Reinforcing systems of the brain and quantification of their work

Abstract

Background. The reinforcing systems of the brain are represented mainly by the ventral forbrain dopaminergic bundle, which innervates the emotiogenic structures of the limbic system. Their study comes down to the reproduction of unconditioned (self-stimulation, self-administration) and conditioned reflex (preference for place, temperature, color) reactions. Questions regarding the quantitative assessment of the brain's reinforcing systems remain unresolved. For self-stimulation of brain structures, the change of the pedal presses in the Skinner chamber and some calculated coefficients are used, for example, the “mismatch coefficient,” which characterizes the temporal characteristics of the pedal pressings. The aim of this study was to develop, test and substantiate an additional objective quantitative method for assessing the reinforcing systems of the brain, called the “addiction coefficient” based on an analysis of the effect of three psychoactive compounds (amphetamine, morphine and ethanol) in different doses on self-stimulation of the lateral hypothalamus in rats. Methods. The main method for studying the reinforcing systems of the brain was the reaction of self-stimulation of the lateral hypothalamus in Wistar rats, which was modulated by the administration of psychoactive substances. The psychomotor stimulant amphetamine (phenamine) hydrochloride (0.5; 1; 2; 4 mg/kg), the narcotic analgesic morphine hydrochloride (1; 2; 4; 8 mg/kg) and ethanol (0.5; 1; 2; 4 g/kg), administered intraperitoneally were used as inductors of reinforcing. The control was the administration of different doses of 0.9% NaCl solution (0.1; 0.2; 0.4; 0.8 ml/rat). Results. The use of different controls, characterized by an increase or decrease in the self-stimulation reaction in response to the introduction of a 0.9% NaCl solution, showed that calculated coefficients, such as the “mismatch coefficient,” can also change in different directions and do not objectively reflect the reinforcing effects of pharmacological substances. The “addiction coefficient” we propose, which reflects the component of psychic dependence, always changes unidirectionally towards an increase. The degree of this increase can be tens and hundreds of percent of the control, and is significantly independent of the initial values of self-stimulation. As expected, the “addiction coefficient” increases most clearly after the administration of the psychostimulant amphetamine and less significantly after injections of morphine and ethanol. Conclusion. It is concluded that the “addiction coefficient” of a psychoactive substance, calculated as the ratio of the increase in pedal presses to the value of the “mismatch coefficient,” is a clear quantitative indicator when assessing the reinforcing properties of psychoactive substances in the self-stimulation reaction of the lateral hypothalamus. The “addiction coefficient” does not significantly depend on the initial level of self-stimulation and is recommended for a comparative assessment of the reinforcing properties of primarily related psychoactive compounds.