Perturbations in reward-related decision-making induced by reduced prefrontal cortical GABA transmission: Relevance for psychiatric disorders
| Autor: | Stan B. Floresco, Magdalen G. Schluter, Patrick T. Piantadosi, Shahin Khayambashi, Agnes Kutarna |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
Male
medicine.medical_specialty Reinforcement Schedule Decision Making Prefrontal Cortex Bicuculline gamma-Aminobutyric acid 03 medical and health sciences Cellular and Molecular Neuroscience Discrimination Psychological Risk-Taking 0302 clinical medicine Neurochemical Reward medicine Animals Rats Long-Evans GABA-A Receptor Antagonists Psychiatry Prefrontal cortex gamma-Aminobutyric Acid Pharmacology Motivation Antagonist Cognition medicine.disease Rats 030227 psychiatry Schizophrenia Conditioning Operant GABAergic Psychology Neuroscience 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | Neuropharmacology. 101:279-290 |
| ISSN: | 0028-3908 |
| DOI: | 10.1016/j.neuropharm.2015.10.007 |
| Popis: | The prefrontal cortex (PFC) is critical for higher-order cognitive functions, including decision-making. In psychiatric conditions such as schizophrenia, prefrontal dysfunction co-occurs with pronounced alterations in decision-making ability. These alterations include a diminished ability to utilize probabilistic reinforcement in guiding future choice, and a reduced willingness to expend effort to receive reward. Among the neurochemical abnormalities observed in the PFC of individuals with schizophrenia are alterations in the production and function of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA). To probe how PFC GABA hypofunction may contribute to alterations in cost/benefit decision-making, we assessed the effects GABAA-receptor antagonist bicuculline (BIC; 50 ng in 0.5 μl saline/hemisphere) infusion in the medial PFC of rats during performance on a series of well-validated cost/benefit decision-making tasks. Intra-PFC BIC reduced risky choice and reward sensitivity during probabilistic discounting and decreased the preference for larger rewards associated with a greater effort cost, similar to the behavioral sequelae observed in schizophrenia. Additional experiments revealed that these treatments did not alter instrumental responding on a progressive ratio schedule, nor did they impair the ability to discriminate between reward and no reward. However, BIC induced a subtle but consistent impairment in preference for larger vs. smaller rewards of equal cost. BIC infusion also increased decision latencies and impaired the ability to "stay on task" as indexed by reduced rates of instrumental responding. Collectively, these results implicate prefrontal GABAergic dysfunction as a key contributing factor to abnormal decision-making observed in schizophrenia and other neuropsychiatric conditions with similar neurobiological and behavioral alterations. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect