[³H]Ifenprodil binding in post-mortem brains of Cloninger type 1 and 2 alcoholics: a whole-hemisphere autoradiography study.

The glutamate N-methyl-d-aspartate (NMDA) receptor NR2B subunits are sensitive to ethanol and are found in brain areas related to ethanol addiction, dependence, development of alcohol tolerance, and alcohol withdrawal syndrome. Previous studies indicate that early-onset Cloninger type 2 alcoholics have an intact, responsive, dopaminergic system in the nucleus accumbens (NAC), whereas type 1 alcoholics have dopaminergic defects. NR2B-containing NMDA receptors in the NAC are involved in both non-opioid and opioid receptor-mediated reward. Our aim was to evaluate the putative [(3)H]ifenprodil binding alterations of NR2B receptors in limbic, hippocampal, and cortical brain areas of type 1 alcoholics (n=8), type 2 alcoholics (n=8), and control subjects (n=10) by postmortem whole hemisphere autoradiography. We found significantly different binding levels among these three subject groups, and the main difference was localized in the decreased binding in type 2 alcoholics and controls in the nucleus accumbens. Although preliminary and from relatively small diagnostic groups, these results suggest pathological alterations in the NR2B-mediated reward system of type 2 alcoholics.

Increased metabotropic glutamate 2/3 receptor binding in the perigenual anterior cingulate cortex of Cloninger type 2 alcoholics: a whole-hemisphere autoradiography study.

AIMS: Metabotropic glutamate receptors 2 and 3 (mGluR2/3) contribute to control the level of glutamate in the synapse. In rodents, mGluR2/3 agonists attenuate the reinstatement of alcohol-seeking behavior. Linking possible alterations of the mGluR2/3 system to the etiology and type of alcoholism could provide valuable information for the development of novel mGluR2/3 function modulating therapies in addiction treatment. To date, mGluR2/3 binding density has not been studied in human alcoholics. We aimed to investigate the possible differences in mGluR2/3 binding between Cloninger type 1 anxiety-prone and type 2 impulsive alcoholics and controls. METHODS: We performed a post-mortem whole-hemisphere autoradiography to study the mGluR2/3 binding density of 9 type 1 alcoholics, 8 type 2 alcoholics and 10 controls. [(3)H]LY341495, a potent group II metabotropic glutamate receptor antagonist, was used as the radio-ligand with l-glutamate as a displacer. RESULTS: [(3)H]LY341495 binding density was statistically significantly increased (P = 0.046) in the perigenual anterior cingulate cortex (pACC) of type 2 alcoholics when compared with controls. In other brain areas, no significant difference between the groups was found. CONCLUSION: This preliminary study suggests that impulsive type 2 alcoholics might have alterations in the mGluR2/3 function in the pACC, a brain area presumed to be involved in the control of drug-seeking behaviors and self-control.

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

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.

mGluR1/5 receptor densities in the brains of alcoholic subjects: a whole-hemisphere autoradiography study.

Increased glutamatergic neurotransmission and hyper-excitability during alcoholic withdrawal and abstinence are associated with increased risk for relapse, in addition to compensatory changes in the glutamatergic system during chronic alcohol intake. Type 5 metabotropic glutamate receptor (mGlur5) is abundant in brain regions known to be involved in drug reinforcement, yet very little has been published on mGluR1/5 expression in alcoholics. We evaluated the densities of mGluR1/5 binding in the hippocampus and striatum of post-mortem human brains by using [(3)H]Quisqualic acid as a radioligand in whole hemispheric autoradiography of Cloninger type 1 (n=9) and 2 (n=8) alcoholics and healthy controls (n=10). We observed a 30-40% higher mGluR1/5 binding density in the CA2 area of hippocampus in type 1 alcoholics when compared with either type 2 alcoholics or healthy subjects. Although preliminary, and from a relatively small number of subjects from these diagnostic groups, these results suggest that the mGluR1/5 receptors may be increased in type 1 alcoholics in certain brain areas.

Prevalence of sleep apnea syndrome in lone atrial fibrillation: a case-control study.

BACKGROUND: According to several studies, obstructive sleep apnea predisposes to cardiac arrhythmias, but the prevalence of sleep apnea in specific arrhythmias has not been determined. Our case-control study assesses prevalence of sleep apnea syndrome (SAS) in lone atrial fibrillation (AF). METHODS: Patients with AF (n = 59; 48 men and 11 women; mean age, 59 years; age range, 25 to 84 years) without evident cardiovascular diseases, and their 56 gender-matched, age-matched, and cardiovascular morbidity-matched community control subjects underwent an overnight sleep study. RESULTS: Prevalence of SAS in the AF group was 32%, which did not differ from that in control subjects (29%, p = 0.67). In men, mean neck circumference was higher in the AF group (40.9 cm vs 39.5 cm, p = 0.01) than in control subjects. In men, after adjusting for body mass index and waist circumference, neck circumference was independently related to AF, with an odds ratio (OR) of 1.8 (95% confidence interval, 1.3 to 2.5) per 1-cm increase, and an OR of 5.2 (95% confidence interval, 1.6 to 17.0) for values > 40 cm. Compared to control subjects, the AF group reported more daily/almost-daily tiredness (29% vs 4%, p < 0.001), daily/almost-daily sleepiness (27% vs 7%, p = 0.005), and nightly/almost-nightly breathing pauses during sleep (12% vs 2%, p = 0.03). CONCLUSIONS: SAS seems to be common in lone AF. Nevertheless, we could not show SAS to be more common in patients with AF than in gender-matched, age-matched, and cardiovascular morbidity-matched community control subjects. Compared to control subjects, men with AF seem to have thicker necks, and patients with lone AF report more daytime tiredness, daytime sleepiness, and breathing pauses during sleep.