There is a growing awareness that emotion, motivation, and reward values are important determinants of our behavior. The habenula is uniquely positioned both anatomically and functionally to participate in the circuit mediating some forms of emotive decision making. In the last few years there has been a surge of interest in this structure, especially the lateral habenula (LHb). The new studies suggest that the LHb plays a pivotal role in controlling motor and cognitive behaviors by influencing the activity of dopamine and serotonin neurons. Further, dysfunctions of the LHb have also been implicated in psychiatric disorders, such as depression, schizophrenia, and druginduced psychosis.

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Cognitive impairment is a prominent feature of schizophrenia. Currently there is no well-accepted explanation of the aetiology of this disorder, but recent evidence indicates that dysfunction of the habenula may be involved. We therefore examined whether habenula lesions in Sprague-Dawley rats cause behavioural changes resembling those of schizophrenia. Rats received either habenula lesions, a sham operation or a small lesion of the overlying dorsal hippocampus as a check that effects observed were not due to incidental damage to this structure. As there are alterations of social behaviour, sensorimotor gating and cognition in schizophrenia, we examined comparable behaviours. Social interaction time was measured during a 5-min encounter with a novel juvenile conspecific. Prepulse inhibition of an acoustic startle response, as an index of sensorimotor gating, was measured with prepulses of various amplitudes, and spatial cognitive performance was assessed in the Morris water maze task. Histological analysis showed that habenula lesions substantially damaged both medial and lateral habenula bilaterally while largely sparing neighbouring structures. Assay of choline acetyltransferase (ChAT) in the interpeduncular nucleus terminal region of the habenulo-interpeduncular tract, showed marked reduction (by 80%) in habenula-lesioned animals. Habenula-lesioned rats, but not the control group with small dorsal hippocampus lesions, showed marked impairment of Morris maze performance compared to the sham-operated control group. Social interaction time and prepulse inhibition were not significantly altered in either lesion group. The results are consistent with a role of the habenula in cognition, and with the view that pathology of the habenula may contribute to the cognitive impairments of schizophrenia.