Effect of meta-chlorobenzhydryl urea (m-ClBHU) on benzodiazepine receptor system in rat brain during experimental alcoholism.

Chronic alcohol intake induces neuroadaptive changes in benzodiazepine receptors modulating GABAA receptors that promote alcohol addiction. Analysis of benzodiazepine receptors in the brain of Wistar rats differing by alcohol preference has demonstrated that affinity of [(3)H]flunitrazepam and [(3)H]Ro5-4864 binding with membrane fraction was reduced, while the density of specific binding sites in the brain cortex of heavy drinking and low drinking rats was increased in comparison with rats nonpreferring alcohol. Administration of anticonvulsant meta-chlorobenzhydryl urea increased affinity of benzodiazepine receptors in the brain cortex of heavy drinking rats, which improved GABA neurotransmission in the brain of these animals and reduced alcohol consumption.

[Synaptogenesis and formation of benzodiazepine receptors in the human brain in conditions of prenatal alcoholization].

The aim was to study correlations between the development of synaptic connections and benzodiazepine receptors functionally linked to the brain GABA system in the brain of embryos and 8-15 week fetuses obtained from women with alcoholism. Material from 33 women with alcoholism, stage II (ICD-10 F10.201 and F10.202), and 30 healthy people (controls) was studied. The retardation in the formation of synaptic benzodiazepine receptors and increase in their density was seen in brain cells developing in conditions of prenatal alcoholization compared to controls. The authors consider these findings as a manifestation of compensatory reactions directed towards the adaptation of the fetal nervous system to the action of alcohol and as functional insufficiency of the brain GABA system.

[Platelet peripheral benzodiazepine receptors in alcoholism].

The peripheral-type benzodiazepine receptor (PBR) is an transmembrane protein, distinct pharmacologically, structurally and functionally from the central-type benzodiazepine receptor. The kinetic binding parameters of the specific PBR ligand, the PK11195, have been evaluated in platelets from 36 male alcoholic patients in relation to 19 healthy sex-matched controls. A significant increase of mean value of platelet PBR density was observed in patients as compared to the controls (4733 +/- 379 and 3358 +/- 242 fmol/mg proteins, p < 0.005). There are no statistically significant changes in the receptor affinity values in the group of patients.

[Properties of benzodiazepine receptors of the cerebral cortex of rats with various degrees of ethanol preference]. / Svoistva benzodiazepinovykh retseptorov kory golovnogo mozga krys s raznoi stepen'iu predpochteniia k etanolu.

Comparative study of [3H]-flunitrazepam binding to brain cortex benzodiazepine receptors was performed in rats with different preference to ethanol divided into following groups: 1, rejecting 15% ethanol which was not accessible for 3 months; 2, preferring 15% ethanol freely accessible for 3 months; 3, preferring alcohol and having free access to it except for the last 24 h before decapitation; 4, preferring ethanol not accessible for 3 months. Considerable fall in benzodiazepine receptor affinity was detected in Group 4 as compared to Group 1 (alpha = 0.012; p less than 0.01). The corresponding numbers of [3H]-flunitrazepam binding sites were not different. The data were nonuniform in Groups 2 and 3. Comparison between the two populations substantially different in preferring (Groups 2, 3, 4) and rejecting (Group 1) ethanol reflects the general trend of reduction on the benzodiazepine receptors affinity in preferring rats. This can be a part of biological basis for shaping the craving for alcohol.