Surprising reward downshift activates the lateral habenula, but not the medial habenula, as measured in terms of c-fos expression

Abstract

Convergent results suggest that lateral habenula (LHb) activity reduces reward value and enhances aversive learning. Electrical stimulation of LHb neurons reduces sucrose intake and cocaine/morphine seeking, whereas LHb lesions attenuate taste aversion learning and avoidance of predator odor, retard appetitive extinction, and interfere with appetitive conditioned inhibition training. However, the role of the LHb in consummatory successive negative contrast (cSNC), an animal model of acute anxiety/frustration induced by reward loss, remains unknown. We hypothesized that a surprising reward downshift would enhance activity in the LHb. Three groups of rats received access to sucrose during eleven 5-min sessions. Group 32-2 had access to 32% sucrose for 10 sessions followed by a downshift to 2% sucrose on session 11. Groups 2-2 and 32-32 (unshifted controls) had access to 2% and 32% sucrose, respectively, in each of 11 sessions. After session 11, all animals were perfused and brains were prepared for immunohistochemistry of c-Fos expression, a marker of neuronal depolarization. There was less sucrose consumption on session 11 in Group 32-2 than in Groups 2-2 and 32-32—the cSNC effect (p<0.04). Cell density was elevated in the lateral and medial sections of the LHb in Group 32-2, relative to unshifted groups (ps<0.02). No group differences were observed in the medial habenula (p>0.60). These results suggest that the LHb is involved in the cSNC effect, but its precise function remains to be determined, whether it affects cSNC by detecting the mismatch between obtained and expected rewards (reward relativity) or triggers negative emotion (frustrative nonreward) elicited by the reward loss event. Further studies involving integrated assessment of c-Fos in a wide range of brain regions, including the LHb, may clarify the fit of the LHb activity in the connectome underlying the response to reward downshift.