The Long-term Effects of Chronic Antipsychotic Drug Treatment in Juvenile Rats on Adult Behavioural Attributes, Dopamine and Serotonin Neurotransmitter Systems

The prescription and use of antipsychotic drugs (APDs) to treat various mental illnesses and behavioural disorders in children and adolescents has exponentially increased in recent years on a global scale. This significant increase in rates of use across both male and female sexes is despite a limited knowledge of what the long-term effects of early APD treatment are. With critical neurodevelopmental phases well-known to extend through this juvenile time period, there is the potential that exposure to the potent actions of APDs on numerous multifunctional neurotransmitter (NT) systems may alter brain topography on a long-term and/or permanent basis. Furthermore, alterations to NT systems including dopamine (DA) and serotonin (5-HT) have previously been heavily implicated in both the pathogenesis of mental illness, and known to play significant roles in behavioural attributes such as activity levels and anxiety. With the second generation APDs aripiprazole, olanzapine and risperidone three of the most commonly prescribed to the juvenile population, and the therapeutic effects of APDs predominantly based on a partial agonist and/or antagonist mechanism of action on DA and 5-HT receptors and hence modulation of NT signal, this thesis investigated the long-term effects of juvenile APD treatment during this critical neurodevelopmental time period on adult behavioural attributes, and subsequently uncovered potential longterm alterations to the DA and 5-HT NT system in the adult brain across both male and female cohorts.