Lu AF21934, a positive allosteric modulator of mGlu4 receptors, reduces the harmaline-induced hyperactivity but not tremor in rats

Ossowska, Krystyna; Wardas, Jadwiga; Berghauzen-Maciejewska, Klemencja; Głowacka, Urszula; Kuter, Katarzyna; Pilc, Andrzej; Zorn, Stevin H.; Doller, Darı́o

doi:10.1016/j.neuropharm.2014.03.018

Cited by 15 publications

(21 citation statements)

References 52 publications

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“…As observed earlier [19,[24][25][26]28], the harmaline induced tremor was evidenced by increases in the tremor index and AP2 (Figs. 1, 2 and 4).…”

Section: The Harmaline-induced Tremorsupporting

confidence: 79%

“…The peak frequency of the harmaline-induced tremor in rats is 10-12 Hz [4,19,24]. Accordingly, in the present study, power in the 9-15 Hz band (AP2) was increased in the harmaline-treated animals and was associated with an increase in the tremor index [a difference between the power AP2 and that in the 0-8 band (AP1)].…”

Section: Discussionsupporting

confidence: 48%

“…Control animals received physiological saline twice instead of harmaline, propranolol or apomorphine. A dose of harmaline (15 mg/kg) was used following our recent paper [19], which showed that this dose induced marked tremor in rats, as measured by the force plate actimeters. The doses of apomorphine (0.5 and 1 mg/kg) and propranolol (20 mg/kg) were chosen according to previous studies that characterized their effectiveness in harmaline-induced tremor in rodents [2,3].…”

Section: Drugsmentioning

confidence: 99%

“…For example, we recently found, using fully automatic force plate actimeters, that in addition to tremor, harmaline induces delayed general hyperactivity (bouts of low mobility, increased basic activity) [19], which might interfere with the scoring of tremor intensity. Therefore, in the present study we used a similar approach to re-examine the influence of apomorphine on the harmaline-induced tremor in rats while simultaneously measuring locomotor activity and stereotypy.…”

Section: Introductionmentioning

confidence: 99%

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Apomorphine enhances harmaline-induced tremor in rats

Ossowska

Głowacka

Kosmowska

et al. 2015

Pharmacological Reports

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“…As observed earlier [19,[24][25][26]28], the harmaline induced tremor was evidenced by increases in the tremor index and AP2 (Figs. 1, 2 and 4).…”

Section: The Harmaline-induced Tremorsupporting

confidence: 79%

Section: Discussionsupporting

confidence: 48%

Section: Drugsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Apomorphine enhances harmaline-induced tremor in rats

Ossowska

Głowacka

Kosmowska

et al. 2015

Pharmacological Reports

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“…In addition, high dose combinations of harmaline (5 or 15 mg/kg) and 5-MeO-DMT (10 mg/kg) obviously induced serotonin toxicity (CBT > 39 °C) in mouse models (Isbister and Buckley, 2005). Harmaline not only increases 5-HT levels through inhibition of MAO-A activity (Cheng et al, 2013; Kim et al, 1997) but also binds to multiple neurotransmitter receptors such as 5-HT, norepinephrine, dopamine D 2 /D 3 and N -methyl-D-aspartate (NMDA) glutamate receptors (Airaksinen et al, 1987; Iseri et al, 2011; Miralles et al, 2005; Ossowska et al, 2014; Paterson et al, 2009) that may all affect thermoregulation. Therefore, the potentiation of hyperthermia and induction of serotonin toxicity by co-administration of harmaline with 5-MeO-DMT could be mechanistically due to the alteration of 5-MeO-DMT pharmacokinetics (Jiang et al, 2013), inhibition of MAO-A and binding of various neurotransmitter receptors.…”

Section: Discussionmentioning

confidence: 99%

Potentiation of 5-methoxy-N,N-dimethyltryptamine-induced hyperthermia by harmaline and the involvement of activation of 5-HT1A and 5-HT2A receptors

