Oxytocin action in the ventral tegmental area affects sucrose intake

Abstract

Brain oxytocin is known to play a role in the control of food intake, and recent studies suggest that stimulation of central oxytocin receptors selectively suppresses carbohydrate intake. The specific oxytocin projection sites and receptor populations involved in this response are as yet unidentified. We hypothesized that oxytocin receptors in the ventral tegmental area (VTA) may play a role in limiting sucrose intake, because the VTA is known to influence palatable food intake. We first performed a dose response study in which we observed that intra-VTA oxytocin injection significantly suppressed intake of a 10% sucrose solution during a 30-min test session by 13.35-20.5% relative to vehicle treatment. Doses of intra-VTA oxytocin that suppressed sucrose intake had no effect on water intake. Next we examined the effects of two oxytocin receptor antagonists, (d(CH2)5(1),Tyr(Me)(2),Orn(8))-Oxytocin (OVT) and L-368,899. Each of these antagonists significantly increased 10% sucrose intake by 17-20.5% relative to vehicle when delivered directly into the VTA, at doses subthreshold for effect if injected into the cerebral ventricles. Finally, we observed that the effect of intra-VTA oxytocin to suppress 10% sucrose intake was significantly attenuated by pretreatment with L-368,899, supporting the suggestion that the VTA oxytocin treatment suppresses intake through action at oxytocin receptors. These findings support the suggestion that endogenous oxytocin action within the VTA suppresses sucrose intake. We conclude that oxytocin receptors in the VTA play a physiologic role in the control of sucrose ingestion.

Figure 1

A) Mean +/− SEM 10% sucrose intake during the 30-min test session after intra-VTA injection of vehicle or OT. B) Mean +/− SEM water intake during 30-min test sessions after intra-VTA vehicle or OT injection. * p < 0.05 relative to vehicle.

Figure 2

Mean +/− SEM 10% sucrose intake during the 30-min test session after intra-VTA injection of vehicle or OT antagonist. A) Effect of OVT on sucrose intake. B) Effect of L-368,899 on sucrose intake. * p < 0.05 relative to vehicle.

Figure 3

A) Mean +/− SEM 10% sucrose intake during the 30-min test session after intra-VTA injection of vehicle or OT when rats were pre-treated with either vehicle or L-368,899. Significant differences (p < 0.05) across conditions are represented by different letters above the bars. B) Mean +/− SEM percent suppression of sucrose intake by OT after vehicle vs. L-368,899 pre-treatment. * p < 0.05.

Figure 4

A) Representative image of a VTA injection site in a coronal section stained with cresyl violet. B) Diagram of representative VTA injection placements based on the atlas of Paxinos and Watson (2007), showing the VTA region at 4 different anterior-posterior levels relative to bregma.