Neonatal phencyclidine as a model of sex-biased schizophrenia symptomatology in adolescent mice

Dutra-Tavares, Ana Carolina; Souza, Thainá Pereira de; Silva, Juliana O.; Semeão, Keila A.; Mello, Fábio Fernandes; Filgueiras, Cláudio C.; Ribeiro‐Carvalho, Anderson; Manhães, Alex C.; Abreu‐Villaça, Yael

doi:10.1007/s00213-023-06434-3

Cited by 3 publications

(3 citation statements)

References 118 publications

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“…As discussed below, this consistent effect might be associated with the earlier onset and higher severity of symptoms identified in male patients diagnosed with SCHZ when compared to females [14,63]. Sex-biased effects were also identified in animal models of the disorder [63], even during adolescence [64].…”

Section: Males Mpfc Interactome Map Of Pcpnic Micementioning

confidence: 86%

“…This is a very distinct pattern from that identified in males, in which all proteins were downregulated. Considering previous evidence of sex differences in animal models of SCHZ and in SCHZ patients [14,63,64], it is possible that the pattern identified in females is related to a tentative compensatory effect. In case similar events occur in patients, those could play a role in the less severe negative and cognitive symptomatology and course of the disorder described in SCHZ women [95].…”

Section: Female Mpfc Interactome Map Of Pcpnic Micementioning

confidence: 97%

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Nicotine Exposure in a Phencyclidine-Induced Mice Model of Schizophrenia: Sex-Selective Medial Prefrontal Cortex Protein Markers of the Combined Insults in Adolescent Mice

Rodríguez-Vega,

Dutra-Tavares,

Souza

et al. 2023

IJMS

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Tobacco misuse as a comorbidity of schizophrenia is frequently established during adolescence. However, comorbidity markers are still missing. Here, the method of label-free proteomics was used to identify deregulated proteins in the medial prefrontal cortex (prelimbic and infralimbic) of male and female mice modelled to schizophrenia with a history of nicotine exposure during adolescence. Phencyclidine (PCP), used to model schizophrenia (SCHZ), was combined with an established model of nicotine minipump infusions (NIC). The combined insults led to worse outcomes than each insult separately when considering the absolute number of deregulated proteins and that of exclusively deregulated ones. Partially shared Reactome pathways between sexes and between PCP, NIC and PCPNIC groups indicate functional overlaps. Distinctively, proteins differentially expressed exclusively in PCPNIC mice reveal unique effects associated with the comorbidity model. Interactome maps of these proteins identified sex-selective subnetworks, within which some proteins stood out: for females, peptidyl-prolyl cis-trans isomerase (Fkbp1a) and heat shock 70 kDa protein 1B (Hspa1b), both components of the oxidative stress subnetwork, and gamma-enolase (Eno2), a component of the energy metabolism subnetwork; and for males, amphiphysin (Amph), a component of the synaptic transmission subnetwork. These are proposed to be further investigated and validated as markers of the combined insult during adolescence.

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Section: Males Mpfc Interactome Map Of Pcpnic Micementioning

confidence: 86%

Section: Female Mpfc Interactome Map Of Pcpnic Micementioning

confidence: 97%

Nicotine Exposure in a Phencyclidine-Induced Mice Model of Schizophrenia: Sex-Selective Medial Prefrontal Cortex Protein Markers of the Combined Insults in Adolescent Mice

Rodríguez-Vega,

Dutra-Tavares,

Souza

et al. 2023

IJMS

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“…Several experimental studies have since corroborated this notion, demonstrating drug effects that mirror both the positive symptoms (e.g., hallucinations, delusions, paranoia, and disorganized thinking) and negative symptoms (e.g., affective flattening, anhedonia, attentional and cognitive impairment) characteristic of schizophrenia [ 38 , 39 , 40 ]. Current major neurobiological theories of schizophrenia trace their roots back to the effects of various substances: the serotonergic model stemmed from observations of lysergic acid diethylamide (LSD) [ 41 ], the dopamine hypothesis emerged from studies on amphetamines, and the glutamatergic model was influenced by research on phencyclidine (PCP) and ketamine [ 42 , 43 , 44 , 45 , 46 ]. More recently, interest has grown in the role of endocannabinoids, spurred by the effects of cannabis [ 47 , 48 , 49 ].…”

