Background: The main aim of the studies in this thesis is to provide insights into the neonatal phencyclidine (PCP) induced deficits in male and female rats as a neurodevelopmental animal model of schizophrenia. Methods: Both male and female rats were treated with neonatal PCP on postnatal days (PNDs) 7,9 and 11 or vehicle, followed by weaning on PND 21-22. The rats were then tested in behavioural paradigms such as novel object recognition, spatial memory and social interaction in their adolescent and adult stages and were also tested with acute treatment of typical and atypical antipsychotic agents. Results: Neonatal PCP treatment (10 & 20 mg/kg in males and 10 mg/kg in females; once a day for 3 days on PND 7,9 and 11) caused novel object recognition and spatial memory impairment in male and female rats both in the adolescent (PND35-56) and in the adult stages (PND>56) (chapter 2) and robust deficits in social interaction behaviours in the adolescent stage. The SI deficits were observed in adulthood in female but not in male rats thereby establishing a sex-specific social behavioural deficit (chapter 3). The object memory and social interaction deficits induced by neonatal PCP treatment were reversed following acute risperidone but not haloperidol. Finally, the temporal profile of this treatment regime was investigated and the male and female animals were tested on PND 190 and PND 365. The animals did not have any challenge dose of PCP during their testing stage. The result showed that there was significant deficit in object and spatial recognition memory in both male and female animals at both time points, thereby establishing enduring deficits. Conclusion: Given the heterogeneity of the schizophrenic disorder and its complex aetiology, it is understandably difficult to find animal models that completely mimic most or all of the symptoms associated with the disorder. However, data from the studies in this thesis support the use of neonatal PCP as a valid animal model of cognitive and negative symptoms, and explores the effect of antipsychotics in understanding the model. Also, in light of the efficacy of neonatal PCP to produce robust object, spatial memory and social interaction deficits in rats, it appears that this model may be a useful tool to investigate the potential of novel therapeutic candidates that may help improve therapy and understand the illness.

Background: The main aim of the studies in this thesis is to provide insights into the neonatal phencyclidine (PCP) induced deficits in male and female rats as a neurodevelopmental animal model of schizophrenia. Methods: Both male and female rats were treated with neonatal PCP on postnatal days (PNDs) 7,9 and 11 or vehicle, followed by weaning on PND 21-22. The rats were then tested in behavioural paradigms such as novel object recognition, spatial memory and social interaction in their adolescent and adult stages and were also tested with acute treatment of typical and atypical antipsychotic agents. Results: Neonatal PCP treatment (10 & 20 mg/kg in males and 10 mg/kg in females; once a day for 3 days on PND 7,9 and 11) caused novel object recognition and spatial memory impairment in male and female rats both in the adolescent (PND35-56) and in the adult stages (PND>56) (chapter 2) and robust deficits in social interaction behaviours in the adolescent stage. The SI deficits were observed in adulthood in female but not in male rats thereby establishing a sex-specific social behavioural deficit (chapter 3). The object memory and social interaction deficits induced by neonatal PCP treatment were reversed following acute risperidone but not haloperidol. Finally, the temporal profile of this treatment regime was investigated and the male and female animals were tested on PND 190 and PND 365. The animals did not have any challenge dose of PCP during their testing stage. The result showed that there was significant deficit in object and spatial recognition memory in both male and female animals at both time points, thereby establishing enduring deficits. Conclusion: Given the heterogeneity of the schizophrenic disorder and its complex aetiology, it is understandably difficult to find animal models that completely mimic most or all of the symptoms associated with the disorder. However, data from the studies in this thesis support the use of neonatal PCP as a valid animal model of cognitive and negative symptoms, and explores the effect of antipsychotics in understanding the model. Also, in light of the efficacy of neonatal PCP to produce robust object, spatial memory and social interaction deficits in rats, it appears that this model may be a useful tool to investigate the potential of novel therapeutic candidates that may help improve therapy and understand the illness.

Temporal and spatial cognition constitute basic elements of the cognitive function. Both of these competences are important for the individual's orientation and survival and there are likely to be different interactions between them. Perception of time, unlike spatial navigation and memory, is less explored. Impairments of interval timing occur in many neurodegenera- tive and neuropsychiatric disorders. According to current studies it is evident that timing is impaired even in patients with schizophrenia, but the results are still ambiguous. The aim of our work was to test the AAPA task in the time-place integration in the ani- mal model of schizophrenia. In the future, it could help to clarify the impairments of the time perception in patients with schizophrenia. In contrast to the classic AAPA task, our version included alternating of phases of light and darkness. The assumption of the experiment was that the solution of the task by rats in the dark is more dependent on the timing strategy than the solution of the task during the light, which is dependent on the spatial orientation. In the first phase of the experiment, the rats adopted both strategies - spatial (during the light phase of the session) and timing (during the dark phase). In the next phase of the experiment, we tested the animal...

Disruption of cognitive abilities such as learning, memory and spatial navigation accompanies a number of neuropsychiatric disorders including schizophrenia. Cognitive symptoms are also most difficult to target by available pharmacotherapy.. Behavioral and molecular evidence point to a disruption of NMDA receptors and glutamatergic and dopaminergic neurotransmission. Impaired cognitive coordination has been proposed as a core cognitive deficit in schizophrenia. Non- competitive NMDAR antagonists are used to model schizophrenia- related symptoms in humans and in experimental animals. Place avoidance on a rotating arena is used to model cognitive functions disrupted in an animal model of schizophrenia. The goal of this thesis is to show whether the deficit in place avoidance is due to disrupted cognitive coordination or another effect of NMDAR antagonism such as hyperlocomotion, general learning deficit, or altered sensitivity.