Mu opioid receptor (MOR) signaling in the nucleus accumbens (NAcc) elicits marked increases in the consumption of palatable tastants. However, the mechanism and circuitry underlying this effect are not fully understood. Multiple downstream target regions have been implicated in mediating this effect but the role of the ventral pallidum (VP), a primary target of NAcc efferents, has not been well defined. To probe the mechanisms underlying increased consumption, we identified behavioral changes in licking patterns following NAcc MOR stimulation. Because the temporal structure of licking reflects the physiological substrates modulating consumption, these measures provide a useful tool in dissecting the cause of increased consumption following NAcc MOR stimulation. Next, we used a combination of pharmacological inactivation and lesions to define the role of the VP in hyperphagia following infusion of the MOR-specific agonist [D-Ala2, N-MePhe4, Gly-ol]-enkephalin (DAMGO) into the NAcc. In agreement with previous studies, results from lick microstructure analysis suggest that NAcc MOR stimulation augments intake through a palatability-driven mechanism. Our results also demonstrate an important role for the VP in normal feeding behavior: pharmacological inactivation of the VP suppresses baseline and NAcc DAMGO-induced consumption. However, this interaction does not occur through a serial circuit requiring direct projections from the NAcc to the VP. Rather, our results indicate that NAcc and VP circuits converge on a common downstream target that regulates food intake.
Lithium is a drug widely employed for the treatment of bipolar disorder owing to its high efficacy in mood management and suicide prevention. However, this efficacy is often undermined by misdosing and nonadherence, and diligent drug monitoring is required during treatment. Standard lithium monitoring involves invasive blood collections and laboratory analysis with low time granularity. Recent advances in sensor technology have enabled the development of personalized drug-monitoring devices that analyze biomarker information noninvasively. Herein, based on the fact that the analyte partition onto the fingertip with a high flux, a touch-based noninvasive monitoring modality for managing lithium pharmacotherapy is devised. The system is built based on a thin organohydrogel-mounted lithium ion-selective electrode (TOH-ISE). The TOH coating provides a stable environment for sensing. Through the utilization of a water/glycerol bi-solvent matrix, the gel exhibits dehydration-resist properties, rendering a controlled micro-environment for ISE conditioning, and subsequently minimizing signal drift. To illustrate the clinical application of the solution, the system is tested on a subject prescribed lithium. The system successfully detected the increase in circulating drug levels following medication intake. Collectively, the results indicate the devised solution is capable to facilitate lithium adherence monitoring and has broader potential for optimizing lithium pharmacotherapy.
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