title: Increasing endocannabinoid levels in the ventral pallidum restore aberrant dopamine neuron activity in the subchronic PCP rodent model of schizophrenia.
abstract: BACKGROUND
  Schizophrenia is a debilitating disorder that affects 1% of the US population. While the exogenous administration of cannabinoids such as tetrahydrocannabinol is reported to exacerbate psychosis in schizophrenia patients, augmenting the levels of endogenous cannabinoids has gained attention as a possible alternative therapy to schizophrenia due to clinical and preclinical observations. Thus, patients with schizophrenia demonstrate an inverse relationship between psychotic symptoms and levels of the endocannabinoid anandamide. In addition, increasing endocannabinoid levels (by blockade of enzymatic degradation) has been reported to attenuate social withdrawal in a preclinical model of schizophrenia. Here we examine the effects of increasing endogenous cannabinoids on dopamine neuron activity in the sub-chronic phencyclidine (PCP) model. Aberrant dopamine system function is thought to underlie the positive symptoms of schizophrenia.
  
  
  METHODS
  Using in vivo extracellular recordings in chloral hydrate-anesthetized rats, we now demonstrate an increase in dopamine neuron population activity in PCP-treated rats.
  
  
  RESULTS
  Interestingly, endocannabinoid upregulation, induced by URB-597, was able to normalize this aberrant dopamine neuron activity. Furthermore, we provide evidence that the ventral pallidum is the site where URB-597 acts to restore ventral tegmental area activity.
  
  
  CONCLUSIONS
  Taken together, we provide preclinical evidence that augmenting endogenous cannabinoids may be an effective therapy for schizophrenia, acting in part to restore ventral pallidal activity.
authors.affiliation: Department of Pharmacology and Center for Biomedical Neuroscience, University of Texas Health Science Center, San Antonio, Texas (Aguilar, Drs Chen and Lodge); Departments of Physiology & Pathophysiology, Medical School of Xi'an Jiaotong University, Xi'an, Shaanxi, China (Dr Chen). aguilardd@livemail.uthscsa.edu.
authors.forename: David D
authors.initials: DD
authors.lastname: Aguilar
authors.affiliation: Department of Pharmacology and Center for Biomedical Neuroscience, University of Texas Health Science Center, San Antonio, Texas (Aguilar, Drs Chen and Lodge); Departments of Physiology & Pathophysiology, Medical School of Xi'an Jiaotong University, Xi'an, Shaanxi, China (Dr Chen).
authors.forename: Li
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Pharmacology and Center for Biomedical Neuroscience, University of Texas Health Science Center, San Antonio, Texas (Aguilar, Drs Chen and Lodge); Departments of Physiology & Pathophysiology, Medical School of Xi'an Jiaotong University, Xi'an, Shaanxi, China (Dr Chen).
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Lodge
mesh_terms: D000818:Animals; D066187:Basal Forebrain / Q000187:drug effects / Q000503:physiopathology*; D001549:Benzamides / Q000494:pharmacology; D002219:Carbamates / Q000494:pharmacology; D002491:Central Nervous System Agents / Q000494:pharmacology; D004195:Disease Models, Animal; D059290:Dopaminergic Neurons / Q000187:drug effects / Q000502:physiology*; D063388:Endocannabinoids / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects / Q000503:physiopathology; D008297:Male; D008839:Microelectrodes; D010622:Phencyclidine; D017207:Rats, Sprague-Dawley; D012559:Schizophrenia / Q000503:physiopathology*; D026941:Sodium Channel Blockers / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology; D017557:Ventral Tegmental Area / Q000187:drug effects / Q000503:physiopathology
chemical_list: D001549:Benzamides; D002219:Carbamates; D002491:Central Nervous System Agents; D063388:Endocannabinoids; D026941:Sodium Channel Blockers; C500528:cyclohexyl carbamic acid 3'-carbamoylbiphenyl-3-yl ester; D013779:Tetrodotoxin; D010622:Phencyclidine
keywords: cannabinoids; hippocampus; phencyclidine; schizophrenia; ventral pallidum