Action of ethanol on responses to nicotine from cerebellar Purkinje neurons: relationship to methyllycaconitine (MLA) inhibition of nicotine responses

The effect of ethanol on responses to nicotine from rat cerebellar Purkinje neurons was investigated using extracellular single-unit recording. System ic administration of ethanol initially enhanced the nicotine-induced inhibi tion from 50% of the Purkinje neurons. However, irrespective of whether the re was an initial enhancement, systemic administration of ethanol antagoniz ed the response to nicotine from the majority of Purkinje neurons. When var ying ethanol concentrations were electro-osmotically applied to this neuron al cell type, the responses to nicotine (6/8) were enhanced when a low conc entration of ethanol (40 mM) was in the pipette, whereas the majority of ni cotine responses (10/11) were antagonized when a higher concentration of et hanol (160 mM) was applied to Purkinje neurons. Thus, the concentration of ethanol presented to the neuron seemed to explain the biphasic consequence of systemically administered ethanol on responses to nicotine. In order to determine whether ethanol affected a specific nACh receptor subtype contain ing the alpha-7 subunit, it was initially established that the nicotinic an tagonists, alpha-bungarotoxin (alpha-BTX) and methyllycaconitine (MLA), whi ch are associated with this subunit, had identical actions on responses to nicotine from Purkinje neurons. When MLA was tested against responses to ni cotine from this cell type, MLA antagonized the response to nicotine from 4 5% (9/20) of the neurons tested. In a direct comparison of the action of et hanol to inhibit responses to nicotine with the action of MLA on the same P urkinje neuron, ethanol inhibited responses to nicotine on all neurons sens itive to MLA. However, ethanol also affected nicotine-induced neural change s from some Purkinje neurons not sensitive to MLA antagonism of nicotine. T hese data support the supposition that ethanol affects a nACh receptor subt ype which has an alpha-7 subunit as well as other nACh receptor subtypes wi thout this specific subunit. (C) 1999 Elsevier Science Ltd. All rights rese rved.