Developing a method and software for modeling gambling- and risk-associated states in rodents during intracranial self-stimulation

Background: Intracranial self-stimulation is widely used to study reward and addiction mechanisms in laboratory animals. Aim: The work aimed to evaluate the effectiveness of a newly developed and tested hard- and software system for intracranial self-stimulation experiments in rats, providing flexible stimulation modes that simulate gambling and risk-associated conditions observed in humans. Methods: A custom C# (.NET) real-time application was created to control a microcontroller-based stimulator via a USB interface. Male Wistar rats were implanted with electrodes in the ventral tegmental area (VTA) at the following coordinates: AP = –5.0 mm (from bregma); L = –0.9 mm; H = –8.4 mm from the skull surface. The animals were trained to perform self-stimulation in a two-lever Skinner box using a fixed-ratio (FR1-3) schedule at threshold current intensity. After training, one lever was switched to a variable-ratio (VR3-6) schedule with a 15% increase in current intensity. The behavior was assessed once the self-stimulation response had stabilized. Results: The newly developed software provided stable long-term generation of bipolar pulses (1–1000 µA, 100 Hz) with precise time stamping. Depending on stimulation parameters, the animals preferred either the variable-ratio (VR3-6) or fixed-ratio (FR1-3) schedule. A decrease in the probability of reinforcement in the variable-ratio (VR) schedule led to a shift in preference toward the fixed-ratio (FR) lever. A 7-day course of intraperitoneal paroxetine, a selective serotonin reuptake inhibitor, at a dose of 1 mg/kg/day resulted in a shift in the lever-press ratio toward preference for the fixed-ratio (FR1-3) schedule in a single-trial experiment. Conclusion: The developed system allows for effective assessment of rodent states resembling human gambling and risk-taking during the formation of addictive behavior. A course of paroxetine, a selective serotonin reuptake inhibitor, led to a decrease in the frequency of risk-related choices, resembling gambling and risk-taking behavior in humans.