Repeated episodic exposure to ethanol affects neurotrophin content in the forebrain of the mature rat.
Chronic exposure to ethanol can cause deficits in learning and memory. It has been suggested that withdrawal is potentially more damaging than the ethanol exposure per se. Therefore, we explored the effect of repeated episodic exposure to ethanol on key regulators of cortical activity, the neurotrophins. Rats were exposed to ethanol via a liquid diet for 3 days per week for 6-24 weeks. Control rats were pair-fed an isocaloric liquid diet or ad libitum fed chow and water. The concentrations of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophin-3 (NT-3) were determined using enzyme-linked immunosorbant assays (ELISAs). Five telencephalic structures were examined: parietal cortex, entorhinal cortex, hippocampus, the basal nucleus, and the septal nuclei. All five areas expressed each of the three neurotrophins; BDNF was most abundant and NGF the least. The parietal cortex was susceptible to ethanol exposure, NGF and BDNF content increased, and NT-3 content fell, whereas no changes were detectable in the entorhinal cortex. In the hippocampus, the amount all three neurotrophins increased following episodic ethanol exposure. Neurotrophin content in the two segments of the basal forebrain was affected; NGF and NT-3 content in the basal forebrain was reduced and NGF and BDNF content in the septal nuclei was increased by ethanol exposure. In many cases where ethanol had an effect, the change was transient so that by 24 weeks of episodic exposure, no significant changes were evident. Thus, the effects of ethanol are site- and time-dependent. This pattern differs from changes caused by chronic ethanol exposure, hence, neurotrophins must be vulnerable to the effects of withdrawal. Furthermore, the ethanol-induced changes do not appear to fit a model consistent with retrograde regulation, rather they suggest that neurotrophins act through autocrine/paracrine systems.
Department of Neuroscience and Physiology, State University of New York-Upstate Medical University, Syracuse, NY 13210, USA. millermw@upstate.edu
Michael W
MW
Miller
D000818:Animals; D001921:Brain / Q000033:anatomy & histology / Q000187:drug effects / Q000378:metabolism; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D004334:Drug Administration Schedule; D004435:Eating / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D000431:Ethanol / Q000494:pharmacology*; D008297:Male; D009414:Nerve Growth Factors / Q000378:metabolism*; D016548:Prosencephalon / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D020318:Rats, Long-Evans; D013997:Time Factors
D002492:Central Nervous System Depressants; D009414:Nerve Growth Factors; D000431:Ethanol