Osvaldo Giorgi

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RESEARCH OVERVIEWOsvaldo Giorgi received his M.D. degree from the University of Buenos Aires and, in 2002, he was appointed to his current position as Full Professor of Pharmacology at the School of Pharmacy of the University of Cagliari. His approach to Neuroscience research is based on a combination of biochemical methods (HPLC and brain microdialysis, radioligand binding, enzyme assays, and analysis of gene expression) with animal models of psychiatric disorders. He has co-authored over 85 articles (I.F.: 28, SCOPUS, 2875 citations) published in international journals mostly related to studies on the effects of anxiolytic, antidepressant and antipsychotic agents, as well as drugs of abuse, on GABAergic, dopaminergic and serotoninergic neurotransmission. In view of the important role played by genetic factors in the pathogenesis of the most prevalent psychiatric diseases, in recent years he has focused his interest on behavioral and neurochemical studies in psychogenetically selected animals, the Roman high-avoidance and Roman low-avoidance rats. These studies (which receive financial support from public and private agencies) are aimed at characterizing the role of the genetic make up in the neurobiological mechanisms involved in anxiety, depression, and addiction.

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C-Fos, BDNF and TRKB Expression After Neonatal Handling in Social Brain Regions: Distinctive Profile of Rha-Rat Schizophrenia Model on a Social Preference Test

IBRO Neuroscience Reports

Lip 20583

Role of dopamine in alcohol addiction

5-HT< sub> 1A</sub> receptor mRNA expressions differ in the embryonic spinal cord of male and female rats

Neuroscience …, 1997

During critical periods of development, the effects of testosterone (T) on promoting androgenizat... more

Characterization of the biochemical parameters of GABAergic and Dopaminergic neurotransmission in the cerebral cortex of Roman high-avoidance and Roman low-avoidance rats

I ratti delle linee Roman (High e Low Avoidance) presentano differenze nel comportamento sessuale: ruolo del sistema dopaminergico mesolimbico

Outbred male Roman high and low avoidance rats show different patterns of copulatory behaviour: comparison with Sprague Dawley rats

Chronic cocaine induces behavioral sensitization and opposite changes in core and shell accumbal dopamine output in Roman high- (RHA) but not in Roman low-avoidance (RLA) rats

c-Fos expression after neonatal handling in social brain regions: distinctive profile of RHA-rat schizophrenia model on a social preference test

Behavioural Brain Research, Aug 1, 2023

Attività del sistema dopaminergico mesocorticale durante il comportamento sessuale: ruolo dell’esperienza e delle differenze individuali

Repeated morphine injections induce behavioral sensitization in Roman High-, but not in Roman Low-Avoidance rats

The Society for Neuroscience Abstracts, Sep 20, 2000

Increased responsiveness to cocaine and amphetamine in rats with neonatal excitotoxic damage of the ventral hippocampus

Voluntary ethanol intake activates meso-accumbal dopaminergic transmission in Roman high-avoidance, but not Roman low-avoidance rats

Journal of Neurochemistry, 2001

Dissociation between cortical dopamine and serotonin output and fear-like behaviors in two lines of rats that display different coping strategies in response to stress

A comparative study of the biochemical parameters of the GABAergic and dopaminergic neurotransmission in the brain of Roman high-avoidance and Roman low-avoidance rats

Neurobehavioral and neurodevelopmental profiles of a heuristic genetic model of differential schizophrenia- and addiction-relevant features: The RHA vs. RLA rats

Neuroscience & Biobehavioral Reviews, 2021

The Roman High- (RHA) and Low-(RLA) avoidance rat lines/strains were generated through bidirectio... more The Roman High- (RHA) and Low-(RLA) avoidance rat lines/strains were generated through bidirectional selective breeding for rapid (RHA) vs. extremely poor (RLA) two-way active avoidance acquisition. Compared with RLAs and other rat strains/stocks, RHAs are characterized by increased impulsivity, deficits in social behavior, novelty-induced hyper-locomotion, impaired attentional/cognitive abilities, vulnerability to psychostimulant sensitization and drug addiction. RHA rats also exhibit decreased function of the prefrontal cortex (PFC) and hippocampus, increased functional activity of the mesolimbic dopamine system and a dramatic deficit of central metabotropic glutamate-2 (mGlu2) receptors (due to a stop codon mutation at cysteine 407 in Grm2 -cys407*-), along with increased density of 5-HT2A receptors in the PFC, alterations of several synaptic markers and increased density of pyramidal "thin" (immature) dendrític spines in the PFC. These characteristics suggest an immature brain of RHA rats, and are reminiscent of schizophrenia features like hypofrontality and disruption of the excitation/inhibition cortical balance. RHA rats represent a promising heuristic model of neurodevelopmental schizophrenia-relevant features and comorbidity with drug addiction vulnerability.

