Pharmacological Characterization of Opioid Receptors Influencing the Secretion of Corticotrophin Releasing Factor in the Rat

Buckingham, Julia C.; Cooper, Teresa A.

doi:10.1159/000124618

Cited by 72 publications

(43 citation statements)

References 8 publications

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“…Corticosterone has a permissive effect on diet-induced obesity, and endogenous opioids are involved in the control of hypothalamic-pituitary-adrenal axis activity (23). However, baseline and stress-stimulated corticosterone concentrations did not differ between the two genotypes in this study (Fig.…”

Section: Adult Male Mormentioning

confidence: 53%

Resistance to Diet-Induced Obesity in μ-Opioid Receptor–Deficient Mice

et al. 2005

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Using pharmacological tools, a role for opioid receptors in the regulation of food intake has been documented. However, the involvement of specific receptor subtypes remains questionable, and little information is available regarding a role for opioid receptors in energy metabolism. Using adult male mice lacking the -opioid receptor (MOR) gene (MOR ؊/؊ ), we show that the MOR is not essential for the maintenance of normal levels of ad libitum food intake but does modulate the efficiency of energy storage during high-fat diets through the regulation of energy partitioning. When fed a regular diet, MOR ؊/؊ mice displayed only subtle alterations in energy homeostasis, suggesting a relative overuse of fat as a fuel source in the fed state. When fed a high-fat diet, MOR ؊/؊ mice were resistant to obesity and impaired glucose tolerance, despite having similar energy intake to wild-type mice. This resistance to obesity was associated with a strong induction of the expression of key mitochondrial enzymes involved in fatty acid oxidation within skeletal muscle. This metabolic role of the MOR, which is consistent with the properties of a "thrifty gene," suggests that the MOR pathway is a potential target for pharmacological intervention in the treatment of obesity associated with the intake of fatty diets. Diabetes 54: 3510 -3516, 2005 T he endogenous opioid system encompasses cloned receptor populations (, ␦, and ) and ligands (␤-endorphin, the enkephalins, and the dynorphins). Extensive work indicates that the opioid system plays a role in the regulation of appetite. Opioid receptors and peptides are expressed in sites of the central nervous system that play a role in regulating feeding behavior, and pharmacological experiments using opioid receptor ligands show that agonists promote eating and antagonists decrease food intake, at least in the short term (1-3). Numerous pharmacological studies indicate that opioids also play a role in modulating the rewarding effects of food (3-5). In contrast, little information suggests that opioids have a role in energy metabolism (6 -8).The need to establish the specific role of the opioid receptors in energy homeostasis has led to studies using putative specific opioid receptor ligands or, more recently, antisense probes directed against specific exons of opioid receptor genes (3,9). Pharmacological studies suggest that the and pathways are part of an interconnected brain network and participate in the orexigenic effect of several peptides that regulate food intake (10 -13). However, the interpretation of these data is complicated by our poor knowledge of the in vivo selectivity of ligand-receptor interactions that have been established in vitro (9,14).Recent studies conducted in mutant mice null for the opioid receptors have complemented pharmacological approaches and clarified the role of each receptor in nociception, anxiety, and drug abuse (14). To further define the role of the -opioid receptor (MOR) pathway in energy homeostasis, we characterized mice lacking the MOR gene ...

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Section: Adult Male Mormentioning

confidence: 53%

Resistance to Diet-Induced Obesity in μ-Opioid Receptor–Deficient Mice

et al. 2005

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“…Dynorphin, which plays a role in regulating the stress response, is colocalized with CRF in the paraventricular nucleus of the hypothalamus (Roth et al, 1983) and has been found to modulate the effects of CRF on autonomic function (Overton and Fisher, 1989). Agonists also increase CRF release (Buckingham and Cooper, 1986) and stimulate the hypothalamic-pituitary-adrenal axis (Ur et al, 1997;Laorden et al, 2000). In light of these findings, it seems possible that priming with spiradoline in our study led to downstream activation of brain CRF 1 systems involved in the regulation of stress.…”

Section: Discussionmentioning

confidence: 52%

“…With regard to interactions between opioids and CRF, dynorphin is colocalized with CRF in the hypothalamus (Roth et al, 1983), and administration of agonists can increase CRF release (Buckingham and Cooper, 1986). Agonists stimulate the hypothalamic-pituitary-adrenal axis in rodents (Laorden et al, 2000) and humans (Ur et al, 1997), which is primarily regulated by CRF release in the hypothalamus (Vale et al, 1983).…”

mentioning

confidence: 99%

κ Agonist-Induced Reinstatement of Cocaine Seeking in Squirrel Monkeys: A Role for Opioid and Stress-Related Mechanisms

