Deep Brain Stimulation of the Orbitofrontal Cortex Prevents the Development and Reinstatement of Morphine Place Preference Publisher Pubmed



Fakhriehasl G^{1, 2} ; Sadr SS^{1, 2} ; Karimian SM² ; Riahi E² Show Affiliations
Source: Addiction Biology Published:2020

Abstract

The orbitofrontal cortex (OFC) is involved in compulsive drug seeking and drug relapse. Its involvement in cue-, context-, and stress-induced reinstatement of drug seeking has also been confirmed in animal models. Deep brain stimulation (DBS) was proposed to be an effective intervention for patients with treatment-refractory addiction. Therefore, in the present study, we investigated the potential efficacy of DBS in the OFC for controlling addictive-like behaviors in rats. Rats were bilaterally implanted with electrodes in the OFC and trained to the morphine conditioned place preference (CPP; 3, 5, and 7 mg/kg). High-frequency (HF; 130 Hz) or low-frequency (LF; 13 Hz) DBS-like stimulation was applied during the conditioning (40 minutes, once daily, 3 days) or extinction (20 minutes, once daily, 6-10 days) trials. Following the extinction, morphine preference was reinstated by a priming dose of morphine (2 mg/kg). When applied during the conditioning phase, HF-DBS significantly decreased preference for the morphine-associated context. HF-DBS during the extinction phase of morphine CPP reduced the number of days to full extinction of morphine preference and prevented morphine priming–induced recurrence of morphine preference. LF-DBS did not change any of these addictive behaviors. HF-DBS had no significant effect on novel object recognition memory. In conclusion, HF-DBS of the OFC prevented morphine preference, facilitated extinction of morphine preference, and blocked drug priming–induced reinstatement of morphine seeking. These findings may indicate a potential applicability of DBS in the treatment of relapse to drug use. Further studies will be necessary to assess the translatability of these findings to the clinic. © 2019 Society for the Study of Addiction