The efforts of the laboratory are directed to understand the neurochemical basis of ethanol and cannabinoid-induced ataxia. The work exclusively involves the study of the role glutamate-nitric oxide- guanylyl cyclase signaling in the ethanol/cannabinoid-induced cerebellar ataxia. Using stereotaxic techniques for direct drug microinfusion in CD-1 mice, the lab is also investigating the modulation of ethanol and Δ9-THC (main psychoactive substance in the cannabis plant)-induced cerebellar ataxia by several receptor mechanisms such as nAChRs, NMDA, CB1, adenosine, A1 & A2A. Recently, strong cross tolerance between cannabinoid and nicotine and between Δ9-THC and nicotine was observed using cerebellar ataxia as the test response. Currently, focus is on the subtypes of the nAChR that actually mediate the functional cross-tolerance and the role of nitric oxide signaling in the functional interaction and cross-tolerance.
Taslim, N., Al-Rejaie, S., and Dar, M.S. (2008). Attenuation of ethanol-induced ataxia by α4β2 nicotinic acetylcholine receptor subtype in mouse cerebellum: a functional interaction. Neuroscience, 157: 204-213.
Dar, M.S. (2007). Co-modulation of acute ethanol-induced motor impairment by mouse cerebellar adenosinergic A1 and GABAA receptor systems. Brain Res. Bull., 71: 287-295.
Smith, A.D. and Dar, M.S. (2007). Behavioral cross-tolerance between repeated intracerebellar nicotince and acute Δ9-tetrahydrocannabinol-induced cerebellar ataxia: role of cerebellar nitric oxide. J. Pharmacol. Exp. Ther., 322: 243-253.
Al-Rejaie, S. and Dar, M.S. (2005). Antagonism of ethanol ataxia by intracerebellar nicotine: possible modulation by mouse cerebellar nitric oxide and cGMP. Brain Res. Bull., 69: 187-196.
Al-rejaie, S. and Dar, M.S. (2005). Possible role of mouse cerebellar nitric oxide in the behavioral interaction between chronic intracerebellar nicotine and acute ethanol administration. Neuroscience, 138: 575-585.
Dar, M.S. and Meng, Z.-H. (2004). Acute ethanol-induced adenosine diphosphate ribosylation regulates the functional activity of rat striatal pertussis toxin-sensitive G proteins. Alcoholism: Clinical and Experimental Res., 28: 1299-1307.