Abstract
Opioid peptides and receptors are broadly expressed throughout peripheral and central nervous systems and have been the subject of intense long-term investigations. Such studies indicate that some endogenous neuropeptides, called anti-opioids, participate in a homeostatic system that tends to reduce the effects of endogenous and exogenous opioids. Anti-opioid properties have been attributed to various peptides, including melanocyte inhibiting factor (MIF)-related peptides, cholecystokinin (CCK), nociceptin/orphanin FQ (N/OFQ), and neuropeptide FF (NPFF). These peptides counteract some of the acute effects of opioids, and therefore, they are involved in the development of opioid tolerance and addiction. In this work, the anti-opioid profile of endogenous peptides was described, mainly taking into account their inhibitory influence on opioid-induced effects. However, the anti-opioid peptides demonstrated complex properties and could show opioid-like as well as anti-opioid effects. The aim of this review is to detail the phenomenon of crosstalk taking place between opioid and anti-opioid systems at the in vivo pharmacological level and to propose a cellular and molecular basis for these interactions. A better knowledge of these mechanisms has potential therapeutic interest for the control of opioid functions, notably for alleviating pain and/or for the treatment of opioid abuse.
Highlights
The discovery of the endogenous opioid system in the 1970s initiated a new understanding of the mechanisms involved in the activity of both extracted and synthetic opium compounds
Opioid receptors are located in areas involved in the following: (1) pain transmission, such as the thalamus, rostroventral medulla, periaqueductal grey area, pons, or in the spinal cord of the dorsal horn; (2) the rewarding system, such as the nucleus accumbens (NAc), ventral tegmental area (VTA), or the prefrontal cortex; (3) other brain areas, such as the hypothalamus, amygdala, ventral pallidum, globus pallidus, nucleus raphe, hippocampus, and olfactory bulb [4]
The endogenous opioid system is central to addiction
Summary
The discovery of the endogenous opioid system in the 1970s initiated a new understanding of the mechanisms involved in the activity of both extracted and synthetic opium compounds. Opioid receptors are located in areas involved in the following: (1) pain transmission, such as the thalamus, rostroventral medulla, periaqueductal grey area, pons, or in the spinal cord of the dorsal horn; (2) the rewarding system, such as the nucleus accumbens (NAc), ventral tegmental area (VTA), or the prefrontal cortex; (3) other brain areas, such as the hypothalamus, amygdala, ventral pallidum, globus pallidus, nucleus raphe, hippocampus, and olfactory bulb [4] They are presented in peripheral tissues, for example, in the gastrointestinal and respiratory tract [4,5]. The first demonstration of peptide with an anti-opioid activity in 1979 and prediction of the existence of other endogenous anti-opioid peptides in the central nervous system have prompted extensive research This group includes melanocyte inhibiting factor (MIF)-related peptides, cholecystokinin (CCK), nociceptin/orphanin (N/OFQ), neuropeptide FF (NPFF), and several others
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