Modulation of Reward Sensitivity by Acute and Chronic Thirst

States of physiological need motivate individuals to perform behaviors that restore homeostatic balance, such as seeking and consuming needed stimuli. This goal-directed behavior may be driven by modulation of the mesolimbic dopamine system by physiological state, altering reward sensitivity. While the effects of hunger on reward sensitivity have been widely researched, the effects of thirst have been largely unexplored. To determine the influence of acute and chronic states of thirst on reward sensitivity, I used a well validated intracranial self-stimulation (ICSS) rate frequency paradigm (Carlezon & Chartoff, 2007). First, subjects were acutely water deprived for 22-hours prior to the ICSS session. No effects of acute deprivation were detected on reward sensitivity. To further elucidate the circuitry underlying thirst sensing, the excitatory glutamatergic neurons of the subfornical organ, a key circumventricular organ involved in thirst sensing, were targeted with DREADDs and activated via administration of the exogenous ligand clozapine-N-oxide prior to ICSS. Again, no effects on reward sensitivity were detected. Finally, subjects underwent a five-day chronic water restriction protocol with daily ICSS sessions to determine the effects of sustained physiological need. Chronic water restriction significantly increased the stimulation threshold on days two, three, and four, indicating that subjects were significantly less sensitive to reward compared to baseline. This contrasts with prior literature demonstrating that in response to chronic food restriction, ICSS thresholds decrease and subjects display increased reward sensitivity. Together, these results indicate that changes in physiological state alter the responsiveness of reward circuitry. These shifts may prime responding to need fulfilling stimuli and invigorate goal directed behavior, but could also potentially exacerbate maladaptive behaviors to seek out other rewarding stimuli, such as seen in substance use and eating disorders. Future research should explore the interchange between need states and maladaptive behaviors.