Decreased social interaction in the RHA rat model of schizophrenia-relevant features: Modulation by neonatal handling

Behavioural Processes, 2021

The Roman-Low (RLA) and High-Avoidance (RHA) rat strains have been bidirectionally selected and b... more The Roman-Low (RLA) and High-Avoidance (RHA) rat strains have been bidirectionally selected and bred, respectively, for extremely poor vs. rapid acquisition of the two-way active avoidance task. Over 50 years of selective breeding have led to two strains displaying many differential specific phenotypes. While RLAs display anxious-related behaviours, RHA rats show impulsivity, and schizophrenia-like positive and cognitive symptoms or phenotypes. Neonatal handling (NH) is an environmental treatment with long-lasting anxiolytic-like and anti-stress effects. NH also reduces symptoms related to schizophrenia, such as pre-pulse inhibition (PPI) impairment and latent inhibition (LI) deficits, and improves spatial working memory and cognitive flexibility. The present work was aimed at exploring whether RHAs also display negative schizophrenia-like symptoms (or phenotypes), such as lowered preference for social interaction (i.e. asociality), and whether NH would reduce these deficits. To this aim, we evaluated naïve inbred RHA and RLA rats in a social interaction (SI) test after either long- or short-term habituation to the testing set up (studies 1-2). In Study 3 we tested untreated and NH-treated RHA and RLA rats in novel object exploration (NOE) and SI tests. Compared with RHAs, RLA rats displayed increased anxiety-related behaviours in the NOE (i.e. higher behavioural inhibition, lesser exploration of the novel object) and SI (i.e. higher levels of self-grooming) tests which were dramatically reduced by NH treatment, thus supporting the long-lasting anxiolytic-like effect of NH. Remarkably, RHA rats showed decreased social preference in the SI test compared with RLAs, evidencing that RHAs would present a relative asociality, which is thought to model some negative symptomatology (i.e. social withdrawal) of schizophrenia. NH increased absolute levels of social behaviour in both strains, but with a more marked effect in RHA rats, especially in the first 5 minutes of the SI test. Thus, it is hypothesized that, apart from its effects on anxiety-related behaviours, NH might have long-lasting positive effects on behavioural and neurobiological processes that are impaired in schizophrenia.

Active avoidance learning differentially activates ERK phosphorylation in the primary auditory and visual cortices of Roman high- and low-avoidance rats

Physiology & Behavior, 2018

Understanding the mechanisms underlying conditioned avoidance is a critical step toward the devel... more Understanding the mechanisms underlying conditioned avoidance is a critical step toward the development of novel treatments of anxiety. In this context, the two-way active avoidance (2WAA) task is a validated paradigm to investigate uncontrolled avoidance, a hallmark of anxiety disorders. The outbred Roman high-(RHA) and lowavoidance (RLA) rat lines are selected for respectively rapid vs. poor acquisition of active avoidant behavior, and emotional reactivity appears to be the most prominent behavioral difference between the two lines, with RLA rats being more fearful/anxious than their RHA counterparts. This study was aimed at assessing the relationship between the different performance of RHA and RLA rats in the 2WAA task and the number of phosphorylated ERK positive (pERK+) neurons in the primary auditory and visual cortices, in three sub-nuclei of the amygdala, as well as in the nucleus accumbens, and the prefrontal cortex. The results indicate that: (1) RHA rats, but not their RLA counterparts, learn very rapidly to avoid mild electric foot-shocks by crossing to the opposite compartment of the shuttle-box during the presentation of the conditioned stimulus and (2) the different behavior of the Roman lines during active avoidance training is associated with differential changes in the number of pERK + neurons in the primary auditory and visual cortices (where the proactive coping of RHA rats is associated with increased ERK phosphorylation), but not in the other brain areas examined. These results are consistent with the hypothesis that the activation of the ERK signaling cascade in the auditory and visual cortices may be involved in the acquisition of aversive learning in RHA rats.

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MK-801 Prevents Chemical Dindling Induced by Pentylenetetrazol in Rats

European Journal of Pharmacology, 1991

Decrease in the function of the g-aminobutyric acid-coupled chloride channel produced by the repeated administration of pentylenetetrazole to rats

Osvaldo Giorgi

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