 |
Ronald P. Hammer, Jr., PhDProfessor, Department of Basic Medical Sciences - The University of Arizona College of Medicine—Phoenix in partnership with Arizona State University Professor, Department Pharmacology - The University of Arizona College of Medicine Professor, Department of Psychology - Arizona State University
UA Office Phone: (602) 827-2112 |
Education:Post-Doc: Neurobiology; UCLA; 1981 PhD; UCLA; 1980
Background:Dr. Hammer obtained a PhD in anatomy and conducted postdoctoral studies in neurobiology at UCLA before becoming a Staff Fellow, then Senior Staff Fellow in the Intramural Research Program at the National Institute of Mental Health in Bethesda, Maryland. In 1984, he became Associate Professor of Anatomy and Pharmacology at the University of Hawaii School of Medicine, where he taught gross anatomy and medical neuroscience, and rose to the rank of Professor in 1993. He received a Research Career Development Award from the National Institute of Neurological Disorders and Stroke in 1987, and was Visiting Associate Research Anatomist at UCLA from 1987-1993. In 1994, he moved to Tufts University School of Medicine, where he was Professor of Psychiatry, Anatomy, Pharmacology and Neuroscience, and Director of the Laboratory of Research in Psychiatry. He served as Course Director for Addiction Medicine and Psychopathology courses, taught Medical Neuroscience and Medical Pharmacology, and served as Associate Dean for Educational Affairs at Tufts University School of Medicine from 1998-1999. He also held an appointment as Lecturer on Psychiatry at Harvard Medical School, and Visiting Scientist in the Alcohol and Drug Abuse Research Center at McLean Hospital from 1994-2006. In 2006, he moved to Phoenix as Professor of Basic Medical Sciences at the University of Arizona College of Medicine. Research Interests:My laboratory studies plasticity and neural adaptation in mesocorticolimbic systems. We have focused on the nucleus accumbens (NAc) due to its involvement in addiction and certain symptoms of schizophrenia (i.e., sensorimotor gating deficits), but we are currently developing strategies for elucidating caudate dysfunction which may afford a more unified model of etiology in schizophrenia. Furthermore, the lack of plasticity and consequent behavioral rigidity which this model attributes to caudate dysfunction are common features of other neuropsychiatric disorders, such as autism, obsessive-compulsive disorder and Tourette syndrome. This work is interdisciplinary, involving cellular and molecular neurobiology and neuropsychopharmacology, and translational by nature, permitting the extension of our basic research findings into potential therapies for neuropsychiatric disorders.
Molecular and genetic substrates of neuropsychiatric disorders Sensorimotor gating deficits also serve as an endophenotype amenable to genetic analysis. We utilized prepulse inhibition to determine putative sensorimotor gating genes in consomic (chromosome substitution) mouse strains in collaboration with colleagues at the MIT/Harvard Broad Institute. Thus far, we have identified chromosome 16 as a putative locus, along with two genes that are differentially expressed and map to a suggestive sensorimotor gating QTL in consomic mice. One of these is the D3 receptor gene, supporting our hypothesis that D3 receptor-related neuroadaptation regulates recovery of sensorimotor gating. The intracellular adaptation associated with recovery of sensorimotor gating, enhanced CREB activation, is clinically significant because it is identical to that observed upon treatment with existing antipsychotic drugs. Furthermore, the selectivity of this effect in NAc reduces the possibility of extrapyramidal side effects. Although experimental inactivation of Gi/Go proteins in the NAc is capable of attenuating dopamine-induced sensorimotor gating deficits, we showed that coupling of D2-like receptors to G proteins is not altered by the low doses of agonist drugs that produce behavioral recovery. Thus, receptor function remains intact even after chronic treatment. Together, these data reveal that compensatory neuroadaptation in NAc neurons has antipsychotic-like effects which may lead to a palliative “cure” for these schizophrenia symptoms. Future studies will utilize a different behavioral model, conditioned avoidance responding, to confirm the antipsychotic efficacy of this approach.
Neuronal and neurochemical effects of stress and psychostimulant drugs Recent work explores the role of corticosterone and corticotropin releasing factor (CRF) in stress-induced brain changes. Our results reveal that corticosterone is not directly involved; rather, elevated CRF disrupts sensorimotor gating. This effect is blocked by clozapine and attenuated by the selective D2-like receptor antagonist, raclopride, implicating dopamine in the mechanism of CRF-induced sensorimotor gating disruption. Furthermore, pretreatment with raclopride alters CRF-induced Fos expression in the NAc and amygdala, suggesting that these regions mediate CRF-induced sensorimotor gating deficits. Exposure to social defeat stress also causes behavioral cross-sensitization to psychostimulants. We have shown that repeated cocaine self-administration that induces behavioral sensitization selectively increases functional activation of limbic frontal cortical neurons that innervate the NAc in response to drug challenge, even in the absence of altered expression of glutamate receptor subunits in the NAc. We showed that chronic social stress exposure induces transient expression of functional µ-opioid receptors in ventral tegmental area which increases mesolimbic dopamine tone. However, a subsequent induction of brain-derived neurotrophic factor may underlie the eventual transition to long-lasting drug cross-sensitization. Thus, mesocorticolimbic output can convey motivation and control behavior by regulating various neural circuits utilizing different signaling mechanisms.
A cognitive neuroscience approach to schizophrenia We are developing a testable model of caudate involvement in positive symptoms of schizophrenia. The basis of this model is that limbic, motor and cognitive striatum are connected via parallel circuits which originate and terminate in various cortical regions. Just as putamen regulates the initiation of motor activity and the generation of motor patterns, we propose that caudate regulates the initiation of cognitive activity (i.e., thoughts) and generation of cognitive patterns (i.e., beliefs). Thus, dysfunction caused by excessive dopamine in caudate may lead to abnormal thoughts or beliefs related to specific cortical regions, thereby producing hallucinations or delusions, the hallmarks of psychosis. Furthermore, reduced glutamatergic stimulation of caudate would enhance this effect, and deficient glutamate-associated plasticity would promote behavioral rigidity and "fixed" cognitive patterns observed in schizophrenia. Ongoing experiments assess cortical response to intracranial manipulation of relevant receptors in rat caudate to demonstrate the putative substrate of these effects. Search PubMed for a complete listing of Dr. Hammer's publications PubMed Link:Search PubMed for a complete listing of Dr. Hammer's publications Selected Publications:
|
|
All contents ©2007 Arizona Board of Regents. All rights reserved. The University of Arizona is an EEO/AA - M/W/D/V Employer.