Repeated administration of AMPA/kainate antagonists transiently suppresses nicotine-seeking in an operant rat model

This study evaluated the impact of repeated intravenous administration of AMPA/kainate receptor antagonists, NBQX and CNQX, on the operant nicotine self-administration in rats. Wistar rats were subjected to operant intravenous self-administration of nicotine under a fixed ratio 1 schedule of reinforcement. During the maintenance phase of self-administration, 5 mg/kg intravenous NBQX was administered daily prior to the session for a duration of 10 days. Subsequently, the rats underwent a forced abstinence period, remaining in their home cages for two weeks. Following the abstinence, a reinstatement session was conducted. During the final 3 days of abstinence and preceding the reinstatement session, the animals were treated with either NBQX or CNQX (5 and 6 mg/kg intravenously, respectively) to assess their effect on drug-seeking behavior. A ten-day treatment with NBQX did not have any significant influence on the nicotine intake. Repeated administration of NBQX or CNQX before reinstatement had no effect on nicotine-seeking behavior in terms of total numbers of operant responses. However, both of these ligands decreased the number of active nose-pokes (nicotine-seeking) in the first 20 min of the reinstatement session. While no effect of repeated NBQX treatment on nicotine intake was observed, this study reports a transient effect of repeated NBQX or CNQX treatment in the reinstatement of nicotine-seeking behavior in an operant IVSA model. Further pharmacokinetic studies may help optimize behavioral protocols assessing the potential role of AMPA/kainate antagonists in the field of nicotine addiction research where current evidence remains limited.