AMPA receptors in post-mortem brains of Cloninger type 1 and 2 alcoholics: A whole-hemisphere autoradiography study

Abstract

Dysfunction of the brain glutamate system has been associated with alcoholism. Ionotropic glutamatergic alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptors (AMPARs) play an important role in both neurotransmission and post-synaptic plasticity. Alterations in AMPAR densities may also play a role in the neurobiological changes associated with alcoholism. In the present study, [(3)H] AMPA binding density was evaluated in the nucleus accumbens (NAc), frontal cortex, anterior cingulate cortex (ACC), dentate gyrus and hippocampus of Cloninger type 1 (n=9) and 2 (n=8) alcoholics, and compared with non-alcoholic control subjects (n=10) by post-mortem whole-hemisphere autoradiography. The [(3)H] AMPA binding density was significantly higher in the ACC of early onset type 2 alcoholics when compared with controls (p=0.011). There was also a significant negative correlation between [(3)H] AMPA binding and previously published results of dopamine transporter (DAT) density in the ACC in these same brain samples (R=-0.95, p=0.001). Although preliminary, and from a relatively small diagnostic group, the present results help to further explain the pathology of alcohol dependence and impulsive behaviour in type 2 alcoholics.

Alteration in AMPA receptor subunit expression and receptor binding among patients with addictive disorders: A systematic review of human postmortem studies

“…To sum, two out of the three studies showed that the expression of AMPA receptors increased in the hippocampus of the patients with AUD, while the other failed to show changes . A decreased receptor binding or expression in this region of the patients with AUD was identified in two of three studies that examined the amygdala, and no change was found for the cocaine and heroin abusers in the other study .…”

“…With respect to the putamen, two studies to target cocaine abusers and patients with AUD showed no change, whereas overexpression of receptors was observed in the study on heroin abusers . In the frontal cortex, there was no difference among both two studies that investigated patients with AUD . As for the cingulate cortex, binding of AMPA receptor was higher in the Cloninger type 2 AUD patients in one study, whereas there was no significant change in the study for the patients with AUD .…”

“…27 To sum, two out of the three studies showed that the expression of AMPA receptors increased in the hippocampus of the patients with AUD, 20,25 while the other failed to show changes. 18 A decreased receptor binding or expression in this region of the patients with AUD was identified in two of three studies that examined the amygdala, 19,24 and no change was found for the cocaine and heroin abusers in the other study. 26 With respect to the putamen, two studies to target cocaine abusers and patients with AUD showed no change, 21,29 whereas overexpression of receptors was observed in the study on heroin abusers.…”

“…mRNA and protein expression of GRIA 2 were decreased in the basolateral amygdala of patients with AUD (n = 10) in the study by Kryger and Wilce . Karkkainen et al classified patients with AUD into type 1 (age of onset >25 years, and susceptibility to anxiety, n = 9) and type 2 (age of onset <25, and impulsive and antisocial behaviors, n = 8), in accordance with Cloninger's criteria. The authors found an increased [ 3 H]AMPA binding in the ACC of the type 2 patients compared with healthy controls, whereas no differences were detected in the other brain regions of interest.…”

“…All of these studies investigated AMPA receptor binding levels, or AMPA receptor subunit transcripts or protein expression; they compared these indices between patients with substance use disorders and healthy controls. Patients with AUD were targeted in eight studies; five studies used the DSM-IV for the diagnosis, [18][19][20][21][22] two studies relied on daily consumption of ethanol, 23,24 and one study did not specify any criteria. 25 The other four studies included patients with heroin and cocaine addiction, where the bases for the diagnosis were an archived history of abuse in two studies 26,27 and death that resulted from overdose for the other two studies.…”