Abstract Rationale: Neonatal ventral hippocampal le- sions in rats have been shown to result in behavioral ab- normalities at adulthood thought to simulate some as- pects of positive and cognitive deficits classically ob- served in schizophrenic patients. Objectives: We investi- gated whether such lesions can also induce deficits in re- ward sensitivity that are related to the negative symp- toms of psychotic disorders. Methods: To investigate the effects of neonatal and adult lesions of the ventral hippo- campus on reward-related behaviors we used the condi- tioned place preference (CPP) test and the saccharin con- sumption model. Results: In contrast to adult-lesioned animals, neonatally lesioned rats exhibited a deficit in amphetamine-induced CPP and a significant reduction in saccharin preference. These deficits are unlikely due to lesion-induced motor impairments as both neonatal- and adult-lesioned rats exhibited a similar hyperlocomotor response to amphetamine. Conclusions: Taken together, these results show that neonatal ventral hippocampal le- sions induce a reduction in reward-seeking behaviors in adulthood that mimic some aspects of the negative symptoms (anhedonia) in psychotic patients. Keywords Schizophrenia · Conditioned place preference · Saccharin intake · Neonatal lesion · Ventral hippocampus · Reward Introduction Schizophrenia is one of the most disabling and emotion- ally devastating illnesses of the brain known to man. Schizophrenia is characterized by a constellation of dis- tinctive symptoms. Relevant animal models of schizo- phrenia must be developed to better understand schizo- phrenia and to develop effective pharmacotherapies against this illness. The most common models rely on the use of psychotogenic substances to produce schizo- phrenic-like symptoms in animals. Recently new non- pharmacological models have emerged based on the neu- rodevelopmental hypothesis of schizophrenia, which suggests that the disorder has its origin in an abnormality of brain development (Duncan et al. 1999; Weinberger 1986). Among these new models long-term consequenc- es induced by neonatal ventral hippocampal lesions in the rat have been proposed by Lipska and coworkers (Lipska and Weinberger 1993, 2000; Lipska et al. 1993) as offering a valid simulation of psychotic disorders. In- deed, neonatal ventral hippocampal lesions in rats have been shown to induce behavioral abnormalities thought to simulate some aspects of positive symptoms and cog- nitive deficits classically observed in schizophrenic patients (Al-Amin et al. 2000; Chambers et al. 1996; Le Pen et al. 2000; Lipska et al. 1993, 1995a 1995b). In addition, neonatal lesioned rats exhibit a postpubertal emergence of abnormal behaviors such as hyperrespon- siveness to stress, novelty, dopamine agonists, and gluta- mate antagonists (Al-Amin et al. 2000; Black et al. 1998; Lipska et al. 1993, 1995a). These postpubertal anomalies are reminiscent of the classically described postpubertal onset of psychotic symptoms in schizophrenic patients. Indeed, the onset of schizophrenia is frequently triggered by a stressful event (Duncan et al. 1999), and psycho- logical stress (Duncan et al. 1999), dopamine agonists (Angrist and Van Kammen 1984; Lieberman et al. 1987), and glutamate antagonists (Meador-Wooddruff et al. 2000) are well documented to precipitate or exacerbate psychotic symptoms in humans. Regarding cognitive processes, neonatal ventral hippocampal lesions induce a postpubertal emergence of deficits in sensorimotor gat- ing (Le Pen et al. 2000; Lipska et al. 1995b) and in spa- tial learning and working memory, as investigated using the radial-arm maze model (Chambers et al. 1996). More recently we have extended these results by showing le- sion-induced deficits in spatial and associative learning using avoidance tasks and the Morris water maze proce- dure (Le Pen et al. 2000). G. Le Pen · L. Gaudet · P. Mortas · R. Mory · J.-L. Moreau ( ✉ ) Pharma Division, Preclinical CNS Research, F-Hoffmann-La Roche Ltd, 4070 Basel, Switzerland e-mail: jean-luc.moreau@roche.com Tel.: +41-61-6886951, Fax: +41-61-6881895 Psychopharmacology (2002) 161:434–441 DOI 10.1007/s00213-002-1092-4 ORIGINAL INVESTIGATION Gwenaëlle Le Pen · Laurent Gaudet · Patrick Mortas Roland Mory · Jean-Luc Moreau Deficits in reward sensitivity in a neurodevelopmental rat model of schizophrenia Received: 25 November 2001 / Accepted: 2 March 2002 / Published online: 20 April 2002 © Springer-Verlag 2002