Abstract
Rationale
Recently, it was found that cyclosomatostatin-induced catalepsy in middle-aged rats is accompanied by neuronal hypoactivation in the lateral entorhinal cortex (LEntCx); this hypoactivation was reversed by systemic administration of nicotine combined with diphenhydramine. These findings suggest the ability of nicotine to regulate catalepsy and the involvement of the LEntCx in this nicotine effect.
Objectives
The study was aimed to assess whether nicotine alone influences catalepsy when injected into the LEntCx and some other neuroanatomical structures.
Methods
Experiments were conducted with male Wistar rats of 540–560 days of age. Catalepsy was induced by intracerebroventricular injection of cyclosomatostatin and assessed by the standard bar test. Nicotine was injected into the LEntCx, prelimbic cortex (PrCx), or basolateral amygdala (BLA). The tissue levels of tyrosine hydroxylase, dopamine, and DOPAC in the substantia nigra pars compacta and dorsal striatum were measured with use of HPLC and ELISA.
Results
Injections of nicotine into the LEntCx but not into the PrCx and BLA produced anticataleptic effect; the nicotine effect was significantly reversed by intra-LEntCx administration of NMDA and non-NMDA glutamate receptor antagonists. Nicotine also attenuated cataleptogen-induced changes in nigrostriatal dopamine metabolism.
Conclusions
This may be the first demonstration of anticataleptic activity of nicotine. The results show that the effect is mediated by nicotine receptors in the LEntCx, via a glutamatergic mechanism. These findings may help advance the development of novel treatments for extrapyramidal disorders, including parkinsonism.
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Change history
21 May 2022
An Editorial Expression of Concern to this paper has been published: https://doi.org/10.1007/s00213-022-06168-8
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Acknowledgements
I.D.I. is indebted to his long-standing mentors, late Prof. Igor Efimovich Kovalev and late Prof. Lev Aramovich Piruzyan. Technical support of this research by “Timpharm Ltd.” (Moscow, Russia) is highly appreciated.
Funding
The study was supported by the Ministry of Science and Higher Education of the Russian Federation (project AAAA-A18-118012390247–0).
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Ionov, I.D., Pushinskaya, I.I., Gorev, N.P. et al. Anticataleptic activity of nicotine in rats: involvement of the lateral entorhinal cortex. Psychopharmacology 238, 2471–2483 (2021). https://doi.org/10.1007/s00213-021-05870-3
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DOI: https://doi.org/10.1007/s00213-021-05870-3