m-CF-substituted diphenyl diselenide attenuates all phases of morphine-induced behavioral locomotor sensitization in mice.

BACKGROUND

Behavioral sensitization, thought to underlie some aspects of drug dependence, is typically measured as increased locomotion in response to repeated administration of a drug. The study aimed to investigate the (m-CF3-PhSe) effects on the acquisition, withdrawal, and re-exposure phases of morphine-induced behavioral locomotor sensitization.

METHODS

Swiss male mice were treated with saline or morphine at 10 mg/kg twice a day for 3 days; those of the morphine group were kept in the morphine withdrawal period (5 days). On day 9, mice were re-exposed to morphine. (m-CF3-PhSe) (10 mg/kg) or vehicle was administered at all phases of morphine protocol, and mice performed locomotor activity test. Oxidative stress markers and the levels of opioid, dopamine, and glutamate receptors were determined in samples of the cerebral cortex. (m-CF3-PhSe) administered at all phases of protocol attenuated morphine-induced locomotor sensitization.

RESULTS

Mice exposed to morphine showed reduced weight gain and increased locomotor activity, but (m-CF-PhSe) treatment attenuates the weight gain and behavioral hyperlocomotion effects. (m-CF3-PhSe), independent of the administration phase, modulated the increase of opioidergic (MOR, DOR, KOR) and glutamatergic (NMDA 2A and 2B) protein contents and attenuated redox imbalance in the cerebral cortex of mice exposed to morphine. However, (m-CF3-PhSe) did not modulate cortical protein levels of dopaminergic (D1 and D2) receptors in the acquisition phase of morphine-induced locomotor sensitization protocol.

CONCLUSION

(m-CF-PhSe) was effective against the behavioral and molecular alterations caused by morphine at all phases of locomotor sensitization.