Hydrocodone and Morphine Possess Similar Rewarding Effects and Reduce ERK and CREB Phosphorylation in the Nucleus Accumbens

The number of prescriptions for hydrocodone-containing opioid analgesics has greatly increased over the past decade. This increase has led to an associated enhancement in the non-medical use of hydrocodone products. There is a lack of evidence to determine the extent of the rewarding effects and signal transduction properties of hydrocodone. Therefore, the present study aimed to examine the rewarding properties of hydrocodone (1 and 5 mg/kg) and morphine (1 and 5 mg/kg) using the conditioned place preference paradigm (CPP) in rats. Both hydrocodone and morphine produced a CPP at the 5mg/kg dose, but not the lower 1mg/kg dose, suggesting that both drugs possess similar rewarding properties in the CPP paradigm. Moreover, hydrocodone and morphine equally reduced phosphorylation levels of ERK and CREB proteins in the nucleus accumbens, suggesting that both drugs exert their effects through signal transduction pathways known to be involved in drug reward and reinforcement. These findings suggest that hydrocodone should be viewed as similarly capable of producing rewarding and euphoric properties as morphine.