University of Louis Pasteur
Strasbourg, Alsace, France
| schizophrenia|| endocannabinoid system|
| sub-chronic PCP rat model|| neuropsychopharmacology|
| behavioral neurosciences|
Schizophrenia is a severe mental illness characterized by three main types of symptoms: positive (e.g. hallucinations, delusions), negative (e.g. social withdrawal, anhedonia), and cognitive deficits (e.g. impaired working memory and attention). Whereas hallucinations and delusions are the most vivid and conspicuous symptoms of schizophrenia, the other sets of symptoms are much more pervasive and persistent. Recent studies point to the negative symptoms of schizophrenia as the illness core and, together with the cognitive deficits, as the most significant factor contributing to the functional impairments associated with the disease. In addition, positive symptoms can often be effectively treated with antipsychotic drugs, whereas the pharmacotherapy of the negative symptoms has been generally disappointing. Thus, there is clear need to better understand the pathophysiology of negative symptoms, identify novel pharmacological targets and translate this knowledge into new therapies.
Alterations in several neurotransmitter systems and neuroanatomical changes have been reported in the brain of schizophrenic patients. The ‘cannabinoid hypothesis’ of schizophrenia, which was originally based on the observation that the psychotomimetic ingredient of marijuana, delta-9-tetrahydrocannabinol, can exacerbate psychosis, postulates that over-activity of the brain endocannabinoid system might contribute to the hyper-dopaminergic and hypo-glutamatergic transmission underlying the positive and negative symptoms of schizophrenia. However, recent advances in the neurobiology of the endocannabinoid system have revisited the association between cannabinoids and schizophrenia, particularly in the context of understanding the neural basis of negative symptoms. Our goal is to clarify the role played by this system in schizophrenia, with special emphasis on the negative symptomatology of this disease.
Given the fact that chronic phencyclidine (PCP) abusers have been commonly misdiagnosed as schizophrenic, and the unparalleled ability of PCP to model the complex facets of schizophrenia (clinically and pathologically), we are using the sub-chronic PCP rat model to reproduce behavioral deficits that closely resemble schizophrenic symptoms, and in particular the negative ones. Using this behavioral approach, in conjunction with the use of innovative pharmacological tools, and complemented by the measurements of endocannabinoids (by mass spectrometry) and related molecular targets in the brain, we have shown that PCP-induced social withdrawal arises from deficient stimulation of cannabinoid CB1 receptors.
Accomplishments, Awards and Honors
UTHSCSA 11th Annual Center for Biomedical Neuroscience (CBN) Retreat - 1st Place - Outstanding Junior Faculty Poster Presentation - San Antonio, TX (2013)
UTHSCSA Pharmacology 17th Annual Graduate Student Symposium - 1st Place - Postdoctoral Poster - San Antonio, TX (2010)
UTHSCSA 17th Annual Terry Mikiten Graduate Student Association Research Forum - 1st Place - Postdoctoral Poster - San Antonio, TX (2010)
Society for Neuroscience 39th Annual Meeting - SfN Chapters Postdoctoral Trainee Travel Award - Chicago, IL (2009)
UTHSCSA Pharmacology 15th Annual Graduate Student Symposium - 1st Place - Postdoctoral Poster - New Braunfels, TX (2008)
Society for Neuroscience 37th Annual Meeting - SfN Chapters Postdoctoral Trainee Travel Award - San Diego, CA (2007)
Graduate Student Association Research Forum - 1st Place - Postdoctoral Poster - San Antonio, TX (2007)
Lectures and Presentations
'Social Withdrawal in schizophrenia: from cannabis to endocannabinoids' - UTHSCSA Pharmacology Seminar Series - San Antonio, TX (March 2011)
'Endocannabinoid tone in a rat model of schizophrenia: the good, the bad and the ugly' - UTHSCSA Addiction Seminar - San Antonio, TX (December 2010)