title: The cannabinergic system is implicated in the upregulation of central NGF protein by psychotropic drugs.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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.
authors.affiliation: Research Center for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Pari_has@yahoo.com
authors.forename: Parichehr
authors.initials: P
authors.lastname: Hassanzadeh
authors.forename: Sina
authors.initials: S
authors.lastname: Rahimpour
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D063385:Cannabinoid Receptor Modulators / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D008297:Male; D020932:Nerve Growth Factor / Q000096:biosynthesis*; D011619:Psychotropic Drugs / Q000009:adverse effects* / Q000737:chemistry; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D043884:Receptor, Cannabinoid, CB1 / Q000037:antagonists & inhibitors; D013329:Structure-Activity Relationship; D013997:Time Factors; D015854:Up-Regulation
chemical_list: C529765:AM4113; D063385:Cannabinoid Receptor Modulators; D011619:Psychotropic Drugs; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; D020932:Nerve Growth Factor