Effects of pregabalin on behavioral alterations induced by ketamine in rats

Nunes, Emerson Arcoverde; Canever, Leila; Oliveira, Larissa Bertacchini de; Luca, Renata de; Quevedo, Joao L De; Zugno, Alexandra I.; Peregrino, Antônio Augusto de Freitas; Crippa, José Alexandre S; Dursun, Serdar; Baker, Glen B.; Hallak, Jaime Eduardo Cecílio

doi:10.1016/j.rbp.2012.02.005

Cited by 8 publications

(4 citation statements)

References 14 publications

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“…Pregabalin is used to treat seizures (Panebianco et al, 2019), neuropathic pain (Attal et al, 2010), and anxiety (Slee et al, 2019). Our findings are the first to show that pregabalin can attenuate methamphetamine-induced behavior and compliment studies showing pregabalin-induced decrease in ketamine-(Nunes et al, 2012) and morphine-induced locomotion (Vashchinkina et al, 2018) and in cocaine oral self-administration (de Guglielmo et al, 2013). Prior work with gabapentin, a CACNA2D1 inhibitor, showed a reduction in methamphetamine-induced locomotor sensitization (Kurokawa et al, 2010).…”

Section: Discussionsupporting

confidence: 85%

Cacna2d2 is an hnRNP H target of the striatal mRNA targetome and regulates methamphetamine behavior

Ruan

Rieger²,

Lynch

et al. 2021

Preprint

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We previously identified Hnrnph1 (heterogeneous nuclear ribonucleoprotein H1) as a quantitative trait gene underlying reduced methamphetamine behavioral sensitivity. Mice with a heterozygous frameshift deletion in the first coding exon of Hnrnph1 showed reduced methamphetamine-induced dopamine release and behaviors. To inform the mechanism linking hnRNP H dysfunction with reduced methamphetamine-induced dopamine release and behavior, we surveyed the RNA targetome of hnRNP H via cross-linking immunoprecipitation coupled with RNA-sequencing in striatal tissue at baseline and at 30 min post-methamphetamine (2 mg/kg, i.p.). Methamphetamine induced opposite changes in RNA-binding targets of hnRNP H in Hnrnph1 mutants versus wild-types, including 3′UTR targets in mRNAs enriched for synaptic proteins involved in dopamine release and excitatory synaptic plasticity. Targetome, transcriptome, and spliceome analyses triangulated on a methamphetamine-induced upregulation of Cacna2d2 transcript and decreased 3′UTR usage in hyposensitive Hnrnph1 mutants. Our study identifies a dynamic methamphetamine-induced RNA targetome of hnRNP H that has the potential to rapidly regulate gene expression, synaptic transmission, plasticity, and behavior.

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Section: Discussionsupporting

confidence: 85%

Cacna2d2 is an hnRNP H target of the striatal mRNA targetome and regulates methamphetamine behavior

Ruan

Rieger²,

Lynch

et al. 2021

Preprint

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“…Stereotypy is characterized as repetitive behavior and has been noted in patients with psychosis and also in several pharmacological human and animal models of psychosis [13–18]. Specific behaviors can vary depending on the drug or animal used and behaviors include, but are not limited to, repetitive licking, chewing, grooming, head movements, sniffing, circling, or climbing [17, 19–22].…”

Section: Measurementsmentioning

confidence: 99%

“…Specific behaviors can vary depending on the drug or animal used and behaviors include, but are not limited to, repetitive licking, chewing, grooming, head movements, sniffing, circling, or climbing [17, 19–22]. The level of stereotypy can be determined through either recorded observation or the use of software programmed with predetermined criteria [17, 18, 22]. Stereotypy thus has been used as both a qualitative and quantitative measure in models of psychosis.…”

Section: Measurementsmentioning

confidence: 99%

Animal Models of Psychosis: Current State and Future Directions

Forrest

Coto

Siegel

2014

Curr Behav Neurosci Rep

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Psychosis is an abnormal mental state characterized by disorganization, delusions and hallucinations. Animal models have become an increasingly important research tool in the effort to understand both the underlying pathophysiology and treatment of psychosis. There are multiple animal models for psychosis, with each formed by the coupling of a manipulation and a measurement. In this manuscript we do not address the diseases of which psychosis is a prominent comorbidity. Instead, we summarize the current state of affairs and future directions for animal models of psychosis. To accomplish this, our manuscript will first discuss relevant behavioral and electrophysiological measurements. We then provide an overview of the different manipulations that are combined with these measurements to produce animal models. The strengths and limitations of each model will be addressed in order to evaluate its cross-species comparability.

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“…Pregabalin has been tested in animal models where it was able to counteract behavioral alterations induced by ketamine in rats and modulate sensorimotor gating [105,106]. Pregabalin was successfully used for the management of treatment-resistant anxious syndromes in schizophrenia [107][108][109] and should be further evaluated, in particular because of incompletely understood pharmacokinetic interactions [110].…”

Section: Mk-801 Olz and Other Fgas And Sgasmentioning

confidence: 99%

Glutamatergic agents for schizophrenia: current evidence and perspectives

Zink

Correll

2015

Expert Review of Clinical Pharmacology

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Suboptimal outcomes in schizophrenia are a consequence of lacking insight into the etiology, biomarkers and treatment-relevant subgroups, the therapeutic restriction to dopaminergic-modulating antipsychotics that fail to significantly improve negative and cognitive symptoms, non-adherence, and, in the case of treatment-resistance, the underutilization of clozapine. Evidence suggests additional, extra-dopaminergic abnormalities in amino acid neurotransmission, particularly the glutamatergic system. Antidopaminergic antipsychotics modulate this system on several levels, as do mood stabilizers, including lamotrigine, topiramate and pregabaline. Recently, agonists at metabotropic glutamate receptors and glycine uptake inhibitors failed in large placebo-controlled trials for schizophrenia. Problems to overcome for successfully leveraging glutamatergic agents for schizophrenia are patient selection, focus on positive symptoms and late disease stages, and dose-response relationships. Because glutamate guides processes of brain development and maturation, clinical research should focus on the at-risk mental state or first-episode psychosis, address cognition and negative symptoms and use monotherapy designs in parallel to augmentation strategies.

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Effects of pregabalin on behavioral alterations induced by ketamine in rats

Abstract: This is the first study to investigate the effects of pregabalin using an animal model of psychosis. Furthermore, our results indicate that behavioral changes induced by ketamine in rats can be reversed with the use of pregabalin, suggesting its potential to treat psychotic symptoms.

Cited by 8 publications

References 14 publications

Cacna2d2 is an hnRNP H target of the striatal mRNA targetome and regulates methamphetamine behavior

Cacna2d2 is an hnRNP H target of the striatal mRNA targetome and regulates methamphetamine behavior

Animal Models of Psychosis: Current State and Future Directions

Glutamatergic agents for schizophrenia: current evidence and perspectives

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