Dopaminergic Modulation of Risk-based
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چکیده
Psychopharmacological studies have implicated the mesolimbic dopamine (DA) system in the mediation of cost/benefit evaluations about effort-related costs associated with larger rewards. However, the role of DA in risk-based decision making remains relatively unexplored. The present study investigated how systemic manipulations of DA transmission affect risky choice assessed with a probabilistic discounting task. Over discrete trials, rats between two levers; a press on the “small/certain” lever always delivered one reward pellet, whereas a press on the other, “large/risky” lever delivered four pellets, but the probability of receiving reward decreased across the four trial blocks (100%, 50%, 25%, 12.5%). In separate groups of well-trained rats we assessed the effects of the DA releaser amphetamine, as well as receptor selective agonists and antagonists. Amphetamine consistently increased preference for the large/risky lever; an effect that was blocked or attenuated by coadministration of either D1 (SCH23390) or D2 (eticlopride) receptors antagonists. Blockade of either of these receptors alone induced risk aversion. Conversely, stimulation of D1 (SKF81297) or D2 (bromocriptine) receptors also increased risky choice. In contrast, activation of D3 receptors with PD128,907 induced risk aversion. Likewise, D3 antagonism with nafadotride potentiated the amphetamine-induced increase in risky choice. Blockade or stimulation of D4 receptors did not reliably alter patterns of choice. These findings indicate that DA plays a critical role in mediating risk-based decision making, where increased activation of D1 and D2 receptors biases choice towards larger, probabilistic rewards, whereas D3 receptors appear to exert opposing effects on this form of decision making.
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