EFFECT OF SINGLE AND REPEATED ADMINISTRATION OF GLUTAMATE ANTAGONISTS IN THE DRUG SELF-ADMINISTRATION MODEL
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| Rok publikování | 2022 |
| Druh | Další prezentace na konferencích |
| Citace | |
| Popis | Addiction is a significant health global issue and the options of pharmacological interventions are scarce. Therefore, finding an effective and safe treatment is urgently needed. Recently, a notion of examining the glutamate role on craving reduction seems to be a promising strategy. The aim of our studies was to evaluate the effect of AMPA/kainate receptor antagonists with slightly different mechanism of action on nicotine and methamphetamine intravenous (IV) self-administration in rats. The rats were trained to self-administer the drug for two weeks followed by two weeks of forced abstinence and a drug-free reinstatement session. Single or repeated IV injections of NBQX or CNQX before the session were tested in the second week of maintenance training and the reinstatement session. In the maintenance phase CNQX but not NBQX significantly reduced nicotine intake. Conversely, in the reinstatement, NBQX suppressed nicotine seeking, unlike CNQX. Therefore, we decided to test (sub)chronic effect of NBQX on nicotine intake and we confirmed no effect. Unexpectedly, in this cohort repeated NBQX dosing failed to diminish nicotine seeking in the reinstatement session. NBQX nor CNQX affected methamphetamine intake or reinstatement. Both CNQX and NBQX antagonize glutamatergic AMPA/kainate receptors, but significant pharmacodynamic difference exists between them. CNQX also modulates the glycine site of NMDA receptor. Results may be interpreted as different involvement of individual glutamatergic receptors in various stages of the self-administration dependence model. |
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