PubMed · 1461872
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J Oxenbury, M Brady, T Hodgkinson. 1992. An alcohol problem.. https://pubmed.ncbi.nlm.nih.gov/1461872/
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We have shown that alcoholic patients have a lower number of dopamine transporters in the nucleus accumbens, which mediates the rewarding effects of addictive drugs. Thus, certain dopaminergic agents may be beneficial in the treatment of alcohol withdrawal and in the long-term treatment of alcoholism with selective use.
We have utilized a hippocampal brain slice explant system to assess cellular and synaptic mechanisms underlying the expression of alcohol withdrawal hyperexcitability. Previously, we observed a role for NMDA receptors in the expression of electrographic seizures (EGS) observed immediately upon withdrawal from chronic ethanol exposure in this system. One possible cellular mechanism responsible for these prior results involves NMDAR-mediated neurotoxicity, which was assessed in the present study. Explants were exposed to 35 or 75 mM ethanol for 6 or 12 days and incubated with propidium iodide (PI) to label non-viable cells and then imaged digitally. PI labeling was significantly reduced (36% of control levels) following chronic ethanol exposure (75 mM). When tested following ethanol withdrawal, PI labeling remained significantly reduced in the 75 mM exposed group. We next assessed the effect of an NMDA challenge 24 h following withdrawal. The 35 mM and 75 mM ethanol exposed groups displayed significant 6-fold and 13-fold NMDAR-mediated increases in PI labeling respectively; control explants displayed a 3-fold increase. These data suggest that chronic ethanol exposure prior to withdrawal has a minor neuroprotective effect that slightly diminishes within 24 h of ethanol withdrawal. Furthermore, the data indicate that direct NMDAR activation is required for induction of ethanol withdrawal neurotoxicity.
During ethanol withdrawal, dramatic changes in the concentration of many neurotransmitters may be responsible for many of the adverse effects. In the present study, the technique of microdialysis was used to assay the changes in excitatory and inhibitory amino acids after withdrawal from chronic ethanol intoxication. Rats were made physically dependent on ethanol by vapor inhalation for 4 weeks. The basal concentrations of both arginine and GABA were significantly decreased in ethanol-dependent rats, although there were no significant changes in any of the other amino acid basal concentration assayed (i.e.. glutamate and taurine). During the first 12 h after withdrawal from ethanol, only glutamate increased significantly (p < 0.05) at 6 h, and for the duration of the study period of 12 h. To investigate whether either taurine and ethanol interact with amino acids during ethanol withdrawal, two other ethanol-dependent groups were injected with a single intraperitoneal injection of either taurine or ethanol 5 h after commencement of ethanol withdrawal. The IP injection of ethanol (2 g/kg) significantly increased taurine microdialysate content, and although this dose of ethanol was not able to block completely the increase of glutamate release after ethanol withdrawal, a delayed decrease in glutamate content was observed by the end of the period of the study (i.e., 11-12 h). However, IP injection of taurine (45 mg/kg) significantly blocked the increased glutamate release during ethanol withdrawal. This latter finding suggests that taurine may interact with glutamate, possibly by inducing a blockade of glutamate release during ethanol withdrawal.