Opioid receptors mediating antinociception from β-endorphin and morphine in the periaqueductal gray

Smith, David J.; Robertson, Brenda S; Monroe, Philip J.; Taylor, David A.; Leedham, Judith A.; Cabral, J.D.Y.

doi:10.1016/0028-3908(92)90010-m

Cited by 33 publications

(15 citation statements)

References 28 publications

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“…A previous study in male rats showed that naloxone methobromide microinjected to the PAG attenuated antinociception induced by a single s.c. dose of morphine [37]. It also has been shown that small doses of various opioid antagonists microinjected to the PAG can attenuate antinociception induced by β-endorphin or morphine microinjected to the PAG [48,54] or amygdala [42] in male rats. The antagonism experiment in the present study confirms that activation of mu opioid receptors in the vPAG plays an important role in antinociception produced by systemic morphine in both male and female rats.…”

Section: Discussionmentioning

confidence: 99%

“…Because there were unequal or inadequate numbers of females in each stage at each dose, the influence of estrous stage on morphine's behavioral effects could not be examined with this dataset. Thus, Experiment 2 was conducted to determine whether the antinociceptive effect of morphine microinjected into the vPAG differs when females are in estrus vs. diestrus-1 phases (the phases we have found to be most different when testing systemic morphine antinociception [48]). F(1,29) =22.41, p<0.001), but these effects were statistically significant only in females that were tested during diestrus-1 (antinociception: p=0.007; immobility: p=0.001).…”

Section: Influence Of Estrous Stage On Behavioral Effects Of Intra-vpmentioning

confidence: 99%

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PAG mu opioid receptor activation underlies sex differences in morphine antinociception

Bernal

Morgan

Craft

2007

Behavioural Brain Research

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Given the findings that (1) systemic opioid antinociception varies by estrous stage in females, and (2) the magnitude of sex differences in opioid antinociception is negatively correlated with opioid agonist efficacy, we hypothesized that sex differences in the function of the descending pain modulatory system are likely influenced by estrous stage in females and by the number of available opioid receptors therein. The present study tested these hypotheses by (1) comparing antinociception produced by morphine microinjection to the ventral periaqueductal gray (vPAG) in females at different stages of the estrous cycle, and (2) examining systemic morphine antinociception in males vs. females under conditions of reduced vPAG mu opioid receptor availability. When estrous stage of females was not controlled for (Experiment 1), there was no significant sex difference in tail withdrawal antinociception following morphine microinjection (0.3-10 μg), although morphine was more potent in males than females in producing immobility. Experiment 2 showed that intra-vPAG morphine produced less antinociception and immobility in estrus than in diestrus females; that is, only estrus females' response to morphine was lower than that of males. Experiment 3 showed that microinjection of the irreversible mu opioid antagonist β-funaltrexamine (β-FNA) into the vPAG shifted the systemic morphine dose-effect curve farther to the right in females than in males. That is, a reduction in available vPAG mu opioid receptors had a greater impact on opioid antinociception in females than in males, suggesting that females have fewer vPAG mu opioid receptors than males. Overall, these data suggest that ovarian hormones and PAG mu opioid receptor density contribute to sex differences in antinociception produced by morphine.

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Section: Discussionmentioning

confidence: 99%

Section: Influence Of Estrous Stage On Behavioral Effects Of Intra-vpmentioning

confidence: 99%

PAG mu opioid receptor activation underlies sex differences in morphine antinociception

Bernal

Morgan

Craft

2007

Behavioural Brain Research

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“…The two opioid drugs in the vlPAG display differential responses to barbiturate anesthesia [79], and are differentially mediated by spinal adrenergic, serotonergic and opioid receptor antagonists [55]. Separate subpopulations of Ì-opioid receptors appear to mediate morphine and ß-endorphin antinociception in the vlPAG given the nonparallel slopes of the dose inhibition curves induced by naltrexone and CTOP [54,80]. Our laboratory [83] found agonist-induced specificity of RVM NMDAinduced mediation of antinociception elicited from the vlPAG in that ß-endorphin antinociception elicited from the vlPAG failed to be altered by either competitive (fig.…”

