Recent advances in the understanding of the effects of opioid agents on feeding and appetite

Abstract

The endogenous opioid system has been implicated in a wide range of homeostatic, autonomic and motivational functions, including mediation of food intake. This review examines the roles of the three traditional gene-related opioid peptides (proopiomelanocortin, proenkephalin, prodynorphin) and the three major opioid receptor subtypes and their clones (μ [MOR-1], δ [DOR-1] and κ [KOR-1]) in mediating food intake under spontaneous, deprivation, glucoprivic, stressful and palatable ingestive situations. The opportunities of both the identified selective opioid receptor subtype agonists and antagonists are reviewed with respect to food intake, as well as the problems related to crossed affinities and neuroanatomical mismatches between the major opioid peptides and their presumed receptor subtypes. The cloning of the opioid receptors, together with the recent discoveries of a new generation of opioid peptides (orphanin FQ/nociceptin, endomorphins), are examined for their presumed modulation of food intake. The opportunities created by recent molecular ‘knockdown’ techniques, primarily the use of antisense oligodeoxynucleotides, in creating highly specific and selective probes for elucidating specific receptor mediation of different forms of food intake, are given specific attention. These new data suggest the role of splice variants of opioid receptor clones in differentially mediating different forms of food intake, raising the possibility for the further development of precise pharmaceutical tools with which to address disorders and deficits related to ingestion.

• antisense oligodeoxynucleotides
• 2-deoxy-D-glucose palatability
• DOR-1 clone
• dynorphins
• endogenous opioid peptides
• endomorphins
• β-endorphin
• food deprivation
• genetic obesity
• glucoprivation
• hypothalamic paraventricular nucleus
• KOR-1 clone
• met-enkephalin
• MOR-1 clone
• nociceptin
• nucleus accumbens
• δ opioid receptor
• κ opioid receptor
• μ opioid receptor
• ORL-1/KOR-3 clone
• orphanin FQ
• spontaneous food intake
• stress
• ventral tegmental area