Cannabis intoxication is known to produce psychotic symptoms such as delusions, and disorganized thoughts resembling schizophrenia. In addition, epidemiological data supports a correlation between cannabis use and subsequent development and/or exacerbation of schizophrenia in humans. Schizophrenia is known to inhibit the activity of prefrontal-thalamic-cerebellar network in humans, and has led to the cognitive dysmetria hypothesis of schizophrenia. This posits that a primary dysfunction in the prefrontal-thalamic-cerebellar network underlies the broad range of schizophrenic symptomatology. We will utilize functional magnetic resonance imaging, Fos immunohistochemistry and mass spectroscopy to explore the biological mechanisms by which cannabinoids may inhibit prefrontal-thalamic-cerebellar networks in animals with the aim of further understanding the biological basis for the high correlation between cannabis use and schizophrenia. In addition, we plan to evaluate the role of the endogenous cannabinergic system in the regulation of the prefrontal-thalamic-cerebellar network. We hope that successful completion of these studies will provide enhanced understanding of both the endocannabinoid system and its possible contribution to the pathophysiology of schizophrenia.

National Institute of Health (NIH)
National Institute on Drug Abuse (NIDA)
Individual Predoctoral NRSA for M.D./Ph.D. Fellowships (ADAMHA) (F30)
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Human Development Research Subcommittee (NIDA)
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Lawrence, Diane M
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Medical College of Wisconsin
Schools of Medicine
United States
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Patel, Sachin; Hillard, Cecilia J (2008) Adaptations in endocannabinoid signaling in response to repeated homotypic stress: a novel mechanism for stress habituation. Eur J Neurosci 27:2821-9
Patel, Sachin; Hillard, Cecilia J (2006) Pharmacological evaluation of cannabinoid receptor ligands in a mouse model of anxiety: further evidence for an anxiolytic role for endogenous cannabinoid signaling. J Pharmacol Exp Ther 318:304-11
Rademacher, David J; Patel, Sachin; Ho, W-S Vanessa et al. (2005) U-46619 but not serotonin increases endocannabinoid content in middle cerebral artery: evidence for functional relevance. Am J Physiol Heart Circ Physiol 288:H2694-701
Patel, Sachin; Cravatt, Benjamin F; Hillard, Cecilia J (2005) Synergistic interactions between cannabinoids and environmental stress in the activation of the central amygdala. Neuropsychopharmacology 30:497-507
Hill, Matthew N; Patel, Sachin; Carrier, Erica J et al. (2005) Downregulation of endocannabinoid signaling in the hippocampus following chronic unpredictable stress. Neuropsychopharmacology 30:508-15
Patel, Sachin; Carrier, Erica J; Ho, W-S Vanessa et al. (2005) The postmortal accumulation of brain N-arachidonylethanolamine (anandamide) is dependent upon fatty acid amide hydrolase activity. J Lipid Res 46:342-9
Seagard, Jeanne L; Dean, Caron; Patel, Sachin et al. (2004) Anandamide content and interaction of endocannabinoid/GABA modulatory effects in the NTS on baroreflex-evoked sympathoinhibition. Am J Physiol Heart Circ Physiol 286:H992-1000
Lu, Hanbing; Patel, Sachin; Luo, Feng et al. (2004) Spatial correlations of laminar BOLD and CBV responses to rat whisker stimulation with neuronal activity localized by Fos expression. Magn Reson Med 52:1060-8
Rademacher, David J; Kearn, Christopher S; Carrier, Erica J et al. (2004) Production of hydroxyeicosatetraenoic acids and prostaglandins by a novel rat microglial cell line. J Neuroimmunol 149:130-41
Patel, Sachin; Roelke, Craig T; Rademacher, David J et al. (2004) Endocannabinoid signaling negatively modulates stress-induced activation of the hypothalamic-pituitary-adrenal axis. Endocrinology 145:5431-8

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