Effects of AMPA/kainate antagonists in the various stages of nicotine and methamphetamine self-administration



Rok publikování 2022
Druh Konferenční abstrakty
Popis Addiction is major global problem and the cure for this chronic disease is still limited. Therefore, finding an effective and safe treatment is urgently needed. In recent years, addiction research has focused not only on influencing the dopaminergic pathway of reward, but also on reducing craving by reducing glutamate levels in the brain. The aims of our studies were to evaluate the effect of two different AMPA/kainate receptor antagonists, NBQX and CNQX, on nicotine and methamphetamine intravenous (IV) self-administration in rats. When animals achieved stable intake of the drug, we IV administered a single injection of NBQX or CNQX 10-min before the session to evaluate their effect on drug intake. Subsequently, the rats were kept in their home-cages for two weeks of forced abstinence. This period was followed by a reinstatement session, where the drug was no longer available and NBQX or CNQX was administered to evaluate their effect on drug seeking. In case of NBQX we also assessed its effects on nicotine taking when administered for 10 consecutive days in the same manner. Contrasting effect was brought by NBQX and CNQX in the nicotine dependence studies. In the acute intake phase CNQX but not NBQX significantly reduced drug intake. Conversely, in the reinstatement, NBQX exerted the suppressing effect on nicotine seeking, unlike CNQX. Therefore, we decided to test (sub)chronic effect of NBQX on nicotine intake and we confirmed no effect. NBQX nor CNQX affected methamphetamine intake or reinstatement. NBQX and CNQX are both antagonists of glutamatergic AMPA/kainate receptors but have considerable pharmacodynamic differences. CNQX also modulates the glycine site of NMDA receptor. Our results may be interpreted as different involvement of individual glutamatergic receptors in different phases of the dependence model.

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