Section: Introductionmentioning

confidence: 99%

Rethinking Mental Automatism: De Clérambault’s Theory in the Age of Novel Psychoactive Drugs: Psychotropic Effects and Synthetic Psychosis

Ricci,

Maina,

Martinotti

2024

Healthcare

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The widespread use of novel psychoactive substances (NPSs)—defined as new narcotic or psychotropic agents not classified under the Single Convention on Narcotic Drugs of 1961 or the Convention on Psychotropic Substances of 1971—poses a significant challenge to contemporary mental health paradigms due to their impact on psychiatric disorders. This study revisits and expands upon the theory of mental automatism as proposed by Gaëtan Gatian de Clérambault, aiming to elucidate the psychopathological mechanisms underlying substance-induced psychoses (SIP) and their distinction from non-induced psychoses (schizophrenia and related disorders). Through a phenomenological and clinical investigation, we explore the relevance of mental automatism in the development of toxic psychoses, drawing upon the historical and contemporary literature. This research highlights the psychopathological distinctions between induced and non-induced psychoses and the transition mechanisms from acute to chronic psychosis states. De Clérambault’s theory, supplemented by Janet, Jackson, and Bonhoeffer’s contributions, provides a foundational framework for understanding the genesis of SIP. Our findings suggest that NPS consumption, particularly among adolescents and psychiatric patients, significantly correlates with increased risks of SIP, marked by a transition to chronicity influenced by biological lesions triggered by substance use. Furthermore, we propose a comprehensive framework for SIP, integrating mental automatism, psychopathological distinctions, and transition mechanisms. This framework aims to refine diagnostic criteria and therapeutic approaches, addressing gaps in clinical practice and research. The study underscores the need for a nuanced understanding of SIP, advocating for a paradigm shift in psychiatric assessment and treatment approaches to better address the complexities of substance-induced mental health disorders.

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Nicotine’s Effects on Schizophrenia-like Symptoms in a Mice Model: Time Matters

Dutra-Tavares,

Couto,

Souza

et al. 2024

Brain Sciences

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Tobacco consumption in schizophrenia (SCHZ) patients is highly prevalent. Data support the occurrence of sequential events during comorbidity establishment, and both smoking first, SCHZ second and SCHZ first, smoking second sequences have been proposed. To investigate whether these two possibilities lead to distinct outcomes of comorbidity, we used a phencyclidine-induced SCHZ model and nicotine exposure as a surrogate of smoking. C57Bl/6 mice were submitted to a protocol that either began with 4 days of phencyclidine exposure or 4 days of nicotine exposure. This period was followed by 5 days of combined phencyclidine + nicotine exposure. Locomotor sensitization and pre-pulse inhibition (PPI) were assessed due to their well-known associations with SCHZ as opposed to rearing, an unrelated behavior. Nicotine priming potentiated phencyclidine-evoked sensitization. However, nicotine exposure after SCHZ modeling did not interfere with phencyclidine’s effects. In the PPI test, nicotine after SCHZ modeling worsened the phencyclidine-evoked deficiency in males. In contrast, nicotine priming had no effects. Regarding rearing, nicotine priming failed to interfere with phencyclidine-mediated inhibition. Similarly, phencyclidine priming did not modify nicotine-mediated inhibition. The present results indicate that the sequence, either SCHZ-first or nicotine-first, differentially impacts comorbidity outcomes, a finding that is relevant for the identification of mechanisms of nicotine interference in the neurobiology of SCHZ.

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Neonatal phencyclidine as a model of sex-biased schizophrenia symptomatology in adolescent mice

Cited by 3 publications

References 118 publications

Nicotine Exposure in a Phencyclidine-Induced Mice Model of Schizophrenia: Sex-Selective Medial Prefrontal Cortex Protein Markers of the Combined Insults in Adolescent Mice

Nicotine Exposure in a Phencyclidine-Induced Mice Model of Schizophrenia: Sex-Selective Medial Prefrontal Cortex Protein Markers of the Combined Insults in Adolescent Mice

Rethinking Mental Automatism: De Clérambault’s Theory in the Age of Novel Psychoactive Drugs: Psychotropic Effects and Synthetic Psychosis

Nicotine’s Effects on Schizophrenia-like Symptoms in a Mice Model: Time Matters

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