Abstract
Endogenous opioids have been implicated in cocaine reward. However, the role of each opioid peptide in this regard is unknown. Notably, the role of each peptide in extinction and reinstatement is not fully characterized. Thus, we assessed whether cocaine-induced conditioned place preference (CPP) and its extinction and reinstatement would be altered in the absence of beta-endorphin. We also examined if sex-related differences would exist in these processes. Male and female mice lacking beta-endorphin and their respective controls were tested for baseline place preference on day 1. On day 2, mice were treated with saline/cocaine (15 mg/kg) and confined to the vehicle- or drug-paired chamber for 30 min, respectively. In the afternoon, mice were treated with the alternate treatment and confined to the opposite chamber. Mice were then tested for CPP on day 3. Mice then received additional conditioning on this day as well as on day 4. Mice were then tested for CPP on day 5. Mice then received extinction training on day 9. On day 10, mice were tested for extinction and then reinstatement of CPP following a priming dose of cocaine (7.5 mg/kg). Male and female mice lacking beta-endorphin did not exhibit CPP following single conditioning with cocaine. On the other hand, only male mice lacking beta-endorphin failed to show CPP after repeated conditioning. Nonetheless, reinstatement of CPP was blunted in both male and female mice lacking beta-endorphin compared to controls. The present results suggest that beta-endorphin plays a functional role in cocaine-induced CPP and its reinstatement, and sex-related differences exist in the regulatory action of beta-endorphin on the acquisition but not reinstatement of cocaine CPP.
Highlights
Cocaine addiction is a serious public health and socioeconomic challenge in the United States and many other countries around the globe
The post hoc test showed a significant difference in the amount of time that wildtype mice spent in the drug-paired chamber (DPCh) vs. vehiclepaired chamber (VPCh) on the postconditioning (D3 or day 5 (D5)) as well as on the reinstatement test day (P < 0.05) but not before conditioning (D1) or the extinction test day (Figure 1, left half of the panel)
These results show that the acquisition of cocaine-induced conditioned place preference (CPP) after single β-Endorphin’s Roles in Cocaine Reward and Reinstatement and repeated conditionings is reduced in the absence of betaendorphin
Summary
Cocaine addiction is a serious public health and socioeconomic challenge in the United States and many other countries around the globe. In 2001, it was estimated that roughly 1.2 million people in the United States consumed cocaine for the very first time (O’Brien and Anthony, 2005). The prevalence of cocaine addiction in Europe and Latin America and other countries including the United States is of a major concern (Castells et al, 2016). Opioid receptor agonists increase the rewarding and reinforcing actions of psychostimulants, which have been demonstrated using self-administration and conditioned place preference (CPP) paradigms (Le Merrer et al, 2009). The role of each opioid peptide in the rewarding and reinforcing action of cocaine is not fully characterized
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