Open Access Te Herenga Waka-Victoria University of Wellington
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Tobacco addiction in individuals with schizophrenia: A study in rats

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posted on 2021-11-16, 01:32 authored by Waterhouse, Uta

Schizophrenia as with most mental disorders develops due to an interaction of multiple genetic and environmental factors. Prenatal exposure to a maternal immuneactivation (MIA) is an environmental risk factor that can predispose offspring to develop schizophrenia later in life. The neurodevelopmental theory suggests that an immunechallenge during gestation can lead to long-lasting impairments such as in learning, memory,attention, or language (Brown & Patterson, 2012). Based on findings in human studies,prenatal exposure to a MIA has been utilized in preclinical research. Thus, the first aim of this study was to establish an animal model that generates subjects with schizophrenia-like cognitive impairments. To this end, a bacterial endotoxin, lipopolysaccharide (LPS) was used, which like most infectious agents, cannot cross the blood-placenta-barrier, yet reliably mimics an infection and initiates a MIA. Pregnant rats were subcutaneously (sc) injected with LPS (0.5 mg/kg) at one of three important neurodevelopmental time periods, gestation days (GD) 10/11, 15/16 or 18/19 (Fortier, Luheshi, & Boksa, 2007; Graciarena, Depino, & Pitossi, 2010). As individuals with schizophrenia commonly show deficits in multiple domains, three assessment paradigms were used to examine sensory and cognitive abilities in early and late adulthood. Tasks included prepulse inhibition to assess sensorimotor gating, latent inhibition to measure selective attention, and delayed non-matching to sample to evaluate working memory (WM).  Several theories have been suggested to explain high smoking incidence in schizophrenic patients (75-90%) compared to the general population (23%). The self-medication theory suggests high smoking rates amongst patients because nicotine, the primary addictive constituent in tobacco smoke, ameliorates some of the symptoms of the disorder such as cognitive deficits (D'Souza & Markou, 2012). Thus, the second aim of this study was to determine whether repeated experimenter and self-administered nicotine ameliorates or reduces schizophrenia-like cognitive deficits. Finally, the third aim was to investigate the common substrate theory, which suggests that shared underlying biological pathways may lead to increased susceptibility for an individual to develop both schizophrenia and tobacco addiction (Chambers, Krystal, & Self, 2001).  In conclusion, the findings of this study were coherently consistent and revealed that firstly, prenatal exposure to MIA early during foetal development led to long-lasting deficits in cognitive domains such as selective attention and WM. Secondly, supporting the self-medication theory, nicotine reversed MIA-induced cognitive impairments independent of the administration paradigm. Thirdly, increased responding rates for nicotine during self-administration acquisition in animals prenatally exposed to MIA were observed, yet there was no effect of prenatal treatment in dose response or progressive ratio testing. Thus, these findings only offer weak support for the common substrate theory.  Importantly, the findings of this study revealed that animals can be repeatedly assessed in these paradigms to examine the therapeutic efficacy of drugs and other treatments. This is of particular importance considering the lack of effective pharmacological treatments for cognitive deficits in schizophrenic patients.


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Date of Award



Te Herenga Waka—Victoria University of Wellington

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Author Retains Copyright

Degree Discipline


Degree Grantor

Te Herenga Waka—Victoria University of Wellington

Degree Level


Degree Name

Doctor of Philosophy

ANZSRC Type Of Activity code

970117 Expanding Knowledge in Psychology and the Cognitive sciences

Victoria University of Wellington Item Type

Awarded Doctoral Thesis



Victoria University of Wellington School

School of Psychology


Ellenbroek, Bart; Brennan, Katie