Jiang

Shen

2015

Neuropharmacology

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5-Methoxy-N,N-dimethyltryptamine (5-MeO-DMT) and harmaline are serotonin (5-HT) analogs often abused together, which alters thermoregulation that may indicate the severity of serotonin toxicity. Our recent studies have revealed that co-administration of monoamine oxidase inhibitor harmaline leads to greater and prolonged exposure to 5-HT agonist 5-MeO-DMT that might be influenced by cytochrome P450 2D6 (CYP2D6) status. This study was to define the effects of harmaline and 5-MeO-DMT on thermoregulation in wild-type and CYP2D6-humanized (Tg-CYP2D6) mice, as well as the involvement of 5-HT receptors. Animal core body temperatures were monitored noninvasively in the home cages after implantation of telemetry transmitters and administration of drugs. Harmaline (5 and 15 mg/kg, i.p.) alone was shown to induce hypothermia that was significantly affected by CYP2D6 status. In contrast, higher doses of 5-MeO-DMT (10 and 20 mg/kg) alone caused hyperthermia. Co-administration of harmaline (2, 5 or 15 mg/kg) remarkably potentiated the hyperthermia elicited by 5-MeO-DMT (2 or 10 mg/kg), which might be influenced by CYP2D6 status at certain dose combination. Interestingly, harmaline-induced hypothermia was only attenuated by 5-HT1A receptor antagonist WAY-100635, whereas 5-MeO-DMT- and harmaline-5-MeO-DMT-induced hyperthermia could be suppressed by either WAY-100635 or 5-HT2A receptor antagonists (MDL-100907 and ketanserin). Moreover, stress-induced hyperthermia under home cage conditions was not affected by WAY-100635 but surprisingly attenuated by MDL-100907 and ketanserin. Our results indicate that co-administration of monoamine oxidase inhibitor largely potentiates 5-MeO-DMT-induced hyperthermia that involves the activation of both 5-HT1A and 5-HT2A receptors. These findings shall provide insights into development of anxiolytic drugs and new strategies to relieve the lethal hyperthermia in serotonin toxicity.

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Pramipexole Reduces zif-268 mRNA Expression in Brain Structures involved in the Generation of Harmaline-Induced Tremor

2020

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Essential tremor is one of the most common neurological disorders, however, it is not sufficiently controlled with currently available pharmacotherapy. Our recent study has shown that pramipexole, a drug efficient in inhibiting parkinsonian tremor, reduced the harmaline-induced tremor in rats, generally accepted to be a model of essential tremor. The aim of the present study was to investigate brain targets for the tremorolytic effect of pramipexole by determination of the early activitydependent gene zif-268 mRNA expression. Tremor in rats was induced by harmaline administered at a dose of 15 mg/kg ip. Pramipexole was administered at a low dose of 0.1 mg/kg sc. Tremor was measured by Force Plate Actimeters where four force transducers located below the corners of the plate tracked the animal's position on a Cartesian plane. The zif-268 mRNA expression was analyzed by in situ hybridization in brain slices. Harmaline induced tremor and increased zif-268 mRNA levels in the inferior olive, cerebellar cortex, ventroanterior/ventrolateral thalamic nuclei and motor cortex. Pramipexole reversed both the harmaline-induced tremor and the increase in zif-268 mRNA expression in the inferior olive, cerebellar cortex and motor cortex. Moreover, the tremor intensity correlated positively with zif-268 mRNA expression in the above structures. The present results seem to suggest that the tremorolytic effect of pramipexole is related to the modulation of the harmaline-increased neuronal activity in the tremor network which includes the inferior olive, cerebellar cortex and motor cortex. Potential mechanisms underlying the above pramipexole action are discussed.

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Lu AF21934, a positive allosteric modulator of mGlu4 receptors, reduces the harmaline-induced hyperactivity but not tremor in rats

Cited by 15 publications

References 52 publications

Apomorphine enhances harmaline-induced tremor in rats

Apomorphine enhances harmaline-induced tremor in rats

Potentiation of 5-methoxy-N,N-dimethyltryptamine-induced hyperthermia by harmaline and the involvement of activation of 5-HT1A and 5-HT2A receptors

Pramipexole Reduces zif-268 mRNA Expression in Brain Structures involved in the Generation of Harmaline-Induced Tremor

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