Evidence map›Paper›PMID 41137941›Full record

ArticlePsychopharmacology2026

Haloperidol - norepinephrine synergy in stimulation of vacuous chewing movements in rats: Enhancement by nicotine.

Ilya D Ionov, Maria D Krasilova, Niсholas P Gorev, Victor I Tulchinskiy, Sergey A Gabov, Margarita O Lyubimova, Lyudmila I Maltseva, Piotr N Komikarov

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Article in Psychopharmacology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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5 · Who and what money

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8 authors.

Ilya D IonovDepartment of Neurometabolic Analysis, Centre on Theoretical Problems in Physical and Chemical Pharmacology, Russian Academy of Sciences, Srednyaya Kalitnikovskaya 30, Moscow, 109029, Russia. newrology@yandex.ru.ORCID http://orcid.org/0000-0002-1556-6707
Maria D KrasilovaDepartment of Neurometabolic Analysis, Centre on Theoretical Problems in Physical and Chemical Pharmacology, Russian Academy of Sciences, Srednyaya Kalitnikovskaya 30, Moscow, 109029, Russia.
Niсholas P GorevDepartment of Neurometabolic Analysis, Centre on Theoretical Problems in Physical and Chemical Pharmacology, Russian Academy of Sciences, Srednyaya Kalitnikovskaya 30, Moscow, 109029, Russia.
Victor I TulchinskiyDepartment of Neurometabolic Analysis, Centre on Theoretical Problems in Physical and Chemical Pharmacology, Russian Academy of Sciences, Srednyaya Kalitnikovskaya 30, Moscow, 109029, Russia.
Sergey A GabovDepartment of Neurometabolic Analysis, Centre on Theoretical Problems in Physical and Chemical Pharmacology, Russian Academy of Sciences, Srednyaya Kalitnikovskaya 30, Moscow, 109029, Russia.
Margarita O LyubimovaDepartment of Neurometabolic Analysis, Centre on Theoretical Problems in Physical and Chemical Pharmacology, Russian Academy of Sciences, Srednyaya Kalitnikovskaya 30, Moscow, 109029, Russia.
Lyudmila I MaltsevaDepartment of Neurometabolic Analysis, Centre on Theoretical Problems in Physical and Chemical Pharmacology, Russian Academy of Sciences, Srednyaya Kalitnikovskaya 30, Moscow, 109029, Russia.
Piotr N KomikarovTimpharm LTD, Moscow, 117513, Russia.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

rationaleTardive dyskinesia (TD), a late onset involuntary repetitive movements, is a complication of antipsychotic therapy. The mechanism of TD development is currently obscure. In TD patients, an increased brain level of norepinephrine was found; the pathogenic significance of this abnormality is unclear. The chronic administration of haloperidol in rodents induces a specific stereotyped behavior called vacuous chewing movements (VCM) that resembles TD and is used as a routine TD model. Meanwhile, this model does not mirror such a feature of TD as an exacerbation by tobacco smoking.

objectivesWe examined the hypotheses that (i) sustained brain norepinephrine hyperactivity influences the development of haloperidol-induced VCM; and (ii) VCM induced by haloperidol-norepinephrine combination, are enhanced by nicotine.

methodsMale Sprague-Dawley rats were used. VCM were exerted by 25-day administration of haloperidol; to simulate an increase in brain norepinephrine levels this agent was injected intracerebroventricularly for 14 consecutive days. Nicotine was given daily concurrently with norepinephrine.

resultsSeparated administration of haloperidol and norepinephrine at low doses resulted in no effect; however, their co-administration induced a clear stimulation of VCM. The chronic nicotine treatment did not affect the haloperidol-induced VCM but strongly enhanced the effect induced by the haloperidol + norepinephrine combination.

conclusionsIt was found for the first time that haloperidol and norepinephrine synergistically stimulate VCM; this finding can advance our understanding of TD pathogenesis. In the light of these results, norepinephrine may be a promising therapeutic target in TD. Given the obtained results, the haloperidol + norepinephrine-induced VCM seem to be more reasonable model for TD than haloperidol-only one.

Indexed as

Antipsychotic AgentsHaloperidolMasticationNicotineNicotinic AgonistsNorepinephrineTardive DyskinesiaAnimalsDisease Models, AnimalDose-Response Relationship, DrugDrug SynergismInjections, IntraventricularMaleRatsRats, Sprague-DawleyAntipsychotic AgentsHaloperidolNicotineNicotinic AgonistsNorepinephrineHaloperidolNicotineNorepinephrineSynergyTardive dyskinesiaVacuous chewing movements

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.