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Chronic ethanol treatment (CET), sufficient for decreasing long-term potentiation (LTP) in rats, also enhances 3H-GABA release from hippocampal slices in these same animals. The mechanism for an increase in GABA release may involve changes in presynaptic receptors. Therefore, we characterized presynaptic autoreceptor modulation of 3H-GABA release in hippocampal slices from control and CET rats. The effects of a GABAB receptor agonist (baclofen) and antagonist [2-hydroxy (OH)-saclofen] were tested for their ability to modulate electrically stimulated 3H-GABA release from superfused hippocampal slices. Baclofen decreased stimulated release in a dose-dependent manner and 2-OH-saclofen increased release consistent with the existence of presynaptic GABAB autoreceptors in hippocampus. The GABAA antagonist bicuculline did not significantly modulate basal or stimulated release. When the effects of baclofen and 2-OH-saclofen were measured in animals 48 hr after withdrawal from CET, presynaptic modulation of release by baclofen and 2-OH-saclofen was decreased. In addition, we examined the density of 3H-baclofen and 3H-bicuculline binding in the hippocampal formation using quantitative autoradiographic techniques. We found that the density of 3H-baclofen binding sites was not affected by CET, whereas the density of 3H-bicuculline binding sites was increased by 28% in ethanol-treated rats. These data may explain how CET increases presynaptic regulation of GABA release from hippocampus that may contribute to the decrease in LTP seen in rats after CET.

Patients with chronic alcoholism and/or Alzheimer's disease suffer from degenerative changes in the cerebral cortex and hippocampus. To investigate possible changes in IGF-1 receptor binding sites in brain tissue of patients with these pathological conditions, the binding of [125I]-IGF-1 was determined in tissues obtained from control, Alzheimer's and/or patients with a history of alcoholism. The four experimental groups examined consisted of patients from similar age groups. Specific binding of [125I]-IGF-1 to cerebral cortical membranes from Alzheimer's patients had significantly more binding sites than age-matched controls, alcoholic patients and alcoholic patients with Alzheimer's disease. Regression analyses indicated that there were no significant differences in [125I]-IGF-1 binding in cerebral cortex with regard to age of patients (1.1% of total variance with a range of 52 to 92 years). Likewise, the time interval between death and autopsy contributed only 1.4% to the total variance in IGF-1 binding. No statistical differences in [125I]-IGF-1 binding were noted in hippocampal tissue from the various patient groups. Thus, human IGF-1 binding sites in cerebral cortex and hippocampus appear to be relatively stable for a number of variables. The increase in cerebral cortical [125I]-IGF-1 binding sites could be due to upregulation of IGF-1 receptors resulting from a decrease in IGF-1 levels in Alzheimer's patients.

A computerized telemetric system using a portable microprocessor receiving unit has been designed for clinical use in ambulatory 24-hour esophageal pH monitoring. The receiving unit can be used with either a pH-sensitive radiotelemetry pill or a standard intraesophageal pH probe. Esophageal pH data is collected under microprocessor control while the patient is in the usual home or work environment. Computerized plotting and analysis of the compiled pH data is performed at the conclusion of the ambulatory testing. The system has been successfully used in patients with symptoms of esophageal reflux and healthy volunteers with no symptoms. The development of a computer-based radiotelemetry system for prolonged monitoring of esophageal pH represents a substantial advance in existing investigational technology. It allows the use of new radiotelemetric techniques of esophageal pH recording with increased patient comfort and acceptance over a 24-hour ambulatory testing period. Microprocessor control of both data collection and analysis allows rapid interpretation of complex 24-hour esophageal pH tracings and greatly facilitates the performance of esophageal pH monitoring as a routine clinical investigation.

The neurotoxic effects of chronic ethanol consumption were investigated in the rat hippocampus by electrophysiological analyses of synaptic function of entorhinal afferents to stratum moleculare of the dentate gyrus. Rats were maintained on ethanol- or sucrose-containing liquid diets for a period of 20 weeks and were withdrawn from the special diets for a period of 8 weeks prior to acute electrophysiological studies. Synaptic response strength (Input/Output (I/O) functions) and synaptic potentiation (paired-pulse, frequency and long-term) were evaluated in each rat. Chronic ethanol treatment failed to influence the response strength or potentiation of basic synaptic responses (EPSP). Rather, the ethanol effects were confined to the population spike (PS). Chronic ethanol treatment produced reductions in PS responses 1) in the asymptotic portions of the I/O curves, 2) in paired-pulse potentiation, 3) in response to 1 and 5 Hz low-frequency stimulation and 4) during the development of long-term potentiation. Expressing PS amplitude as a function of EPSP amplitude emphasized the independence of these actions from those of the synaptic potentials. Definitive evidence concerning the cellular alterations underlying these effects of chronic ethanol treatment are presently lacking. However, available evidence supports the hypothesis that the ethanol-induced decreases in PS responses result from a reduction in the "excitability" of granule cells in the dentate gyrus.

This study investigated the persistent effects of chronic ethanol consumption on the distribution of entorhinal afferents to stratum moleculare of the dentate gyrus. Rats were maintained on ethanol, or sucrose-containing liquid diets, for a period of 20 weeks but were withdrawn from the special diet for at least 8 weeks prior to acute electrophysiologic recordings. One-dimensional laminar analyses were obtained by stepping a microelectrode in 25 microns increments across both the dorsal and ventral blades of the dentate gyrus and sampling the field potentials at each point. Current-source density (CSD) was calculated from the field potential data. Electrical stimulation of the angular bundle elicited a short-latency, negative field potential covering the outer 2/3 of the molecular layer. CSD analysis revealed a major current sink in stratum moleculare bounded by a major current source, localized to the hilus, granule cell layer, and proximal stratum moleculare, and a minor current source localized to the outer molecular layer. Chronic ethanol treatment resulted in (1) a significant shrinkage of the spatial extent of the current sink in stratum moleculare, (2) a significant reduction in the distance from the peak inward synaptic current to the granule cell layer and (3) no change in the distance from the proximal inversion point to the granule cell layer. Taken together, these results indicate a loss of entorhinal afferents in the outer molecular layer. Coupled with available anatomical evidence, these results suggest that chronic ethanol treatment produces a preferential loss of lateral entorhinal afferents to the dentate gyrus.