Assessing the Effect of Chronic Dopamine Receptor 2 Blockade as a Potential Model of Secondary Negative Symptoms in Rats Using the FR5/Chow Feeding Choice Task

Haloperidol, a dopamine (DA) D2 receptor antagonist, is an antipsychotic drug which is commonly used to treat schizophrenia and other psychiatric disorders. These disorders are often characterized by elevated striatal dopamine, which is speculated to have a role in producing positive symptoms such as hallucinations, delusions, and paranoia, as well as symptoms related to motivational salience and reward prediction. Individuals with schizophrenia also exhibit negative symptoms, such as amotivation, anergia, fatigue, and apathy among others. While some negative symptoms of schizophrenia are inherent to the pathophysiology, other negative symptoms are hypothesized to be partially induced by chronic exposure to antipsychotic treatments, such as haloperidol. This may be due to the blockade of DA receptors in some striatal areas of the brain, as well as D2 receptor density changes as a result of chronic exposure to a DA D2 antagonist. Over the past several decades, effort-based decision making tasks have been used to model motivational symptoms of psychiatric disorders in rodents. Previous experiments have shown that DA depletions or antagonism in the nucleus accumbens (NAc) reduces the amount of effort animals will exert, biasing them towards the low-effort chow alternative. To elucidate the role of chronic DA D2 receptor antagonism on motivation in rats, this study assessed the impact of chronic haloperidol administration on cost-effort computing using the FR5/chow feeding choice task. It was hypothesized that we would see a bias in the group of rats receiving haloperidol towards the low-effort alternative. This study will be beneficial in understanding the impact of chronic, steady state administration of antipsychotics on cost-effort computing and effort-related choice behaviors, with further implications for treatment of schizophrenic patients