Objective: Assessment of food reward by measuring preference for an environment previously paired with chocolate pellets after Exendin-4 administration to determine the impact of GLP-1 agonist on mesolimbic reward system
Materials & Equipment Checklist
6 items1 from ConductScience
Gather these items before starting the experiment. Check off items as you prepare.
Equipment2
Not specified • Not specified • Not specified • Not specified
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Protocol Steps
View Abstract
The glucagon-like peptide 1 (GLP-1) system is a recently established target for type 2 diabetes treatment. In addition to regulating glucose homeostasis, GLP-1 also reduces food intake. Previous studies demonstrate that the anorexigenic effects of GLP-1 can be mediated through hypothalamic and brainstem circuits which regulate homeostatic feeding. Here, we demonstrate an entirely novel neurobiological mechanism for GLP-1-induced anorexia in rats, involving direct effects of a GLP-1 agonist, Exendin-4 (EX4) on food reward that are exerted at the level of the mesolimbic reward system. We assessed the impact of peripheral, central, and intramesolimbic EX4 on two models of food reward: conditioned place preference (CPP) and progressive ratio operant-conditioning. Food-reward behavior was reduced in the CPP test by EX4, as rats no longer preferred an environment previously paired to chocolate pellets. EX4 also decreased motivated behavior for sucrose in a progressive ratio operant-conditioning paradigm when administered peripherally. We show that this effect is mediated centrally, via GLP-1 receptors (GLP-1Rs). GLP-1Rs are expressed in several key nodes of the mesolimbic reward system; however, their function remains unexplored. Thus we sought to determine the neurobiological substrates underlying the food-reward effect. We found that the EX4-mediated inhibition of food reward could be driven from two key mesolimbic structures—ventral tegmental area and nucleus accumbens—without inducing concurrent malaise or locomotor impairment. The current findings, that activation of central GLP-1Rs strikingly suppresses food reward/motivation by interacting with the mesolimbic system, indicate an entirely novel mechanism by which the GLP-1R stimulation affects feeding-oriented behavior.
1
Conditioned Place Preference Test Setup
Rats were exposed to an environment that was paired with chocolate pellets as a food reward
Not specifiedNot specified
Conditioned Place Preference - Mouse (Custom Order)
Matches: Conditioned Place Preference (CPP) apparatus
Note: This creates the conditioned association between environment and reward
View evidence from paper
“Food-reward behavior was reduced in the CPP test by EX4, as rats no longer preferred an environment previously paired to chocolate pellets.”
2
Exendin-4 Administration
EX4 was administered via peripheral, central, or intramesolimbic routes to assess impact on food reward behavior
Not specifiedNot specified
Note: Multiple administration routes were tested to determine site of action
View evidence from paper
“We assessed the impact of peripheral, central, and intramesolimbic EX4 on two models of food reward: conditioned place preference (CPP) and progressive ratio operant-conditioning.”
3
CPP Test Assessment
Measurement of rat preference for the environment previously paired with chocolate pellets after EX4 administration
Not specifiedNot specified
Note: Reduced preference indicates decreased rewarding value of food
View evidence from paper
“Food-reward behavior was reduced in the CPP test by EX4, as rats no longer preferred an environment previously paired to chocolate pellets.”
4
Progressive Ratio Operant-Conditioning Test
Assessment of motivated behavior for sucrose reward following peripheral EX4 administration
Not specifiedNot specified
Note: Measures the effort rats will expend to obtain food reward
View evidence from paper
“EX4 also decreased motivated behavior for sucrose in a progressive ratio operant-conditioning paradigm when administered peripherally.”
5
Mesolimbic Site Identification
Intramesolimbic EX4 administration to ventral tegmental area and nucleus accumbens to determine neurobiological substrates of food-reward suppression
Not specifiedNot specified
Note: Testing conducted without inducing concurrent malaise or locomotor impairment
View evidence from paper
“We found that the EX4-mediated inhibition of food reward could be driven from two key mesolimbic structures—ventral tegmental area and nucleus accumbens—without inducing concurrent malaise or locomotor impairment.”
