Two glutamate receptors, ionotropic, NMDA 3A (GRIN3A), within the nominated linkage peak on 9q21.33-q33,34 and NMDA 2B (GRIN2B), suggested by one GWAS87 and close to a modest linkage peak on 12p13.31-13.32,88 were significantly associated with scores on the Fagerström Test for Nicotine Dependence (FTND).89, 90 More genes in the glutamatergic system, such as GRIN2A, GRIK2, GRM8, and SLC1A2, showed suggestive association with smoking behaviour in the GWAS reported by Vink et al.87 but without significant replication in candidate gene association studies. Accumulating evidence suggests that blockade of glutamatergic transmission attenuates the positive reinforcing and incentive motivational aspects of nicotine, inhibits the reward-enhancing and conditioned rewarding effects of nicotine, and blocks nicotine-seeking behaviour.91 More attention may be paid to this neurotransmitter system in the future.
