Altered dopamine D2 receptor function and binding in obese OLETF rat.

Area of Science:

• Neuroscience
• Obesity Research
• Pharmacology

Background:

• Reduced D2-like receptor (D2R) binding is observed in obese individuals and drug addicts.
• Shared neural pathways for natural and drug rewards raise questions about D2R's role in overeating and obesity.

Purpose of the Study:

• Investigate D2R density and quinpirole's effects on locomotor activity and sucrose intake in diet-induced obese rats (OLETF).
• Examine the link between altered D2R signaling and sucrose overconsumption in obesity.

Main Methods:

• Utilized Otsuka Long Evans Tokushima Fatty (OLETF) rats, a model for diet-induced obesity, and lean controls (LETO).
• Measured [125I]-iodosulpride binding to assess D2R density in the accumbens shell.
• Administered the D2R agonist quinpirole (0.05, 0.5 mg/kg) to evaluate effects on locomotor activity and sucrose intake.

Main Results:

• OLETF rats exhibited significantly lower D2R binding in the accumbens shell compared to LETO rats (-16%).
• Low-dose quinpirole reduced locomotor activity more in OLETF rats.
• Both quinpirole doses significantly decreased sucrose intake in OLETF rats, but not in LETO rats.

Conclusions:

• Obese OLETF rats display altered D2R signaling, mirroring patterns seen in drug-induced sensitization.
• Findings suggest a connection between D2R signaling alterations and heightened sucrose preference in diet-induced obesity.