The alpha7 and alpha4beta2 nicotinic acetylcholine receptor (nAchR) subtypes have been shown to be involved in memory. It is also known that losses of frontal cortical nAchRs are correlated to declining memory function in Alzheimer's disease, but the subtype-specific role of frontal cortical nAchRs in memory has not been well characterized. Hence, we sought to understand the role of frontal cortical alpha7 and alpha4beta2 nAchR subtypes in both working and reference memory by observing the effects of subtype specific agonists and antagonists on radial arm maze performance. It was found that alpha7 nAchRs in the frontal cortex are involved in working and reference memory, while alpha4beta2 nAchRs are only involved in working memory. Throughout the study, drug treatments did not affect motor functionality in the animals. Our data thus sheds further light on the frontal cortex as an important anatomical locus for nAchR-mediated memory function in the brain, and highlights the differing role of alpha7 and alpha4beta2 nAchRs in long and short term memory.