The Ghrelin Receptor Antagonist [D-Lys3]-GHRP-6 Reduces the Risk Behavior in the Rat Gambling Model by Altering the Turnover of Dopamine and Serotonin
The effect of the ghrelin receptor antagonist [D-Lys3]-GHRP-6 on the elements of gambling and monoamine metabolism in the rat brain was investigated. For three weeks, the rats were trained in a three-arm maze using the food reinforcement (sunflower seeds). During the first five days, at the end of the 1st arm, the animals received 1 seed, at the end of the 2nd arm, 2 seeds, and at the end of the 3rd arm, 3 seeds. In the following days, the reinforcement was differentiated: each entry in arm 1was reinforced with 1 seed, each second entry in arm 2 was reinforced with 2 seeds and every third entry in arm 3 was reinforced with 3 seeds. Thus, when visiting the 1st arm, the amount of reinforcement was minimal, and the probability of its delivery was maximal. The entry to the 3rd arm was reinforced as much as possible, but with the lowest probability. Rats that had developed a stable conditional locomotion in the maze were injected intranasally with 0.9% NaCl or D-Lys3-GHRP-6 and studied the behavior. 3 days after testing the rats were re-administered with 0.9% NaCl or D-Lys3-GHRP-6. After 80 minutes, the rats were decapitated and the brain structures were isolated. HPLC was used to determine the content of dopamine, serotonin and their metabolites in the hypothalamus, hippocampus, striatum, and olfactory tubercle (the part of ventral striatum). Intranasal administration of the ghrelin receptor antagonist [D-Lys3] -GHRP-6 (20 μL, 1 mg/mL) increased the number of entries into the 1st arm (with a high (100%) probability, but less reinforcement). No significant changes were found in the content of dopamine and serotonin after [D-Lys3]-GHRP-6 administration in the hypothalamus. The serotonin content significantly increased in the left hippocampus. The turnover of monoamines in the olfactory tubercle and striatum changed only in the right hemisphere, while the ratio of the content of 5-hydroxyindoleacetic acid to the content of serotonin increased in both structures. In the right striatum, these changes were also accompanied by an increase in the content of serotonin and dopamine metabolites. Thus, the ability of [D-Lys3]-GHRP-6 to change the strategy of choice in favor of the greatest probability, but the least amount of reinforcement, is based on an increase in the activity of the dopaminergic and serotoninergic systems in the dorsal and ventral striatum of the right hemisphere of the brain and the serotonin content in the hippocampus of the left hemisphere.