Contribution Of The Mesolimbic Pathway To Distraction From Ongoing Consummatory Behaviour: Implications For A Model Of Schizophrenia
thesisposted on 2019-02-14, 11:53 authored by Kate Z. Peters
Schizophrenia is a severe and debilitating condition affecting 1% of the population. Cognitive dysfunction in schizophrenia is poorly understood and there are no effective treatments. Current animal models, especially those characterising cognitive deficits, may not fully represent the deficits seen in patients. Disturbances in attention and increased distractibility are features of schizophrenia and increased distractibility may underlie deficits in the novel object recognition (NOR) task, which are seen in the subchronic phencyclidine (PCP) animal model. Here we developed a novel assay for distraction based on rats’ self-paced licking for saccharin. We used this assay in the subchronic PCP model to investigate distraction. In addition, as dopamine is implicated in the schizophrenic deficit and key dopaminergic areas are involved in consumption and distraction, we used fibre photometry to assess activity of mesolimbic circuits during this task. Our data demonstrate that rats pause ongoing licking in response to distracting stimuli but that these responses habituate quickly. Moreover, amphetamine increases distraction implicating the involvement of catecholamine neurotransmission. However, interestingly we found no differences in PCP treated rats although this may be due to limitations of this pharmacological model. Fibre photometry recordings revealed increases in ventral tegmental area (VTA) neural activity in response to licking and distracting stimuli, with greater increases in activity on trials where rats where distracted vs. non-distracted. Finally, we evaluated different strategies to specifically target dopamine neurons using a Cre-expressing tyrosine hydroxylase specific virus and using a transgenic Cre-expressing rat. In conclusion, we did not find clear differences in distraction within the PCP model, however, we characterised VTA responses associated with distractors and consumption in this paradigm. These results highlight the complex role of dopamine in maintaining ongoing appetitive and consummatory behaviours whilst also monitoring the environment for salient stimuli.