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Chapter 18. Neurobiology of Opiates and Opioids

Mary Jeanne Kreek, M.D.
DOI: 10.1176/appi.books.9781585623440.350941

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The neurobiology of the endogenous opioid system, as well as related neurobiology of opiate addiction, the treatment of addiction, and the management of pain, covers an area of scientific research that has been unfolding over the past 40 years, with increased clinical and laboratory-based information. Between 1992 and 1994, researchers had clearly defined three types of opioid receptors (, , and ) using selective chemical ligands. The challenge to clone the receptor genes was not met until late 1992, at which time two groups working independently in Los Angeles, California, and Strasbourg, France (respectively, the groups of Evans and Kieffer), first cloned an opioid receptor from a neuronal cell line known to have opioid receptor activity. Soon thereafter, the genes were cloned for the specific and opioid receptors, first in rodents, then in humans. Especially rapid advances have been made since the first successful cloning of the genes of the endogenous opioid receptors in late 1992 (e.g., Chen et al. 1993a, 1993b; Evans et al. 1992; Kieffer et al. 1992; J. B. Wang et al. 1993) and many laboratories have written extensive scientific papers on both the early and more recent advances, along with pertinent review articles (Kreek 1986, 1987, 1992, 1996a, 1996b, 1996c, 1996d, 2000a, 2000b, 2001, 2002, 2003, 2005; Kreek and Koob 1998; Kreek et al. 2002, 2004a, 2004b, 2005a, 2005b; LaForge et al. 2000; Novick et al. 1991). There are also many exciting review articles from 2001 onward that may be used to identify more specific scientific papers on the neurobiology of the opioids (Borgland 2001; Contet et al. 2004; Corbett et al. 2006; Cox and Crowder 2004; Evans 2004; Johnson et al. 2005; Kieffer and Evans 2002; Kieffer and Gaveriaux-Ruff 2002; Law et al. 2004; Maher et al. 2005; Nestler 2004, 2005; Ossipov et al. 2005; Pan 2005; Pasternak 2001; Qui et al. 2003; Raehal and Bohn 2005; Snyder 2004; Williams et al. 2001; Zadina 2002).

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FIGURE 18–1. and opioid receptors in stress-related normal physiology.Note. ACTH = adrenocorticotropic hormone; CRF = corticotropin-releasing factor; POMC = pro-opiomelanocortin.Source. Adapted from Kreek et al. 2002.
Table Reference Number
TABLE 18–1. Endogenous opioids and their receptors
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TABLE 18–2. Role of opioid receptor and related endorphin systems in normal physiological functions
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The components of the endogenous opioid system are fully detailed and their function is described to the state of our current knowledge.

Tolerance, physical dependence, and addiction are separate and dissociable phenomena.

Stress and the responsivity to stress play a significant role in each of the major addictions.

Genetics contributes to the vulnerability to develop specific addictions, and functional variants of genes have been documented to alter stress responsivity.

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1.
Which of the terms listed below was coined to describe the whole class of endogenous opioid/opiates?
2.
Which of the following endogenous opioids has not had its parent peptide, from which it is derived, identified?
3.
The role of the opioid receptor and related endorphin systems in normal physiological functions has been studied in all of the following areas except
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