all the regions studied after 30 min, and in the cerebellum after 24 h of L-DOPA. The levels of DOPAC were elevated in all the brain areas studied 24 h after prolonged L-DOPA treatment. (4) The present results suggest that long-term L-DOPA treatment results in significant loss of 5-HT in serotonergic and dopaminergic regions of the brain. Furthermore, while L-DOPA metabolism per se was uninfluenced, dopamine synthesis was severely impaired in all the regions. The imbalance of serotonin and dopamine formation may be the cause of overt cognitive, motor, and psychological functional aberrations seen in parkinsonian patients following prolonged L-DOPA treatment.

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Serotonin synthesis inhibition in olivo-cerebellar system attenuates harmaline-induced tremor in Swiss albino mice

Cited by 33 publications

References 25 publications

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

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

Effects of β-carboline alkaloids on the object recognition task in mice

Long-Term L-DOPA Treatment Causes Indiscriminate Increase in Dopamine Levels at the Cost of Serotonin Synthesis in Discrete Brain Regions of Rats

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