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The cannabinergic system is implicated in the upregulation of central NGF protein by psychotropic drugs

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Abstract

Rationale

Studies on the regulation of nerve growth factor (NGF) levels by psychotropics are limited in scope and the mechanism(s) remain elusive which merit further elucidation.

Objectives

We aimed to perform a more comprehensive investigation on the possible effects of pharmacologically heterogeneous groups of psychotropic drugs on NGF contents in the brain regions involved in the modulation of emotions. As a mechanistic approach, we looked at the role of the cannabinergic system which is linked to depression and/or antidepressant effect and appears to interact with neurotrophin signaling.

Methods

Following psychotropic treatment, NGF or endocannabinoid (eCB) contents were quantified by Bio-Rad protein assay and isotope-dilution liquid chromatography/mass spectrometry, respectively. In case of any significant change, the effects of pretreatment with the CB1 receptor neutral antagonist AM4113 were investigated.

Results

Single injection of nortriptyline, isocarboxazid, citalopram, diazepam, risperidone (2.5, 5, and 10 mg/kg, each), and fluphenazine (0.25, 0.5, and 1 mg/kg) into rats did not alter NGF or eCB contents. Following 4-week treatment, all drugs except diazepam elevated NGF or eCB levels in dose-dependent and brain region-specific fashion. Pretreatment with the highest dose of AM4113 (5.6 mg/kg) prevented psychotropic-induced NGF or eCB elevation. AM4113 had no effect by itself.

Conclusions

The cannabinergic system is implicated in the mechanisms of action of certain psychotropic drugs including the upregulation of brain NGF levels. This provides a better understanding of the pathophysiological mechanisms underlying neuropsychiatric disorders, leading to novel drug design.

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Acknowledgments

The experiments comply with the current laws of Iran. This work was funded in part by a grant (A-1142) from AJA University of Medical Sciences. The authors thank Dr. Ali Mahdavi, Department of Immunology, Tarbiat Modarres University, Tehran; Amir Farahbakhsh, Department of Molecular Biology, Azad University, Parand; and Fatemeh Eini, AJA University of Medical Sciences, for their technical assistance. The authors greatly thank Professors Richard A. Lockshin (St. John’s University, USA), George Chaldakov (Medical University of Varna, Bulgaria), Andrew Greenshaw (University of Alberta, Canada), and Luigi Aloe (Institute of Neurobiology and Molecular Medicine, Rome, Italy) for their helpful comments and encouragement.

Disclosure/Conflicts of interest

The authors declare that, except for the income received from AJA University of Medical Sciences, no financial support or compensation has been received from any individual or corporate entity. There are no personal financial holdings that could be perceived as consulting a potential conflict of interest.

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Authors and Affiliations

  1. Research Center for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, P.O. Box 19835-187, Evin, Tehran, Iran

    Parichehr Hassanzadeh

  2. Neuropsychopharmacology Research Center, AJA University of Medical Sciences, Tehran, Iran

    Parichehr Hassanzadeh

  3. Department of Pharmacology, Tehran University of Medical Sciences, Tehran, Iran

    Sina Rahimpour

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  1. Parichehr Hassanzadeh
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  2. Sina Rahimpour
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Correspondence to Parichehr Hassanzadeh.

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Hassanzadeh, P., Rahimpour, S. The cannabinergic system is implicated in the upregulation of central NGF protein by psychotropic drugs. Psychopharmacology 215, 129–141 (2011). https://doi.org/10.1007/s00213-010-2120-4

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  • DOI: https://doi.org/10.1007/s00213-010-2120-4

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