1. ¹Department of Neuroscience, 'Bernard B. Brodie', University of Cagliari, Cagliari, Italy
2. ²Department of Experimental Biology, University of Cagliari, Cagliari, Italy
3. ³Department of Psychiatry and Human Behavior, University of California, Irvine, CA, USA

Correspondence: Dr M Bortolato, Department of Psychiatry and Human Behavior, 3216, Gillespie Neuroscience Research Facility, University of California, Irvine, CA 92697-4260, USA. Tel: +1 949 824 7080; Fax: +1 949 824 6305; E-mail: bortolam@uci.edu

Received 27 December 2005; Revised 10 April 2006; Accepted 1 May 2006; Published online 14 June 2006.

Abstract

The anticonvulsant topiramate (TPM) has been recently proposed as a novel adjuvant therapy for bipolar disorder and schizophrenia, yet its efficacy remains controversial. As both disorders are characterized by gating deficits, we tested the effects of TPM on the behavioral paradigm of prepulse inhibition (PPI) of the acoustic startle response, a validated animal model of sensorimotor gating. TPM (10, 18, 32, 58, 100 mg/kg, intraperitoneal, i.p.) enhanced PPI in rats in a dose-dependent fashion, prevented the PPI reduction mediated by the dopaminergic agonist apomorphine (0.25 mg/kg, subcutaneous, s.c.) and potentiated the effects of the antipsychotic drugs haloperidol (0.05, 0.1 mg/kg, i.p.) and clozapine (2.5, 5 mg/kg, i.p.). Conversely, TPM elicited no significant effect on the PPI disruption mediated by the NMDA receptor antagonist dizocilpine (0.05, 0.1 mg/kg, s.c.) and surprisingly antagonized the attenuation of dizocilpine-induced PPI disruption mediated by clozapine (5 mg/kg, i.p.). Our results suggest that TPM may exert diverse actions on the neural substrates of sensorimotor gating. While the pharmacological mechanisms of such effects are still elusive, our findings might contribute to shed light on some controversies on the therapeutic action of TPM, and point to this drug as a putative novel adjuvant therapy for some clusters of gating disturbances.