Depressive-like phenotype enhances relapse of nicotine seeking after forced abstinence in rats

Abstract

Objective

Comorbidity of depression and drug addiction is common, but effective treatment is missing. A rat model combining the olfactory bulbectomy (OBX) model and IV drug self-administration has provided evidence of differential reactivity of the OBX rats towards drugs of abuse. This study evaluates nicotine taking and seeking behaviour in this model.

Methods

Adult male Wistar rats were used; in one group, the OBX was performed while the other group was sham-operated. After three weeks of nicotine self-administration (fixed ratio-1 schedule), rats underwent two weeks of forced abstinence followed by a drug-free relapse-like session. Two doses of nicotine were studied: 0.019 and 0.030 mg/kg per infusion. The locomotor test took place before the self-administration protocol and on the first day of abstinence.

Results

OBX induced characteristic hyperactive locomotor phenotype. OBX rats self-administered more nicotine in the experiment using 0.019 mg/kg per infusion, but they reached lower drug intake in the study using 0.030 mg/kg per infusion. However, relapse of nicotine seeking after forced abstinence was significantly higher in the OBX groups in both cohorts.

Conclusion

These results are in line with previous studies showing OBX-induced dissimilarities in drug-seeking and drug-taking and represent complementary information to reports on other substances.

Keywords:

• Abuse
• depression
• nicotine
• olfactory bulbectomy
• self-administration

Acknowledgements

The authors are grateful for the help with the study conducted by Dr. Zuzana Babinska, and for support in behavioral testing and excellent animal care to Jaroslav Nadenicek. The statistical analysis method was kindly suggested and checked for correctness by Dr. Daniela Kuruczova.

Disclosure statement

The authors declare no conflict of interest.

Additional information

Funding

This study was performed at Masaryk University as part of the project ‘Preclinical and clinical research of the Department of Pharmacology in the field of pharmacokinetics, neurobiology of addictions and personalised pharmacotherapy in oncology’ number MUNI/A/1440/2021 with the support of the Specific University Research Grant, as provided by the Ministry of Education, Youth and Sports of the Czech Republic in the year 2022.