Involvement of Mouse Cerebellar Neuronal Nitric Oxide Synthase (nNOS) System in the Functional Interaction and Cross-Tolerance between Nicotine and Ethanol
Author(s): M Saeed Dar
Individuals who smoke tobacco overwhelmingly drink alcohol and vice versa. We previously observed functional interaction and cross-tolerance between alcohol and intracerebellar (ICB) nicotine. We now report their mediation by cerebellar nNOS in male CD-1 mice. Nicotine and nNOS inhibitor (nNOSI); N-[(4S)-4-amino-5- [(2-aminoethyl)amino]pentyl]-N -nitroguanidine tris(trifluoroacetate) salt, were directly infused into the cerebellum while ethanol was injected IP. Ethanol (2 g/kg)-induced ataxia (EIA) was potentiated by nNOSI (0.1, 0.5, 1.0 ng) suggesting nNOS-mediation. Pretreatment with nNOSI (0.5, 1.0, 2.0 ng) dose-dependently antagonized nicotine (5 ng)-induced attenuation of EIA suggesting involvement of cerebellar nNOS. When nNOSI (0.5, 1.0, 2.0 ng) and nicotine (5 ng) were microinfused once daily for 5 days, followed 16 h later by ethanol, virtual absence of cross-tolerance was noted. However, when aCSF was infused instead of nNOSI, robust cross-tolerance was noted confirming mediation by cerebellar nNOS system. Overall, these results support role of the cerebellar nNOS in cross-tolerance between ethanol and nicotine.