1. ¹Psychiatry Program, Neuroscience Research, Novartis Institutes for BioMedical Research, Novartis Pharma AG, Basel, Switzerland
2. ²CNRS UMR 5106, Laboratoire de Neurosciences Cognitives, Université de Bordeaux 1, Avenue des Facultés, 33405 Talence Cedex, France

Correspondence: Dr PH Kelly, Psychiatry Program, Neuroscience Research, Novartis Institutes for BioMedical Research, WSJ-386.262, Novartis Pharma AG, Basel CH-4002, Switzerland. Tel: +41 61 324 4367; Fax: +41 61 324 3811; E-mail: peter.kelly@pharma.novartis.com

Received 18 May 2004; Revised 27 August 2004; Accepted 17 September 2004; Published online 24 November 2004.

Abstract

The habenular nuclear complex is a major influence on brainstem cell groups that influence attention, but its role in attentional performance has not previously been explored. The present study investigated how habenula lesions affect attentional function as assessed by the 5-choice serial reaction time task (5-CSRTT) in male Lister-Hooded rats. Rats were pretrained in the 5-CSRTT before receiving discrete bilateral lesions of the habenula or a sham procedure. In test sessions immediately following recovery from surgery, lesioned rats showed a marked increase in premature responding. Over the course of testing this increase of premature responding declined in magnitude. In contrast, choice accuracy showed no impairment during the earliest postsurgery test sessions but progressively deteriorated over the course of testing. These opposite time courses strongly imply that different mechanisms mediate these two effects of the habenula lesion. Differential effects of drug treatment on these effects further supported this view. Thus, D-amphetamine (0.2 mg/kg s.c.) increased premature responding without affecting choice accuracy. On the other hand, haloperidol (0.01–0.03 mg/kg i.p.) decreased premature responding without significantly affecting choice accuracy. The results are consistent with the view that elevated premature responding in habenula-lesioned animals is mediated by increased dopaminergic activity, whereas impaired choice accuracy is not. Implications of these findings for the hypothesis that habenula dysfunction is involved in cognitive symptoms of schizophrenia are discussed.