Opioids endogenous opioid system

Opioid Systems. Table 2 Endogenous opioid peptides... 

Mayer P, Hollt V Allelic and somatic variations in the endogenous opioid system of humans. Pharmacol Ther 91 167-177, 2001... 

Knapp PE, Maderspach K, Hauser KF (1998) Endogenous opioid system in developing normal and jimpy oligodendrocytes p, and k opioid receptors mediate differential mitogenic and growth responses. Glia 22 189-201... 

Figure 8.2 The endogenous analgesic system. The three major components of the endogenous analgesic system include the periaqueductal gray matter in the midbrain nucleus raphe magnus in the medulla and pain inhibitory complex in the dorsal horns of the spinal cord. This system causes presynaptic inhibition of pain fibers entering the spinal cord. The binding of enkephalin to opioid receptors on the pain fibers prevents release of the neurotransmitter, substance P. As a result, the pain signal is terminated in the spinal cord and does not ascend to higher centers in the CNS.

Spanagel R., Herz A., Shippenberg T. Opposing tonically active endogenous opioid systems modulate the mesolimbic dopaminergic pathway. Proc. Natl. Acad. Sci. U.S.A. 89 2046, 1992. 

Finally, there is an emerging body of evidence to suggest that the endogenous opioid system of the brain may be... 

De Waele, J. P., Audet, R. M., Leong, D. K. and Butterworth, R. F. Portacaval anastomosis induces region-selective alterations of the endogenous opioid system in the rat brain. Hepatology 24 895-901,1996. 

Endogenous opioid systems are an integral part of the reward circuitry 916 PSYCHOMOTOR STIMULANTS 916... 

The body modulates pain through several processes. The endogenous opiate system consists of neurotransmitters (e.g., enkephalins, dynorphins, and /1-endorphins) and receptors (e.g., fl, S, k) that are found throughout the CNS. Endogenous opioids bind to opioid receptors and modulate the transmission of pain impulses. 

Tejedor-Real P, Mico JA, Maldonado R, Roques BP, Gibert-Rahola J. (1995). Implication of endogenous opioid system in the learned helplessness model of depression. Pharmacol Biochem Behav. 52(1) 145-52. 

Nicotinic cholinergic receptors are located on cells that release a wide variety of transmitters (see chapter by Barik and Wonnacott, in this volume), so that nicotine interacts with multiple neurochemical pathways. The roles of cholinergic, dopaminergic, and endogenous opioid systems in physical dependence and withdrawal have been most thoroughly studied and documented. Research on the role of other transmitters and neurochemical mechanisms is rather scattered. Overall, however, research with rodent models of physical dependence has provided a wealth of potential targets for experimental treatments to aid smoking cessation. 

The physiological role of the endogenous opioid system is not limited to pain and analgesia. It unambiguously plays a role in the regulation of the endocrine, behavioral. 

Additionally, an opioid antagonist, naltrexone, has been used to treat children with autism. The results from these studies have been mixed, with some studies showing a mild decrease in hyperactivity and self-injurious behavior, and improved attention (Gillberg, 1995). The children who respond best to this medication appear to have more severe abnormalities in their beta endorphin levels (Bouvard et al., 1995). Overall, the research suggests that the endogenous opioid system, which is important in the reward aspects of affiliation, may also play a role in the neurobiology of autism. 

The part played by endogenous opioid systems in the regulation of these various physiological and behavioral functions has led to the experimental application of opiate antagonists in psychiatric disorders. This chapter focuses on autism and self-injury, which are two potential indications for opiate antagonists in pediatric populations. In adults, treatment with opiate antagonists has shown to be useful in the relapse prevention of alcoholism as part of a comprehensive treatment approach (Anton et ah, 1999, 2001). 

There are two main hypotheses about the involvement of endogenous opioid systems in the maintenance of self-injurious behaviors (Sandman, 1988 Buitelaar, 1993). The pain hypothesis suggests that in some subjects self-injury does not induce pain because excessive basal activity of opioid systems in the CNS has led to an opioid analgesic state. The addiction hypothesis posits that particularly repetitive and stereotyped forms of self-injury stimulate the production and release of en-dogeneous opioids. Therefore, chronic maintenance of self-injury may be due to addiction to endogenous opioids or to positive reinforcement by a central release of opioids triggered by the self-injurious behavior. Irrespective of which hypothesis one favors, treatment with opiate antagonists seems to be a rational approach. 

The biggest challenge is the treatment of addiction itself. Several approaches have been proposed, but all remain experimental. One approach is to pharmacologically reduce cravings. The P-opioid receptor antagonist and partial agonist naltrexone is FDA-approved for this indication in opioid and alcohol addiction. Its effect is modest and may involve a modulation of endogenous opioid systems. 

Spanagel, Rainer, Osborne F. Almeida, Christine Bartl, and Toni S. Shippenberg. 1994. "Endogenous Kappa-Opioid Systems in Opiate Withdrawal Role in Aversion and Accompanying Changes in Mesolimbic Dopamine Release." Psychopharmacology 115 121-27. 

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