The cannabinergic system is implicated in the upregulation of central NGF protein by psychotropic drugs.
Psychopharmacology (Berl)
; 215(1): 129-41, 2011 May.
Article
em En
| MEDLINE
| ID: mdl-21170518
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 CB(1) 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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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Psicotrópicos
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Encéfalo
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Fator de Crescimento Neural
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Moduladores de Receptores de Canabinoides
Limite:
Animals
Idioma:
En
Ano de publicação:
2011
Tipo de documento:
Article