Opposite roles of dopamine and orexin in quinpirole-induced excessive drinking: a rat model of psychotic polydipsia

Milella, Michele Stanislaw; Passarelli, Francesca; Carolis, Lorenza De; Schepisi, Chiara; Nativio, Paola; Scaccianoce, Sergio; Nencini, Paolo

doi:10.1007/s00213-010-1909-5

Cited by 16 publications

(9 citation statements)

References 60 publications

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“…Second, the systemic administration of the D2/D3 receptors agonist quinpirole, which impairs reversal learning, 50 have also been shown to increase non-regulatory water intake in rats by contra-freeloading, a proposed model of psychotic polydipsia. 70–72 Third, serotonin depletion has been shown to increase behavioral inflexibility. 68,73 Furthermore, a low tryptophan diet has shown to increase compulsive drinking in HD rats on SIP (Merchan et al, unpublished).…”

Section: Discussionmentioning

confidence: 99%

Behavioral Biomarkers of Schizophrenia in High Drinker Rats: A Potential Endophenotype of Compulsive Neuropsychiatric Disorders

Navarro

Álvarez

Colomina

et al. 2016

Schizophrenia Bulletin

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Psychogenic polydipsia, which is compulsive, non-regulatory fluid consumption, is present in 6%–20% of chronic psychiatric patients and frequently associated with the schizophrenia diagnosis. In the present study, we investigated the relation between schizophrenia-like symptoms and biomarkers with a compulsive drinking behavior phenotype in rats. Rats that were selected for low drinking vs high drinking behavior following schedule-induced polydipsia (SIP) were assessed in a latent inhibition (LI) paradigm using tone and electrical foot shock and in a spatial reversal learning task to evaluate behavioral inflexibility. We also analyzed the myelin basic protein in different brain areas of high drinker (HD) and low drinker (LD) rats. The HD rats, which were characterized by a compulsive drinking behavior on SIP, had a reduced level of LI effect and increased behavioral inflexibility in the spatial reversal learning task in comparison to the LD group. Moreover, HD rats showed less myelination in the center of the corpus callosum, striatum, and amygdala in comparison to LD rats. These findings strengthen the validity of HD rats that were selected by SIP as a possible phenotype of compulsive neuropsychiatric disorders, as evidenced by the existence of behaviors and biological markers that are related to schizophrenia and obsessive-compulsive disorder, including a reduced LI effect, behavioral inflexibility and reduced brain myelination. Future studies could contribute to the elucidation of the mechanisms underlying the compulsive phenotype of HD rats and its relation to vulnerability to schizophrenia.

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Section: Discussionmentioning

confidence: 99%

Behavioral Biomarkers of Schizophrenia in High Drinker Rats: A Potential Endophenotype of Compulsive Neuropsychiatric Disorders

Navarro

Álvarez

Colomina

et al. 2016

Schizophrenia Bulletin

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“…Co-administration of the tricyclic antidepressant clomipramine, effective in ameliorating symptoms in the treatment of OCD (Piccinelli et al, 1995), adds to the predictive validity of QNP-sensitization as a rat model of OCD (Szechtman et al, 1998). Additionally, the behavioral effects of chronic QNP administration are considered also to mimic some of behavioral characteristics of schizophrenia, specifically psychotic polydipsia (Goldman et al, 1988; De Carolis et al, 2010, 2011; Milella et al, 2010). …”

Section: Introductionmentioning

confidence: 99%

Spatial Reversal Learning in Chronically Sensitized Rats and in Undrugged Sensitized Rats with Dopamine D2-Like Receptor Agonist Quinpirole

Hatalova

Radostová

Pistikova

et al. 2014

Front. Behav. Neurosci.

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Dopamine plays a role in generating flexible adaptive responses in changing environments. Chronic administration of D2-like agonist quinpirole (QNP) induces behavioral sensitization and stereotypical behaviors reminiscent of obsessive–compulsive disorder (OCD). Some of these symptoms persist even after QNP discontinuation. In QNP-sensitization, perseverative behavior has often been implicated. To test the effect of QNP-sensitization on reversal learning and its association with perseveration we selected an aversively motivated hippocampus-dependent task, active place avoidance on a Carousel. Performance was measured as the number of entrances into a to-be-avoided sector (errors). We tested separately QNP-sensitized rats in QNP-drugged and QNP-undrugged state in acquisition and reversal tasks on the Carousel. In acquisition learning there were no significant differences between groups and their respective controls. In reversal, QNP-sensitized drugged rats showed a robust but transient increase in number of errors compared to controls. QNP-sensitized rats in an undrugged state were not overtly different from the control animals but displayed an altered learning manifested by more errors at the beginning compensated by quicker learning in the second session compared to control animals. Importantly, performance was not associated with perseveration in neither QNP-sensitized drugged nor QNP-sensitized undrugged animals. The present results show that chronic QNP treatment induces robust reversal learning deficit only when the substance is continuously administered, and suggest that QNP animal model of OCD is also feasible model of cognitive alterations in this disorder.

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“…The average consumption for subjects preexposed to vehicle was 15.4896 (+/− 0.5930). Although the basis for these differences is not known, it is possible that indirect DA agonist activity (as a result of DAT inhibition) may have impacted overall drinking either directly or indirectly via compensation (see Amato et al, 2008; De Carolis et al, 2010; Milella et al, 2010 for examples using polydipsia). Interestingly, such increases in consumption during preexposure with other compounds have also been reported (see Serafine & Riley, 2009).…”

Section: Resultsmentioning

confidence: 99%

Dopamine mediates cocaine-induced conditioned taste aversions as demonstrated with cross-drug preexposure to GBR 12909

Serafine

Briscione

Rice

et al. 2012

Pharmacology Biochemistry and Behavior

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Although cocaine readily induces taste aversions, little is known about the mechanisms underlying this effect. It has been suggested that its inhibitory effects at one of the monoamine transporters may be mediating this suppression. Using the cross-drug preexposure preparation, the present series of studies examined a possible role of dopamine (DA) in this effect. Male Sprague-Dawley rats were exposed to cocaine (18 mg/kg; Experiment 1) or the selective DA transporter (DAT) inhibitor GBR 12909 (50 mg/kg; Experiment 2) prior to the pairing of a novel saccharin solution with injections of GBR 12909 (32 mg/kg), cocaine (18 mg/kg) or vehicle in a conditioned taste aversion (CTA) procedure. Preexposure to cocaine attenuated aversions induced by itself but not aversions induced by GBR 12909 (Experiment 1). Conversely, preexposure to GBR 12909 attenuated aversions induced by itself and cocaine (Experiment 2). This asymmetry suggests that cocaine and GBR 12909 induce CTAs via similar, but non-identical, mechanisms. These data are discussed in the context of previous work demonstrating roles for dopamine, norepinephrine and serotonin in cocaine-induced CTAs.

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Opposite roles of dopamine and orexin in quinpirole-induced excessive drinking: a rat model of psychotic polydipsia

Cited by 16 publications

References 60 publications

Behavioral Biomarkers of Schizophrenia in High Drinker Rats: A Potential Endophenotype of Compulsive Neuropsychiatric Disorders

Behavioral Biomarkers of Schizophrenia in High Drinker Rats: A Potential Endophenotype of Compulsive Neuropsychiatric Disorders

Spatial Reversal Learning in Chronically Sensitized Rats and in Undrugged Sensitized Rats with Dopamine D2-Like Receptor Agonist Quinpirole

Dopamine mediates cocaine-induced conditioned taste aversions as demonstrated with cross-drug preexposure to GBR 12909

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