Pharmacological blockade of glutamatergic input to the lateral habenula modulates consumption of palatable diet components in male Wistar rats

The lateral habenula (LHb), a small epithalamic nucleus, modifies downstream midbrain dopamine neuron output to regulate negative state and aversion. Furthermore, specific glutamatergic input, from, among others, the lateral hypothalamus and central amygdala to LHb modulates consumption of (palatable) diet components. However, it is currently unclear if blockade of all glutamatergic input to the LHb is sufficient to alter eating behavior.

Here, we used a pharmacological approach to inhibit all glutamatergic input to the LHb by bilateral infusion of either an AMPA/kainate receptor antagonist (CNQX) or an NMDA receptor antagonist (AP5) in the LHb of male Wistars rats. We then measured consumption of various palatable diets a control diet, a free-choice high-fat diet (fcHFD), a free-choice high-sugar diet (fcHSD), and a free-choice high-fat high-sugar diet (fcHFHSD)] at various timepoints up to 24h following infusion. Rats consumed their respective diets for 14 days before infusion of vehicle, CNQX or AP5, performed in counter-balanced random order.

Infusion of CNQX or AP5 did not acutely ( i . e . 1, 3, or 6h following infusion) affect consumption of a fcHFHSD component. Infusion of AP5 decreased fat intake at later time points ( i .e. 10 or 24h following infusion) in fcHFHSD- and fcHFD-fed, but not fcHSD-fed, rats. Combined infusion of CNQX and AP5 decreased sucrose water consumption at 24h following infusion in fcHFHSD-fed rats. Collectively, these observations indicate that blocking glutamatergic transmission in the LHb does not have a major impact on acute consumption of palatable free-choice diet components. Nonetheless, more subtle long-term effects were observed, suggesting a modulatory role of LHb in eating behavior in the current experimental set-up.