EFFECT OF NICOTINE ON THE LEVEL OF EXTRACELLULAR AMINO-ACIDS IN THE HIPPOCAMPUS OF RAT

Using microdialysis, we compared intracerebral and subcutaneous admini stration of nicotine for the effect on the levels of extracellular ami no acids in the hippocampus of anesthetized rats. Administration by mi crodialysis of 10 mM nicotine, resulting in a nicotine concentration o f 0.134 mu mol/g in the hippocampus, increased the extracellular level s of aspartic acid, glutamic acid, and serine by 26-60%. At 50 mM nico tine the increases in the levels of aspartic acid, glutamic acid, seri ne, glycine, and glutamine were between 76% and 141%. Subcutaneous adm inistration of nicotine at a dose of 6 mu mol/kg caused a 57% increase in the extracellular level of glutamic acid. After a dose of 12 mu mo l/kg that resulted in a nicotine level of 0.015 mu mol/kg in the hippo campus, the extracellular level of glutamic acid was increased by 100% , and that of aspartic acid by 24%. Thus, higher cerebral nicotine lev els were needed with intracerebral than with subcutaneous administrati on to obtain similar amino acid changes. Prior administration of mecam ylamine or L-kynurenine prevented the subcutaneous nicotine-induced el evation of the extracellular levels of aspartic acid and glutamic acid . Our results indicate that receptor interactions modulate nicotine ef fects and that both nicotinic cholinergic and NMDA/glycine glutamaterg ic receptors participate in the action of nicotine in increasing extra cellular amino acid levels.