Proenkephalin-derived peptides act on mu and delta opioid receptors to produce rewarding actions of substances of abuse in several brain regions, including the ventral tegmental area and nucleus accumbens. Specific inbred mouse strains (e.g. DBA/2J and SWR) are characterized by relative insensitivity to drug reward and reinforcement, compared to C57BL/6J. These differences were shown to parallel inter-strain differences in basal proenkephalin expression in the nucleus accumbens (Gieryk et al. 2010).
