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Involvement of sigma 1 receptor in the SSRI-induced suppression of the methamphetamine-induced behavioral sensitization and rewarding effects in mice.

The abuse of methamphetamine causes abnormal behaviors which are indistinguishable from schizophrenia in humans. Recent reports have shown that selective serotonin reuptake inhibitors (SSRIs) have beneficial effects on methamphetamine-related behaviors, including behavioral sensitization and rewarding effects in animals. However, the exact mechanisms by which SSRIs affect methamphetamine-related behaviors are not yet clear. The present study was designed to investigate the effects of SSRIs on the development of methamphetamine-induced behavioral sensitization and rewarding effects in mice. Behavioral sensitization was measured by examining the locomotor activity of mice in a tilting cage after repeated injections of methamphetamine. Repeated administration of methamphetamine significantly induced a behavioral sensitization. Some SSRIs (fluoxetine and fluvoxamine), which have sigma-1 receptor agonistic activity, inhibited the development of methamphetamine-induced behavioral sensitization. Fluoxetine also dose-dependently attenuated the rewarding effects of methamphetamine as measured by the conditioned place preference paradigm. Furthermore, the sigma-1 receptor antagonist NE-100 significantly reversed the inhibitory effects of fluoxetine on methamphetamine-induced behavioral sensitization and rewarding effects. These results suggest that sigma-1 receptor agonistic activity might be involved in the attenuating effects of fluoxetine and fluvoxamine on methamphetamine-induced behavioral sensitization and rewarding effects.