Dopamine D1/5 and D2/3 agonists differentially attenuate somatic signs of nicotine withdrawal in rats.

Abrupt tobacco/nicotine cessation after chronic use causes various withdrawal symptoms/signs. There is evidence that dysfunction of brain dopaminergic system might be responsible for some nicotine withdrawal symptoms. The hypothesis for the present study was that different dopaminergic agonists would relieve different nicotine withdrawal signs. Adult male Sprague-Dawley rats were used. (-)-Nicotine bitartrate (9 mg/kg/day, salt content) or equimolar sodium tartrate was infused into each rat via a subcutaneous (s.c.) osmotic minipump for 7 days. To assess nicotine withdrawal signs, several somatic abstinence signs including teeth-chattering/chews, stretches/gasps, ptosis, shakes, and yawns were counted one day after removal of pumps. These signs were attenuated by the s.c. injection of 0.4 mg/kg nicotine bitartrate. Both a dopamine D(1/5) agonist (SKF81297) and a D(2/3) agonist (pramipexole) relieved abstinence signs dose-dependently but differentially. SKF81297 (0.32 mg/kg, s.c.) reduced teeth-chattering/chews but not shakes. Pramipexole (1mg/kg, s.c.) decreased both teeth-chattering/chews and shakes. A low dose of pramipexole (0.1mg/kg, s.c.) significantly increased yawns, consistent with previous studies that the stimulation of D(3) receptors induces yawning. These results indicate that a D(2)-selective agonist should be considered a candidate to relieve nicotine withdrawal symptoms.