The opioid system, consisting of mu, delta, and kappa receptors, is activated by endogenous opioid peptides derived from proopiomelanocortin, proenkephalin, and prodynorphin. These receptors are involved in natural rewarding stimuli and drug abuse, and their activity changes with addiction. This review summarizes current knowledge on how the endogenous opioid system controls hedonic responses and is modified by drugs of abuse in the rodent brain. It covers the anatomy of the opioid system, the effects of local pharmacological manipulation on reinforced behaviors, the consequences of gene knockout on reinforced behaviors and drug dependence, and the effects of chronic drug exposure on opioid system gene expression. Future studies aim to identify key molecular actors and neural sites where opioid peptides and receptors contribute to addictive disorders. The opioid system plays a central role in modulating mood, well-being, and addictive behaviors. It is involved in pain regulation, stress responses, respiration, and endocrine and immune functions. The opioid system is also crucial for modulating reward and addiction. The anatomy of the opioid system in the rodent brain is reviewed, showing the distribution of mu, delta, and kappa receptors, as well as opioid peptide-containing neurons. The opioid system is expressed in the cortex, limbic system, and brainstem, with varying expression levels in different brain regions. The opioid system is involved in food and sexual reinforcement, with studies showing that opioids in the nucleus accumbens (NAc), ventral tegmental area (VTA), and other brain regions modulate these behaviors. The opioid system also plays a role in drug reinforcement, with studies showing that opioids in the VTA and NAc contribute to the reinforcing effects of drugs of abuse. The opioid system is involved in the regulation of drug-seeking behavior and relapse. The review highlights the role of the opioid system in the development and maintenance of addiction, and the potential for targeting opioid receptors in the treatment of addictive disorders.The opioid system, consisting of mu, delta, and kappa receptors, is activated by endogenous opioid peptides derived from proopiomelanocortin, proenkephalin, and prodynorphin. These receptors are involved in natural rewarding stimuli and drug abuse, and their activity changes with addiction. This review summarizes current knowledge on how the endogenous opioid system controls hedonic responses and is modified by drugs of abuse in the rodent brain. It covers the anatomy of the opioid system, the effects of local pharmacological manipulation on reinforced behaviors, the consequences of gene knockout on reinforced behaviors and drug dependence, and the effects of chronic drug exposure on opioid system gene expression. Future studies aim to identify key molecular actors and neural sites where opioid peptides and receptors contribute to addictive disorders. The opioid system plays a central role in modulating mood, well-being, and addictive behaviors. It is involved in pain regulation, stress responses, respiration, and endocrine and immune functions. The opioid system is also crucial for modulating reward and addiction. The anatomy of the opioid system in the rodent brain is reviewed, showing the distribution of mu, delta, and kappa receptors, as well as opioid peptide-containing neurons. The opioid system is expressed in the cortex, limbic system, and brainstem, with varying expression levels in different brain regions. The opioid system is involved in food and sexual reinforcement, with studies showing that opioids in the nucleus accumbens (NAc), ventral tegmental area (VTA), and other brain regions modulate these behaviors. The opioid system also plays a role in drug reinforcement, with studies showing that opioids in the VTA and NAc contribute to the reinforcing effects of drugs of abuse. The opioid system is involved in the regulation of drug-seeking behavior and relapse. The review highlights the role of the opioid system in the development and maintenance of addiction, and the potential for targeting opioid receptors in the treatment of addictive disorders.