Repeated Electrical Stimulation of Reward-Related Brain Regions Affects Cocaine But Not “Natural” Reinforcement

Abstract

Drug addiction is associated with long-lasting neuronal adaptations including alterations in dopamine and glutamate receptors in the brain reward system. Treatment strategies for cocaine addiction and especially the prevention of craving and relapse are limited, and their effectiveness is still questionable. We hypothesized that repeated stimulation of the brain reward system can induce localized neuronal adaptations that may either potentiate or reduce addictive behaviors. The present study was designed to test how repeated interference with the brain reward system using localized electrical stimulation of the medial forebrain bundle at the lateral hypothalamus (LH) or the prefrontal cortex (PFC) affects cocaine addiction-associated behaviors and some of the neuronal adaptations induced by repeated exposure to cocaine. Repeated high-frequency stimulation in either site influenced cocaine, but not sucrose reward-related behaviors. Stimulation of the LH reduced cue-induced seeking behavior, whereas stimulation of the PFC reduced both cocaine-seeking behavior and the motivation for its consumption. The behavioral findings were accompanied by glutamate receptor subtype alterations in the nucleus accumbens and the ventral tegmental area, both key structures of the reward system. It is therefore suggested that repeated electrical stimulation of the PFC can become a novel strategy for treating addiction.

Reducing the desire for cocaine with subthalamic nucleus deep brain stimulation

“…This hypothesis is further supported by our study showing a differential encoding for preferred and less-preferred reward in the STN (25). A recent study has shown that pretest stimulation (i.e., stimulation only before the behavioral test) of the prefrontal cortex diminished cocaine seeking without diminishing sucrose seeking (9), further supporting the idea that the hyperdirect pathway might be critical for the differential influence of STN on various reward-related behavioral responses. Further studies focusing on the specific contribution of the hyperdirect pathway in reward-related behavior are in due course.…”

“…However, it is now largely accepted that interfering with the DA system affects motivation in general. Other surgical targets such as the nucleus accumbens (8) or the cortex (9) have been tested in animals or in opiates addicts (10) with no convincing results so far.…”

Advanced research on deep brain stimulation in treating mental disorders (Review)

“…Studies involving animal models and imaging research are able to further increase understanding regarding the mechanisms and safety of the treatment. Previous studies have reported that there may be a specific ideal target of DBS treatment for habituation (Table III) (53)(54)(55)(56)(57). However, it should be noted that the potential targets are not mutually independent and selection of the ideal target requires more support from clinical and research data due to potentially overlapping mechanisms and functions.…”

Deep brain stimulation: a mechanistic and clinical update

“…Animal studies showed no effect on drugrelated behaviors after stimulation of the dorsal striatum 193 and lateral hypothalamus. 114 Lateral habenula stimulation was effective in controlling drug consumption but also decreased food consumption, which was considered an undesirable side effect. 62,63 Medial prefrontal cortex stimulation also appeared effective in animal studies, but no human cases have been reported.…”