My laboratory is interested in understanding the neural substrates of substance use disorder comorbidity in schizophrenia. It has been posited that underlying patterns of corticolimbic abnormalities responsible for schizophrenia affect the function of primary motivational circuitry, such that the reinforcing effects of addictive drugs and their capacity to produce substance use disorders are increased. To test this hypothesis, we are using neonatal ventral hippocampal lesions (NVHLs) as a neurodevelopmental rat model of schizophrenia. Our studies use neurochemical methods (brain microdialysis and analysis of gene expression) combined with behavioral paradigms in experiments aimed at characterizing, in rats sustaining NVHLs, the alterations in the neural systems that mediate reward and craving (in particular, dopaminergic transmission in the mesoaccumbens projection) that result from the drug addiction process. Our results show that NVHLs induce alterations in the responses to acute psychostimulants of accumbal dopaminergic terminals and provide a link among the hippocampal damage, the hyperactivity in mesolimbic dopamine transmission, and the increased vulnerability to drug abuse comorbidity observed in schizophrenics. A related interest is to understand the role of the neural circuits that mediate reward in the regulation of normal mood as well as the abnormalities in mood and motivation seen in depression. In this project, we are using an animal model of genetically determined vulnerability to stress and depression, the Roman low-avoidance (RLA) rats, which are selectively bred for extremely poor acquisition of avoidant behavior in the shuttle-box. The results of the research will guide future efforts toward the design of novel therapies for schizophrenia, addiction, and depression.

Maria G. Corda, PhD is an Associate Professor of Pharmacology at the University of Cagliari School of Pharmacy. Dr. Corda received her PhD degree in Biology at the University of Cagliari and completed her training in biochemistry and psychopharmacology as a Fogarty Fellow at the Laboratory of Preclinical Pharmacology, NIMH, NIH (Washington, DC).

O. Giorgi, G. Piras, D. Lecca, S. Hansson, P. Driscoll, M.G. Corda. Differential neurochemical properties of central serotonergic transmission in Roman high- and low-avoidance rats. J Neurochem. 86: 422-431, 2003.
O. Giorgi, D. Lecca, G. Piras, P. Driscoll, M.G. Corda. Dissociation between mesocortical dopamine release and fear-related behaviours in two psychogenetically selected lines of rats that differ in coping strategies to aversive conditions. Eur. J. Neurosci. 17: 2716-2726, 2003.
G. Piras, D. Lecca, M.G. Corda, O. Giorgi. Repeated morphine injections induce behavioural sensitization in Roman high-, but not in Roman low-avoidance rats. Neuroreport 14: 2483-2488, 2003.
D. Lecca, G. Piras, P. Driscoll, O. Giorgi, M.G. Corda. A differential activation of dopamine output in the shell and core of the nucleus accumbens is associated with the motor responses to addictive drugs: A brain dialysis study in Roman high- and low-avoidance rats. Neuropharmacology 46: 688-699, 2004.
O. Giorgi, G. Piras, D. Lecca, M.G. Corda. Behavioural effects of acute and repeated cocaine treatments: A comparative study in sensitisation-prone RHA rats and their sensitisation-resistant RLA counterparts. Psychopharmacology, 180: 530-538, 2005.
M.G. Corda, G. Piras, D. Lecca, A. Fernández-Teruel, P. Driscoll, O. Giorgi. The psychogenetically selected Roman rat lines differ in the susceptibility to develop amphetamine sensitization. Behav. Brain Res. 157: 147-156, 2005.
O. Giorgi, D. Lecca G. Piras, M.G. Corda. Differential activation of dopamine release in the nucleus accumbens core and shell after acute or repeated amphetamine injections: A comparative study in the Roman high- and low-avoidance rat lines. Neuroscience, 135: 987-998, 2005.
M.G. Corda, G. Piras, O. Giorgi. Neonatal ventral hippocampal lesions potentiate amphetamine-induced increments in dopamine efflux in the core, but not shell, of the nucleus accumbens. Biol. Psychiatry 60: 1188-1195, 2006.
O. Giorgi, G. Piras, M.G. Corda. The psychogenetically selected Roman high- and low-avoidance rat lines: A model to study the individual vulnerability to drug addiction. Neurosci Biobehav Rev., 31: 148-163, 2007.