Effects of prenatal immune activation on amphetamine-induced addictive behaviors: Contributions from animal models

Borçoi, Aline Ribeiro; Patti, Camilla L.; Zanin, Karina A.; Hollais, A.W.; Santos-Baldaia, Renan; Ceccon, L.M.B.; Berro, Laís F.; Wuo-Silva, Raphael; Grapiglia, S.B.; Ribeiro, Lucilene Arilho; Lopes-Silva, Leonardo B.; Frussa‐Filho, Roberto

doi:10.1016/j.pnpbp.2015.05.015

Cited by 23 publications

(16 citation statements)

References 69 publications

(79 reference statements)

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“… 69 , 70 The findings from our preclinical model suggests that maternal infection could represent one of the neurodevelopmental factors triggering the appearance of an addiction-prone phenotype in patients with schizophrenia, although epidemiological data supporting such an association are missing thus far. Yet, our findings are in line with the previous work in other schizophrenia-relevant animal models documenting altered responses to natural or drug rewards, including models that are based on neonatal ventral hippocampal lesion, 71 , 72 , 73 prenatal infection 74 , 75 or mutant expression of DISC1. 76 Altogether, these observations provide support for the theory that the predilection for addictive behavior would be ingrained in schizophrenia neuropathology.…”

Section: Discussionsupporting

confidence: 91%

Abnormal context–reward associations in an immune-mediated neurodevelopmental mouse model with relevance to schizophrenia

2015

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Impairments in central reward processing constitute an important aspect of the negative symptoms of schizophrenia. Despite its clinical relevance, the etiology of deficient reward processing in schizophrenia remains largely unknown. Here, we used an epidemiologically informed mouse model of schizophrenia to explore the effects of prenatal immune activation on reward-related functions. The model is based on maternal administration of the viral mimic PolyI:C and has been developed in relation to the epidemiological evidence demonstrating enhanced risk of schizophrenia and related disorders following prenatal maternal infection. We show that prenatal immune activation induces selective deficits in the expression (but not acquisition) of conditioned place preference for a natural reward (sucrose) without changing hedonic or neophobic responses to the reward. On the other hand, prenatal immune activation led to enhanced place preference for the psychostimulant drug cocaine, while it attenuated the locomotor reaction to the drug. The prenatal exposure did not alter negative reinforcement learning as assessed using a contextual fear conditioning paradigm. Our findings suggest that the nature of reward-related abnormalities following prenatal immune challenge depends on the specificity of the reward (natural reward vs drug of abuse) as well as on the valence domain (positive vs negative reinforcement learning). Moreover, our data indicate that reward abnormalities emerging in prenatally immune-challenged offspring may, at least in part, stem from an inability to retrieve previously established context–reward associations and to integrate such information for appropriate goal-directed behavior.

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Section: Discussionsupporting

confidence: 91%

Abnormal context–reward associations in an immune-mediated neurodevelopmental mouse model with relevance to schizophrenia

2015

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“…In contrast to this, a previous study using prenatal poly I : C treatment found an increased amphetamine‐induced behavioral sensitization as well as conditioned place preference (Borcoi et al ), although self‐administration was not investigated. The difference between these two studies may be related to differences in the MIA procedure (LPS versus poly I : C), the drug used or the paradigms investigated.…”

Section: Discussionmentioning

confidence: 63%

Nicotine self‐administration reverses cognitive deficits in a rat model for schizophrenia

2017

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High comorbidity between schizophrenia and tobacco addiction has been well established. Explanatory theories include nicotine as a cognitive enhancer ameliorating symptoms of schizophrenia and underlying shared substrates increasing susceptibility to addiction in these individuals. To test these non-mutually exclusive theories, the maternal immune activation (MIA) model was utilized. To this end, pregnant Sprague Dawley rats were subcutaneously injected with a bacterial endotoxin, lipopolysaccharide (0.5 mg/kg), on gestation days 10 and 11. Selective attention and working memory in adult male offspring were subsequently assessed using the latent inhibition and delayed non-matching to sample paradigms both before and after nicotine or saline self-administration. MIA led to deficits in both latent inhibition and delayed non-matching to sample in male offspring. Further, these animals showed a small but significantly increased responding for nicotine during self-administration acquisition, although there was no difference in dose-response effect or in progressive ratio testing. However, nicotine, but not saline self-administration, significantly ameliorated the cognitive deficits induced by MIA. While the male offspring of mothers prenatally exposed to lipopolysaccharide was only slightly more sensitive to the reinforcing effects of nicotine, after self-administration, the MIA-induced cognitive deficits significantly improved. These data lend support for the self-medication hypothesis of schizophrenia.

