Interactions between mecamylamine and alcohol in Long-Evans rats: Flash-evoked potentials, body temperature, behavior, and blood alcohol concentration

Mecamylamine, a noncompetitive antagonist of nicotinic acetylcholine receptors, has many potential clinical applications, including treating alcohol dependency. However, little is known about the combined effects of mecamylamine and alcohol on visual system electrophysiology. We examined the separate and combined effects of mecamylamine (4.0 mg/kg, ip) and alcohol (2.0 g/kg, ip) on flash-evoked potentials (FEPs) recorded from the visual cortex (VC) and superior colliculus (SC) of chronically implanted adult male Long-Evans rats. On separate days, either saline or mecamylamine was given 10 min prior to either saline or ethanol. FEPs were recorded 15 and 30 min after the second injection. In the VC, alcohol significantly decreased the amplitudes of components P-23, N-29, N-39, P-89, N-143, and P-237, but increased P-46. N-63 amplitude was not significantly altered. In contrast, mecamylamine increased the amplitude of P-23, P-46, and N-63, but reduced the amplitude of N-29 and P-237. The combination of mecamylamine and alcohol resulted in amplitudes very similar to alcohol alone for components P-23, N-29, N-63, P-89, N-143, and P-237. However, mecamylamine pretreatment reduced the effects of alcohol on components N-39 and P-46. In the SC, FEP component amplitudes were generally decreased by alcohol but not significantly altered by mecamylamine. Mecamylamine pretreatment did not significantly alter the effects of alcohol on SC amplitudes. Latencies of nearly all components in both structures were significantly increased by all drug treatments, with the greatest increase produced by the combination treatment. Hypothermia was also produced by all drug treatments, with the greatest hypothermia (2.25 degrees C) produced by the combination treatment, most likely accounting for much of the drug-induced increase in latencies. All drug treatments reduced movement during FEP testing, but later in an open field alcohol increased ambulation while mecamylamine reduced movement. Separate groups of experimentally naive adult male Holtzman albino and Long-Evans hooded rats were given (ip) either alcohol or mecamylamine plus alcohol. Tail vein samples were taken 30 min later. For both rat strains, blood alcohol concentration in the mecamylamine pretreatment group was significantly less at this time interval by about 50-60 mg/dL, suggesting a mechanism whereby mecamylamine can mitigate some of the acute effects of alcohol (e.g., on VC components N-39 and P-46). (c) 2012 Elsevier Inc. All rights reserved.