Reward Processing by the Opioid System in the Brain

Abstract

The opioid system consists of three receptors, mu, delta, and kappa, which are activated by endogenous opioid peptides processed from three protein precursors, proopiomelanocortin, proenkephalin, and prodynorphin. Opioid receptors are recruited in response to natural rewarding stimuli and drugs of abuse, and both endogenous opioids and their receptors are modified as addiction develops. Mechanisms whereby aberrant activation and modifications of the opioid system contribute to drug craving and relapse remain to be clarified. This review summarizes our present knowledge on brain sites where the endogenous opioid system controls hedonic responses and is modified in response to drugs of abuse in the rodent brain. We review 1) the latest data on the anatomy of the opioid system, 2) the consequences of local intracerebral pharmacological manipulation of the opioid system on reinforced behaviors, 3) the consequences of gene knockout on reinforced behaviors and drug dependence, and 4) the consequences of chronic exposure to drugs of abuse on expression levels of opioid system genes. Future studies will establish key molecular actors of the system and neural sites where opioid peptides and receptors contribute to the onset of addictive disorders. Combined with data from human and nonhuman primate (not reviewed here), research in this extremely active field has implications both for our understanding of the biology of addiction and for therapeutic interventions to treat the disorder.

Impaired Hippocampus-Dependent and Facilitated Striatum-Dependent Behaviors in Mice Lacking the Delta Opioid Receptor

“…Accordingly, anatomical and pharmacological data show that local delta opioid receptors can modulate hippocampal activity. These receptors are abundantly expressed in the HPC (Le Merrer et al, 2009), primarily in GABAergic interneurons (Rezai et al, 2012;Scherrer et al, 2006;Svoboda et al, 1999), and their pharmacological activation on hippocampal slices was found to disinhibit principal glutamatergic cells via interneuron inhibition (Lupica, 1995). Moreover, enkephalins, among endogenous ligands of delta receptors, are released in the lateral perforant path, where delta receptor activation is required for high frequency-induced LTP (Bramham et al, 1991;Chavkin et al, 1985).…”

“…Delta opioid receptors are expressed in the hippocampus (HPC), dorsal and ventral striatum, amygdala, and prefrontal cortex (Le Merrer et al, 2009;Scherrer et al, 2006), all key brain substrates for memory function (White and McDonald, 2002). Pharmacological data support the notion that stimulating or inactivating delta opioid receptors impacts memory performance, although the exact implication of delta receptor activity remains unclear.…”

High-fat diet alters the dopamine and opioid systems: effects across development

“…10,11 The opioid system has three endogenous ligands, encoded by precursors such as preproenkephalin (PENK), prodynorphin and pro-opiomelanocortin. Similarly, there are three endogenous opioid receptors, delta, kappa and mu.…”

Activation of μ-Opioid Receptors in the Dorsal Striatum is Necessary for Adult Social Attachment in Monogamous Prairie Voles

“…The endogenous opiate system consists of three classes of opioid receptors: m, k, and d; and their endogenous ligands, endorphin, enkephalin, and dynorphin (Le Merrer et al, 2009). The m-opioid receptor (MOR) mediates a wide variety of natural rewards, including hedonic 'liking' of highly palatable food (Pecina and Berridge, 2000).…”