Chronic exposure to alcohol during development alters the responses to excitatory amino acids in cultured Purkinje neurons.
The effects of chronic alcohol exposure during development on the responses evoked by glutamate and the selective excitatory amino acid receptor agonists quisqualate (Quis) and kainate were studied in cultured cerebellar Purkinje neurons. The cultures were treated with 22 mM or 44 mM ethanol continuously for one or two weeks during the main period of morphological and physiological development. Extracellular recordings used for most studies characterized the responses to all 3 agonists as initial increase in simple spike firing, usually including a period of burst activity, followed by reduced activity or total inhibition, then return to control firing pattern. Analysis of these responses and background spontaneous activity showed several significant differences between control and ethanol treated Purkinje neurons. Background spontaneous firing, agonist evoked firing, the initial period of activity of the response to Quis, and the inhibitory period of the response to glutamate were all significantly reduced in the chronically treated neurons; the inhibitory period of the response to kainate was significantly increased. In contrast to the effects of chronic ethanol exposure, acutely administered ethanol significantly increased background spontaneous firing and the inhibitory period of the response to Quis. Thus, administering both acute and chronic ethanol altered the responses evoked by excitatory amino acids in the developing Purkinje neurons. The effect of chronic ethanol exposure on some response components was similar for all agonists tested and may be linked to changes in intrinsic membrane properties. However, alterations in the inhibitory component of the agonist responses were agonist specific, indicating that receptor-linked actions of ethanol were involved.(ABSTRACT TRUNCATED AT 250 WORDS)
Gruol
D L
DL
Department of Neuropharmacology, Scripps Research Institute, La Jolla, CA 92037.
D000200:Action Potentials / Q000187:drug effects; D000596:Amino Acids / Q000494:pharmacology*; D000818:Animals; D002478:Cells, Cultured; D002531:Cerebellum / Q000196:embryology; D000431:Ethanol / Q000633:toxicity*; D005971:Glutamates / Q000494:pharmacology; D018698:Glutamic Acid; D007608:Kainic Acid / Q000494:pharmacology; D011689:Purkinje Cells / Q000187:drug effects*; D016318:Quisqualic Acid / Q000494:pharmacology; D051381:Rats; D013997:Time Factors
D000596:Amino Acids; D005971:Glutamates; D000431:Ethanol; D018698:Glutamic Acid; D016318:Quisqualic Acid; D007608:Kainic Acid