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Section: Psychostimulants: Amphetaminementioning

confidence: 99%

“…Altered dopaminergic function is observed in the Poly I:C model, where prenatal Poly I:C treatment in mice enhances locomotor sensitization and stereotyped behaviour to repeated amphetamine administration, compared to control offspring [89]. Also, amphetamine CPP is greater in Poly I:C offspring compared to control offspring, suggesting heightened reward for amphetamine [89]. Similarly, prenatally MAM-treated rats show a greater stereotyped behavioural response to an amphetamine challenge dose than controls, suggesting greater expression of amphetamine sensitization following prenatal MAM treatment [90].…”

Section: Psychostimulants: Amphetaminementioning

confidence: 99%

“…Despite elevated cocaine context-reward associations, Poly I:C treated mice exhibit reduced cocaine-induced locomotor activity, which may indicate lower dopamine transporter or dopamine receptor availability in brain regions such as the VTA or striatum [91]. Prenatal Poly I:C treatment in rats also enhances cross-sensitization to cocaine after behavioural sensitization to amphetamine, suggesting elevated susceptibility to other stimulant drugs following repeated amphetamine administration [89]. Interestingly, Poly I:C mice do not exhibit place preference for a natural reward, sucrose, where control mice do, yet learning about an aversive stimulus (i.e.…”

Section: Psychostimulants: Cocainementioning

confidence: 99%

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Schizophrenia and drug addiction comorbidity: recent advances in our understanding of behavioural susceptibility and neural mechanisms

Menne

Chesworth

2020

Neuroanatomy and Behaviour

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Schizophrenia is a severe psychiatric disorder which is worsened substantially by substance abuse/addiction. Substance abuse affects nearly 50% of individuals with schizophrenia, extends across several drug classes (e.g. nicotine, cannabinoids, ethanol, psychostimulants) and worsens overall functioning of patients. Prominent theories explaining schizophrenia and addiction comorbidity include the primary addiction hypothesis (i.e. schizophrenia susceptibility primes drug reward circuits, increasing drug addiction risk following drug exposure), the two-hit hypothesis (i.e. drug abuse and other genetic and/or environmental risk factors contribute to schizophrenia development) and the self-medication hypothesis (i.e. drug use alleviates schizophrenia symptoms). Animal models can be used to evaluate the utility and validity of these theories. Since this literature was last reviewed by Ng and colleagues in 2013 [Neurosci Biobehav Rev, 37(5)], significant advances have been made to our understanding of schizophrenia and substance abuse comorbidity. Here we review advances in the field since 2013, focussing on two key questions: 1) Does schizophrenia susceptibility increase susceptibility to drug addiction (assessing the primary addiction hypothesis), and 2) Do abused drugs exacerbate or ameliorate schizophrenia symptoms (assessing the two-hit hypothesis and the self-medication hypothesis). We addressed these questions using data from several schizophrenia preclinical models (e.g. genetic, lesion, neurodevelopmental, pharmacological) across drug classes (e.g. nicotine, cannabinoids, ethanol, psychostimulants). We conclude that addiction-like behaviour is present in several preclinical schizophrenia models, and drugs of abuse can exacerbate but also ameliorate schizophrenia-relevant behaviours. These behavioural changes are associated with altered receptor system function (e.g. dopaminergic, glutamatergic, GABAergic) critically implicated in schizophrenia and addiction pathology.

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Effects of prenatal immune activation on amphetamine-induced addictive behaviors: Contributions from animal models

Cited by 23 publications

References 69 publications

Abnormal context–reward associations in an immune-mediated neurodevelopmental mouse model with relevance to schizophrenia

Abnormal context–reward associations in an immune-mediated neurodevelopmental mouse model with relevance to schizophrenia

Nicotine self‐administration reverses cognitive deficits in a rat model for schizophrenia

Schizophrenia and drug addiction comorbidity: recent advances in our understanding of behavioural susceptibility and neural mechanisms

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