Журнал алкоголизма и наркотической зависимости
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Original Anticonvulsant Urea Derivative Alters the Properties of Benzodiazepine Receptors “Central” and “Peripheral” Types in the Cerebral Cortex of “Heavy Drinkers” Rats.

TV Shushpanova, AV Solonskii, NA Bokhan, TP Novozheeva, VV Udut, GA Arbit and VD Filimonov

Objective: studies of anticonvulsants have a stimulating effect on neuronal receptors; in particular GABAA/ benzodiazepine receptor complex (GABAA/BzDR) can be the basis for the development of new approaches to the treatment of alcohol withdrawal syndrome (AWS) and alcohol addiction. Benzodiazepine receptors (BzDRs) of the cerebral cortex of Wistar male rats with a different preference for alcohol and BzDRs in the brain “heavy drinkers” rats, treated with original anticonvulsant meta-chloro-benzhydryl urea (m-ch-BHU) were examined in these study.

Materials and methods: Wistar male rats (n=250) were used in an experimental model of alcoholism. Properties of the BzDRs of the “central” (synaptic) and “peripheral” (mitochondrial) type were examined in membrane fractions obtained from the cerebral cortex of rats under various experimental groups using radio receptor binding assays (RRA) selective ligands: [3H]flunitrazepam and [3H] Ro5-4864 to these receptors respectively.

Results: our study has shown that the binding affinity of [3H] flunitrazepam and [3H] Ro5-4864 with synaptosomal and mitochondrial membranes was decreased, but capacity of receptors was increased in the cerebral cortex of rats prefer alcohol. Administration of m-ch-BHU increased affinity of BzDRs in the cortex of “heavy drinkers” rats that can enhance the mediation of GABA in the brain of these animals.

Conclusion: Our data showed that m-ch-BHU has a stimulating effect on GABAA/BzDRs in the brains of “heavy drinkers” rats and may provide a new pharmacotherapeutic approach to the treatment of alcohol addiction.