¹Section of Psychiatry and Behavioral Sciences, Tokyo Medical and Dental University Graduate School, Yushima, Bunkyo-ku, Tokyo, Japan

Correspondence: Dr T Nishikawa, Section of Psychiatry and Behavioral Sciences, Tokyo Medical and Dental University Graduate School, 1-5-45, Yushima, Bunkyo-ku, Tokyo 113-8519, Japan. Tel: +81 3 5803 5237; Fax: +81 3 5803 0135; E-mail: tnis.psyc@tmd.ac.jp

Received 14 November 2005; Revised 5 April 2006; Accepted 19 April 2006; Published online 31 May 2006.

Abstract

To obtain an insight into the development of a new pharmacotherapy that prevents the treatment-resistant relapse of psychostimulant-induced psychosis and schizophrenia, we have investigated in the mouse the effects of selective serotonin reuptake inhibitors (SSRI), fluoxetine (FLX) and paroxetine (PRX), on the established sensitization induced by methamphetamine (MAP), a model of the relapse of these psychoses, because the modifications of the brain serotonergic transmission have been reported to antagonize the sensitization phenomenon. In agreement with previous reports, repeated MAP treatment (1.0 mg/kg a day, subcutaneously (s.c.)) for 10 days induced a long-lasting enhancement of the increasing effects of a challenge dose of MAP (0.24 mg/kg, s.c.) on motor activity on day 12 or 29 of withdrawal. The daily injection of FLX (10 mg/kg, s.c.) or PRX (8 mg/kg, s.c.) from 12 to 16 days of withdrawal of repeated MAP administration markedly attenuated the ability of the MAP pretreatment to augment the motor responses to the challenge dose of the stimulant 13 days after the SSRI injection. The repeated treatment with FLX or PRX alone failed to affect the motor stimulation following the challenge of saline and MAP 13 days later. These results suggest that the intermittent and repetitive elevation of serotonergic tone may inhibit the expression of the motor sensitization induced by pretreatment with MAP. It is proposed that clinically available serotonin reuptake inhibitors could be useful for preventing the recurrence of hallucinatory-paranoid state in drug-induced psychosis and schizophrenia.