ABSTRACT
Forced choice between alternative options of unpredictable outcome is a complex task that requires continual update of the value associated with each option. Prefrontal areas such as the orbitofrontal cortex (OFC) have been shown to play a major role in performance on ambiguous decision-making tasks with substantial risk component, broadly named as "gambling tasks." We have recently demonstrated that rats display complex decision-making behavior in a rodent gambling task based on serial choices between rewards of different value and probability. This rodent task retains many of the key characteristics of the human Iowa Gambling Task (IGT), and performance in this novel task is also disrupted by OFC or amygdalar lesioning. In the present study we addressed if rat models of chronic pain would have impaired performance in this gambling task, since it is already known that the IGT response patterns of human pain patients are comparable to individuals with OFC lesions. We found that animals with a monoarthritic inflammatory model of chronic pain systematically preferred the lever associated with larger but infrequent rewards. In addition, we measured the neurochemical content of the OFC, amygdala and nucleus accumbens using HPLC, and found that in prolonged chronic pain animals there was a decrease in the tonic levels of dopamine, DOPAC (3,4-hydroxyphenyl-acetic acid) and 5-HIAA (5-hydroxyindole-3-acetic acid) in the OFC. This is the first report of the effect of chronic pain in rat decision-making processes and supports the notion that pain may have profound effects on the functioning of the reward-aversion circuitry relevant to strategic planning.
Subject(s)
Cognition , Decision Making , Pain/psychology , Prefrontal Cortex/physiopathology , 3,4-Dihydroxyphenylacetic Acid/metabolism , Amygdala/metabolism , Animals , Chronic Disease , Disease Models, Animal , Dopamine/metabolism , Freund's Adjuvant , Gambling , Hydroxyindoleacetic Acid/metabolism , Male , Neuropsychological Tests , Nucleus Accumbens/metabolism , Pain/chemically induced , Prefrontal Cortex/metabolism , Rats , Rats, Sprague-Dawley , Reinforcement Schedule , Reward , Time FactorsABSTRACT
PURPOSE: Glaucoma is an optic neuropathy characterized by a high intraocular pressure (IOP), alterations in optic nerve head, and loss of visual field that could lead to bilateral blindness. Serotonin (5-HT) is a biogenic monoamine that is synthesized from hydroxylation of tryptophan and acts by three ways, dissemination, metabolism, and reuptake in synaptic cleft through specific systems of the membrane. The purpose of this study is to evaluate the 5-HT and 5-HIAA (5-hydroxiindolacetic acid) levels in the aqueous humor of patients with primary open-angle glaucoma (POAG). METHODS: We performed a case-control study, and the patients recruited were classified into two groups, 1) 30 patients with POAG (GG) and 2) 30 patients with cataracts (CG), who acted as the controls. Aqueous humor samples of each patient were obtained by paracentesis at the beginning of the surgical procedures. 5-HT and 5-HIAA levels were determined by high performance liquid chromatography (HPLC) with electrochemical detection. RESULTS: There were no statistical differences between age (71.3 +/- 7.2 years in GG, 73.5 +/- 9.0 years in CG; p=0.2581) or gender (sex ratio 0.765 in GG and 0.667 in CG). 5-HT levels were lower in GG, but this difference was not significant (p=0.820). We observed a statistically significant higher level of 5-HIAA in GG (p=0.001). The 5-HT turnover (5-HIAA/5-HT) were higher in GG than in CG (p<0.05), but the difference was not significant (p=0.598). CONCLUSIONS: The level of 5-HT was lower in GG patients, and the level of 5-HIAA was higher in GG patients than in CG patients.
