Preventing morphine reinforcement with high‐frequency deep brain stimulation of the lateral hypothalamic area

Deep brain stimulation (DBS) has been proposed as a promising intervention for patients with treatment‐refractory substance use disorder. Here, we investigated if high‐frequency DBS in the lateral hypothalamic area (LHA) could affect drug‐induced reinforcement. Rats were bilaterally implanted with bipolar stimulation electrodes in the LHA and trained to the morphine conditioned place preference. DBS (monophasic square pulses, 130 Hz, 100‐microsecond pulse duration and 150 μA) was applied during the morphine‐pairing trials (30 minutes daily for 4 days) or drug‐free postconditioning test (15 minutes) to determine its effect on the acquisition or expression of morphine reward, respectively. LHA DBS during morphine‐conditioning trials blocked subsequent preference for the drug‐associated context. In contrast, DBS in the postconditioning phase failed to inhibit expression of morphine‐induced conditioned place preference. These results were further controlled by ruling out significant changes by DBS in physical performance and anxiety‐like behavior as measured by an open field test and by precluding anhedonia‐like behavior as measured by sucrose consumption test. Our results suggest that LHA DBS can prevent development of morphine reward without diminishing the motivation for naturally rewarding stimuli. Therefore, the LHA could be a potential target for research in the field of DBS‐based treatment of intractable substance use disorder. Further studies will be necessary to assess the translatability of these findings to the clinic. To assess whether high frequency deep brain stimulation (DBS) of the lateral hypothalamic area (LHA) modifies the reinforcing effect of morphine, we stimulated the area (130 Hz, 150 μA, 100 μs) during the morphine‐pairing trials in a conditioned place preference model. We found that LHA DBS during morphine‐conditioning blocked subsequent preference for the drug‐associated context. Yet DBS was effective only in around half of the animals that might be attributable to the fact that we did not fine‐tune stimulation intensity for individual subjects.