Search

An increase in content of acetylcholine (AC) as well as stimulation of choline acetyltransferase and acetylcholinesterase were observed in basal ganglia of rat brain during development of alcohol dependency, thus indicating the activation of the AC structures. Less distinct activation of the AC structures occurred in limbic (frontal) cortex. At the step of complete alcohol dependency the patterns of AC metabolism were considerably normalized in the both brain structures; at the same time, activity of the gamma-aminobutyric acid (GABA) system was decreased, which occurred due to inhibition of the GABA synthesis. At the III step of experimental alcoholism with "physical" dependency on ethanol synthesis and release of the AC were lowered, especially distinct in basal ganglia. These phase alterations in the activity of the AC structures in basal ganglia were accompanied by the similar alterations in content of glutamate: an increase of glutamate at the I step of alcoholism and a decrease--at the III step. Possible mechanisms and pathogenetic role of the phase alterations observed in metabolism of the brain neurotransmitters and in activity of AC- and GABA-structures during development of alcohol dependency are discussed. The data obtained suggest that the specific steps of alcoholism should be taken into consideration in the differential treatment using neurotransmitter drugs.

Neuroleptics (haloperidol) closapine, pimozid, chlorpromazine) diminished the level of free (functionally active) form of acetylcholine (ACh), and, to some extent, the bound form of ACh; they changed the content of the labile-bound (vesicular) form of ACh and weakly influenced the choline-acetyltranspherase activity in the basal ganglia of the rat brain 5 to 30 min after the injection. In contrast to the inhibitory action on the acetyl-cholinesterase (AChE) activity in vitro, most of the neuroleptics, except closapine, increased the AChE activity in vivo. These results indicate that the neuroleptics activate ACh-metabolism and probably stimulate the cholinergic structure in the basal ganglia of the brain; the AChE activity may serve as a criterion of such stimulating action of neuroleptics.