Lobeline attenuates methamphetamine-induced stereotypy in adolescent mice

In this study, we investigated the effects of lobeline, an alkaloid constituent of Indian tobacco, on methamphetamine (METH)-induced stereotypy in male ICR mice (41-50 days old), an animal model for amphetamine psychosis. After a single administration of METH (10 mg/kg, i.p.), mice showed an initial short-lasting hyperlocomotion and subsequent stereotyped behaviors with a plateau level 25 min after drug challenge. Pretreatment with lobeline (3.0-30 mg/kg, i.p.) 15 min prior to the drug challenge significantly decreased the intensity of stereotypy and increased its latency to onset in a dose-dependent manner, especially 20 min after the drug challenge. In saline challenge groups, the doses of lobeline examined did not affect spontaneous locomotion nor induced any stereotyped behaviors. High-performance liquid chromatography analysis revealed that the range of lobeline doses examined except 30 mg/kg did not affect apparent monoamine turnover in the cerebral cortex, the region of the striatum and nucleus accumbens, and the region of the thalamus and hypothalamus of the mice 20 and 60 min after the drug challenge. These results suggested that the inhibitory effect of lobeline (3.0-10 mg/kg) on METH-induced stereotypy was not attributed to the change in the apparent monoamine turnover.