Effects Of Norepinephrine System On Risk

Risk-taking is characterized by behaviors conducted under uncertainty without effective contingency planning. These behaviors could result in some negative consequences and may induce some possible harm to oneself or others. Risk-taking is an aspect of the personality trait of impulsivity and is a feature of a series of psychiatric disorders, eg. Pathological Gambling. Previous studies indicate that pathological gamblers have higher baseline levels of norepinephrine and its metabolite3-methoxy-4-hydroxyphenylglycolin in Cerebrospinal Fluid. On the other hand, whether norepinephrinergic modulation could influence individuals’ risk-prone remains unknown.Twelve Sprague Dawley rats were used in this research (3of these were excluded for they were unable to finish the training session). Rats were individually housed and food restricted to85-90%of their free-feeding weight and given ad libitum access to water during the experiment. Behavioral testing was conducted in3operant chambers (29×29×26cm; Anilab--Associates) inclosed in sound-attenuating boxes. Experimental procedures were adapted from those of St Onge and Floresco (2010). The probability discounting task (PDT) consists of four blocks of10free-choice trials. A press on one lever always delivered a smaller reward (1pellet), while responding on the other occasionally delivered a lager reward (4pellets). The probability of delivering a larger reward decreased across the four blocks (100%,50%,25%and12.5%). In well-trained rats we assessed the effects of Norepinephrine (NE) reuptake inhibitor atomoxetine, as well as α1receptor antagonist prazosin and β receptor antagonist propranolol. The primary dependent measure of interest was the percentage of choices directed toward the large and risky lever for each block of free-choice trials, factoring trial omissions. Choice data was analyzed using two-way, repeated measures ANOVAS with treatment and trial block as within-subject factors. Response latency, the total number of food pellets delivered per session and trial omission data were analyzed with one-way repeated measures ANOVAS. We conducted a supplementary analysis to find out whether changes in choice behavior were due to variation in sensitivity to obtaining the larger reward (win-stay effect) or negative feedback (lose-shift effect).Nine rats demonstrated sensitivity to decreasing probabilities of the larger reward and stable baseline levels of choice pattern after an average of17±3days of training on the PDT. With all choice data, the effect of the total number of food pellets delivered per session and trial omission were always insignificant, indicating that the motivation of rats toward food did not change during the experiment. All dose of atomoxetine increased choice of the large/risky lever compared to vehicle. These increases were significantly higher on the50and25%blocks, reflecting a risky but not disadvantageous pattern of choice. Treatment with atomoxetine also significantly reduced lose-shift effect compared to vehicle. These two effects of atomoxetine on PDT were blocked by co-administration of β receptor antagonist propranolol rather than α1receptor antagonist prazosin. Furthermore, atomoxetine slightly increased response latency, while prazosin and propranolol did not influence this index.The main findings are:(1) atomoxetine. which increase NE release, produced a reliable increase in the preference for larger, yet risky rewards. This effect on choice was attributable to reduced lose-shift effect, which means that atomoxetine decreased negative feedback sensitivity in rats.(2) Moreover, treatment with atomoxetine altered choice only in50and25%blocks. The effects of atomoxetine on PDT were opposite with the impact induced by the Basolateral Amygdala (BLA) lesion. It suggests that altered NE function in BLA possibly accounts for risk-prone induced by atomoxetine.(3) Propranolol, but not prazosin, blocked risk-prone induced by atomoxetine in rats. In conclusion, NE has a critical role in mediating risk-taking of individuals. With elevated NE level making individuals more risk-prone, this effect is more likely mediated by β receptor.