Nicotine improves probabilistic reward learning in wildtype but not alpha7 nAChR null mutants, yet alpha7 nAChR agonists do not improve probabilistic learning.

摘要: Abstract Cognitive impairments, e.g., reward learning, are present in various psychiatric disorders and warrant treatment. Improving reward-related learning could synergistically enhance psychosocial treatments cognition generally. A critical first step is to understand the mechanisms underlying learning. The dopamine system has been implicated such but less known how indirect activation of this may affect We determined role alpha7 nicotinic acetylcholine receptors (nAChR) on a probabilistic reversal task (PRLT) mice that includes punishment. Male knockout (KO), heterozygous (HT), wildtype (WT) littermate (n = 84) were treated with vehicle, 0.03, or 0.3 mg/kg nicotine. Two cohorts C57BL/6NJ male nAChR ligands, including full agonists PNU282877 AR-R-17779, positive allosteric modulator CCMI, partial agonist SSR180711, antagonist methyllycaconitine. All then tested PRLT. Nicotine (0.3 mg/kg) significantly improved initial WT HT did not improve KO mice, suggesting an involvement pro-learning effects Neither (PNU282987, nor methyllycaconitine) affected mouse PRLT performance however. via mechanism include nAChRs. This improvement unlikely relied solely nAChRs however, since no ligand normal mice. Future assessments other subtypes needed.