Valdez

Platt²,

Rowlett³

et al. 2007

J Pharmacol Exp Ther

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Opioid agonists were at one time proposed as candidate pharmacotherapies for cocaine addiction, mainly because of their ability to decrease dopamine neurotransmission and attenuate the behavioral effects of cocaine in laboratory animals. Recent studies, however, suggest that agonists also may mimic and/or enhance some of the effects of cocaine through mechanisms related to stress. The current study used a reinstatement procedure to examine the ability of the agonists spiradoline and enadoline to reinstate extinguished cocaine seeking in squirrel monkeys previously trained to self-administer cocaine under a second-order schedule of i.v. drug injection. Opioid-and stress-related mechanisms were evaluated in antagonism studies with the opioid antagonists naltrexone and nor-binaltorphimine (nor-BNI), the corticotropin-releasing fac- (CP 154,526), and the ␣ 2 -adrenoceptor agonist clonidine combined with either spiradoline or enadoline. When tested alone, priming with spiradoline and enadoline induced significant reinstatement of cocaine-seeking behavior to approximately 45% of the maximum reinstatement induced by cocaine. Reinstatement of cocaine seeking induced by intermediate doses of spiradoline was greater in the presence than in the absence of responsecontingent presentations of a cocaine-paired stimulus. Spiradoline-and enadoline-induced reinstatement of drug seeking was attenuated by naltrexone but not by nor-BNI. Spiradolineinduced reinstatement of cocaine seeking was also antagonized by CP 154,526 and clonidine. The results point to interactions between a subpopulation of opioid receptors and central corticotropin-releasing factor and noradrenergic stress systems in the reinstatement of cocaine seeking induced by agonists.Opioid agonists have been proposed as potential pharmacotherapies for cocaine addiction because of their ability to decrease dopamine neurotransmission (Devine et al., 1993) and suppress certain behavioral effects of cocaine (Mello and Negus, 1998;Schenk et al., 1999;Beardsley et al., 2005). Recent evidence suggests, however, that reductions in cocaine-related behaviors induced by agonists may be secondary to a generalized response-suppressing effect of these drugs, and that the interaction between cocaine and agonists depends on the context and timing of their administration. When tested using a choice procedure of cocaine versus food reinforcement, rhesus monkeys showed an overall decrease in response rate but an increase in cocaine preference after intermittent infusions of the agonist U50,488 (Negus, 2004). McLaughlin et al. (2006a) demonstrated enhancement of cocaine-conditioned place preference when mice were given U50,488 1 h before cocaine and suppression of cocaineconditioned place preference when U50,488 was administered at a later time point.The effects of agonists on cocaine preference may partially reflect activation of physiological stress mechanisms, as opioid receptors and the endogenous opioid peptide dynorphin have been shown to regulate aspects of the stress resp...

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“…The activation results in a sequence of events: enhanced secretion of corticotropinreleasing hormone (CRH) from the parvocellular cells of the nucleus paraventricularis hypothalami (PVN) into the portal vessels of hypophysis, followed by increased adrenocorticotropin (ACTH) production from its precursor proopiomelanocortin (POMC) in the pituitary gland, and elevated synthesis and release of glucocorticoids (in rodents mainly corticosterone, in humans cortisol) into the general circulation from the adrenal gland. Opiate-induced HPA axis changes appear to be mediated centrally, since some agonist stimulated in vitro CRH release from the hypothalamus but not the release of ACTH from the pituitary gland (Buckingham 1982, Buckingham & Cooper 1986b. Chronic administration of morphine may result in tolerance to the stimulatory effect of the opioid on the HPA axis (Buckingham & Cooper 1984, Ignar & Kuhn 1990; the secretion of pituitary ACTH in response to (other) stressors may become suppressed (Briggs & Munsoon 1955, Buckingham & Cooper 1984.…”

Section: Introductionmentioning

confidence: 99%

Congenital vasopressin deficiency and acute and chronic opiate effects on hypothalamo-pituitary–adrenal axis activity in Brattleboro rats

Domokos¹,

Mergl²,

Barna³

et al. 2007

Journal of Endocrinology

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A growing body of evidence suggests that vasopressinergic activity in the hypothalamus is important in stress-related behaviors (like drug abuse) in line with a role in the regulation of the hypothalamo-pituitary-adrenal axis (HPA). We hypothesized that in the naturally vasopressin-deficient Brattleboro rat, acute and chronic morphine treatment may lead to reduced HPA axis activity. Rats were treated either with a single dose of morphine (10 mg/kg subcutaneously) and serial blood samples were taken or were treated twice daily with increasing doses of morphine (10-100 mg/kg subcutaneously) for 16 days and animals were killed by decapitation 4 or 16 h after the last injection. Single morphine injection induced a biphasic ACTH and corticosterone elevation with smaller increases in vasopressin-deficient rats. Chronic morphine treatment induced the typical somatic and HPA axis changes of chronic stress; the absence of vasopressin did not prevent these changes. In rats repeatedly treated with morphine plasma, ACTH and corticosterone levels were elevated both 4 and 16 h after the last injection (short and long withdrawal) and the absence of vasopressin attenuated this response. Our data suggest that vasopressin plays a prominent role in morphine treatment and withdrawalinduced acute hormonal changes, but does not affect development of chronic hyperactivity of the HPA axis.

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Pharmacological Characterization of Opioid Receptors Influencing the Secretion of Corticotrophin Releasing Factor in the Rat

Cited by 72 publications

References 8 publications

Resistance to Diet-Induced Obesity in μ-Opioid Receptor–Deficient Mice

Resistance to Diet-Induced Obesity in μ-Opioid Receptor–Deficient Mice

κ Agonist-Induced Reinstatement of Cocaine Seeking in Squirrel Monkeys: A Role for Opioid and Stress-Related Mechanisms

Congenital vasopressin deficiency and acute and chronic opiate effects on hypothalamo-pituitary–adrenal axis activity in Brattleboro rats

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