NMDA receptors in frontal cortex and hippocampus of alcohol consumers

Abstract

et al. 1990; Dodd et al. 1992; Freund & Anderson 1996, 1999 Ridge et al. 2008).Our hypothesis is that permanent neuronal damage produced by chronic alcohol consumption is in part due to progressive changes in NMDA receptors, and that these changes might develop before the beginning of clinical manifestations of chronic alcoholism, including dependence, craving and abstinence. Thus, we assessed here the density of NMDA receptors in frontal cortex and hippocampus -brain areas known to be notably affected by chronic alcohol consumption-in a group of 16 alcohol consumers (AC) (16 male, mean age 58±12 years, post-mortem delay 19±8 hours) in comparison to a control group of 16 non-drinkers (14 male and 2 female, mean age 60±12 years, postmortem delay 17±5 hours) using autoradiographic techniques with the specific NMDA-antagonist [ 3 H]MK801. AC subjects included had not suffered any hepatic, neurologic or psychiatric disorders related to alcoholism. They were classified as moderate consumers (40 to 80 g of absolute alcohol daily for at least 10 years) or heavy consumers (more than 80 g of absolute alcohol daily for at least 10 years, enough to develop chronic alcoholic pathology). We also discriminated between AC cases that were abstinent (alcohol withdrawal minimum one week before death) or non-abstinent (last ethanol ingestion less than 12 hours before death). In consequence, it is unlikely that these subjects would undergo a withdrawal situation that could eventually involve acute changes in NMDA receptors (See Supplementary Material for additional information).

Glutamatergic targets for new alcohol medications

“…NMDAR ligand binding in human post-mortem brains is increased in cortical and limbic areas of alcoholics in some (Freund and Anderson 1999), but not other studies (Villegas et al 2011)—perhaps reflecting differences in the extent of alcohol exposure, ante-mortem duration of abstinence, and cumulative effects of alcohol-related neurotoxicity. Abstinent alcoholics have also been shown to have an attenuated response to the perceptual and cognitive effects of the NMDAR antagonist ketamine (Krystal et al 2003).…”

Lipids and Oxidative Stress Associated with Ethanol‐Induced Neurological Damage

“…Recent research showed that oxidation of [13]C-acetate generates specific neurotransmitters, as [13]C-glutamine, glutamate, and GABA levels were higher in chronic ethanol-exposed rats than in controls [ 86 ]. The production of these molecules may be related to the known effects of GABA receptors [ 16 , 17 , 19 , 117 ], although other receptors are also involved in the effects of ethanol, such as dopamine, acetylcholine, and NMDA receptors [ 118 – 120 ] ( Figure 2 ).…”