NBQX attenuates relapse of nicotine seeking but not nicotine and methamphetamine self-administration in rats

Abstract

Objective

Pharmacological manipulations of glutamatergic ionotropic receptors have been suggested as a promising target for addiction treatment. Antagonists of AMPA/kainate receptors were shown to reduce alcohol intake or alcohol-seeking in various animal models. In this study, we evaluated the effect of NBQX, an AMPA/kainate receptor antagonist, on methamphetamine (METH) and nicotine self-administration in rats.

Methods

Male Wistar rats were trained to self-administer METH (0.08 mg/kg per infusion, session of 90 min) and nicotine (0.03 mg/kg per infusion, session of 60 min) under the fixed ratio 1 schedule of reinforcement. The maintenance training was 2 weeks. During the second week, NBQX was injected subcutaneously at doses of 5 or 10 mg/kg 20 min before the session or intravenously (IV) at doses of 1 and 5 mg/kg 10 min before the session. Following the maintenance training, rats were subjected to forced abstinence for 2 weeks and 1 day of the drug-free relapse-like session with IV NBQX treatment performed as before.

Results

Although NBQX did not affect nicotine maintenance, it significantly suppressed the drug-paired responding in the relapse session. Regarding METH, NBQX did not exert a significant effect at either phase of the study.

Conclusions

These findings suggest selective involvement of AMPA/kainate receptors in the relapse of nicotine seeking after a period of forced abstinence.

Keywords:

• AMPA/kainate receptor
• nicotine
• methamphetamine
• self-administration
• relapse

Acknowledgements

The authors are grateful to Petra Kamenikova and Marcela Kucirkova for behavioural testing and excellent animal care.

Disclosure statement

None to declare.

Additional information

Funding

This study, in collaboration with investigators at Howard University in Washington, DC (supported by NIH/NIAAA R03AA022479, YT), was performed at Masaryk University as part of the project “Preclinical and clinical student research in the field of pharmacokinetics, neuropsychopharmacology and personalized pharmacotherapy in oncology”, number MUNI/A/1292/2019, and the project “Pharmacological research in the field of pharmacokinetics, neuropsychopharmacology and oncology” number MUNI/A/1249/2020 with the support of the Specific University Research Grant, as provided by the Ministry of Education, Youth and Sports of the Czech Republic (MEYS CR) in the year 2020 and 2021, respectively.