L-DOPA attenuates nicotine withdrawal-induced behaviors in rats.

There is some evidence that during nicotine abstinence brain dopamine levels are reduced. The hypothesis for the present study was that the precursor amino acid L-DOPA would relieve nicotine withdrawal-induced behaviors. Separate groups of adult male Sprague-Dawley rats were used. (-)-Nicotine bitartrate (9mg/kg/day, salt content) or equimolar sod ium tartrate was infused into each rat via a subcutaneous osmotic minipump for 7days. To assess nicotine withdrawal behaviors, locomotor activity was measured for 24h in their home cage. Somatic signs were also counted approximately 22h after pump removal. Moreover, depressive-like behaviors were evaluated in the forced swimming test approximately 48h after pump removal. One day after removal of pumps, locomotor activity was suppressed in nicotine-infused rats compared to the tartrate-infused controls. Somatic signs of nicotine withdrawal were increased in nicotine-infused rats compared to the controls. Two days after removal of pumps, increased immobility in the forced swimming test was observed in abstinent nicotine-infused rats as compared with controls. The administration of L-DOPA methyl ester (equivalent to 50mg/kg L-DOPA, s.c.) and benserazide (10mg/kg, s.c.) attenuated somatic signs of withdrawal and reversed nicotine withdrawal-induced depressive-like behaviors in the forced swimming test. It did not mitigate nicotine withdrawal-induced locomotor suppression in the animals' home cages. These results indicate that L-DOPA could be a useful agent to alleviate some nicotine withdrawal symptoms.