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Effects of isoflurane anesthesia on addictive behaviors in rats

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Abstract

Rationale

Recently, it has been suggested that isoflurane might reduce dopamine release from rat midbrain dopaminergic neurons, the neurobiological substrate implicated in the reinforcing effects of abused drugs and nondrug rewards. However, little is known about effects of isoflurane on neurobehavioral activity associated with chronic exposure to psychoactive substances.

Objective

The present study was designed to investigate the effects of isoflurane on cocaine-reinforced behavior. Using behavioral paradigm in rats, we evaluated the effects of isoflurane on cocaine self-administration under fixed ratio (FR) and progressive ratio (PR) schedules of reinforcement. We also tested the effects of isoflurane on lever responding by nondrug reinforcers (sucrose and food) in drug-naive rats to control for the nonselective effects of isoflurane on cocaine- and nicotine-taking behavior. To further assess the ability of isoflurane to modulate the motivation for taking a drug, we evaluated the effects of isoflurane on nicotine self-administration. Using different groups of rats, the effects of isoflurane on the locomotor activity induced by a single intraperitoneal injection of cocaine (15 mg/kg) were also examined.

Results

Isoflurane significantly suppressed the self-administration of cocaine and nicotine without affecting food consumption. Unlike food-reinforced responding, responding for sucrose reinforcement was decreased by isoflurane. Isoflurane reduced breaking points under a PR schedule of reinforcement in a dose-dependent manner, indicating its efficacy in decreasing the incentive value of cocaine. Isoflurane also attenuated acute cocaine-induced hyperlocomotion.

Conclusions

The results provided evidence that isoflurane decreases cocaine- and nicotine-reinforced responses, while isoflurane effect is not selective for cocaine- and nicotine-maintained responding. These results suggest that isoflurane inhibitions of cocaine- and nicotine-maintenance responses may be related to decreased effects of dopamine, and further investigation will need to elucidate this relationship.

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Funding

This research was supported by a grant (20182MFDS422 and 20182MFDS425) from the Ministry of Food and Drug Safety in 2021 and National Research Foundation of Korea (NRF) grant funded by the Korea government MSIT (No. 2018R1A5A2025272, No.2019R1I1A1A01052581, No. 2020R1A2C1006559).

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Author notes

  1. Seong Shoon Yoon and Bong Hyo Lee have equal contribution in doing the experiments and writing this manuscript.

Authors and Affiliations

  1. Department of Physiology, College of Korean Medicine, Daegu Haany University, 136 Sincheondong-ro, Suseong-gu, Daegu, 42158, Republic of Korea

    Seong Shoon Yoon, Seong Ho Lee, Seon-Ju Jeong & Chae Ha Yang

  2. Department of Acupuncture, Moxibustion and Acupoint, College of Korean Medicine, Daegu Haany University, Daegu, 42158, Republic of Korea

    Bong Hyo Lee

  3. Department of Anatomy and Histology, College of Korean Medicine, Daegu Haany University, Daegu, 42158, Republic of Korea

    Seong Hun Choi

  4. Medical Research Center, College of Korean Medicine, Daegu Haany University, Gyeongsan, 38610, Korea

    Sang Chan Kim

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  1. Seong Shoon Yoon
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Yoon, S.S., Lee, B.H., Lee, S.H. et al. Effects of isoflurane anesthesia on addictive behaviors in rats. Psychopharmacology 239, 3621–3632 (2022). https://doi.org/10.1007/s00213-022-06236-z

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