Section: Opioid Agonists In the Vlpag And Excitatory Amino Acid Antagmentioning

confidence: 99%

“…This antinociceptive interaction persisted when subthreshold doses of ß-endorphin in the amygdala were coadministered with subthreshold doses of morphine in the vlPAG. However, no interaction was observed following coadministration of subthreshold doses of morphine into the amygdala and ß-endorphin into the vlPAG, presumably because ß-endorphin is activating a different neurochemical circuit within the vlPAG than morphine [54,55,[80][81][82][83].…”

Section: Supraspinal Synergy Studies Between Sitesmentioning

confidence: 99%

Supraspinal Circuitry Mediating Opioid Antinociception: Antagonist and Synergy Studies in Multiple Sites

Bodnar¹

2000

J Biomed Sci

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Supraspinal opioid antinociception is mediated by sensitive brain sites capable of supporting this response following microinjection of opioid agonists. These sites include the ventrolateral periaqueductal gray (vIPAG), the rostral ventromedial medulla (RVM), the locus coeruleus and the amygdala. Each of these sites comprise an interconnected anatomical and physiologically relevant system mediating antinociceptive responses through regional interactions. Such interactions have been identified using two pharmacological approaches: (1) the ability of selective antagonists delivered to one site to block antinociception elicited by opioid agonists in a second site, and (2) the presence of synergistic antinociceptive interactions following simultaneous administration of subthreshold doses of opioid agonists into pairs of sites. Thus, the RVM has essential serotonergic, opioid, cholinergic and NMDA synapses that are necessary for the full expression of morphine antinociception elicited from the vIPAG, and the vIPAG has essential opioid synapses that are necessary for the full expression of opioid antinociception elicited from the amygdala. Further, the vIPAG, RVM, locus coeruleus and amygdala interact with each other in synergistically supporting opioid antinociception.

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“…Subsequent work revealed that virtually every tissue that expresses the proopiomelanocortin (POMC) gene converts some or all the ␤-endorphin 1-31 it synthesizes to carboxy-terminal-truncated and amino-terminal-acetylated derivatives (Smith and Funder, 1988). For the most part, these ␤-endorphin 1-31 -derived peptides are biologically inactive, although one, ␤-endorphin 1-27 , displays opioid receptor antagonist activity and blocks ␤-endorphin 1-31 -induced antinociception (Deakin et al, 1980;Nicolas and Li, 1985;Smith et al, 1992;Tseng, 2001). It is not really known why some neurons convert ␤-endorphin 1-31 to opioid-inactive and receptor antagonist derivatives, although POMC serves as the precursor for a number of other peptides, and so it may provide a mechanism for converting POMC neurons from an opioid to a nonopioid phenotype (Raffin-Sanson et al, 2003).…”

mentioning

confidence: 99%

Glycyl-Glutamine, an Endogenous β-Endorphin-Derived Peptide, Inhibits Morphine-Induced Conditioned Place Preference, Tolerance, Dependence, and Withdrawal

Çavun

Göktalay²,

Millington³

2005

J Pharmacol Exp Ther

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Glycyl-glutamine (Gly-Gln; ␤-endorphin [30][31] ) is an endogenous dipeptide synthesized from ␤-endorphin 1-31 . Previous investigations have shown that Gly-Gln inhibits the cardiovascular and respiratory depression caused by morphine and ␤-endorphin 1-31 , but it does not interfere with opioid analgesia. In this study, we tested whether Gly-Gln administration would influence morphine-induced conditioned place preference, tolerance, dependence, or withdrawal. For place preference experiments, rats were conditioned with morphine sulfate (2.5 mg/kg i.p.) or saline on alternate days for 6 days and tested on day 7. Glycyl-glutamine (1-100 nmol i.c.v.) pretreatment inhibited acquisition of a conditioned place preference to morphine significantly. Glycyl-glutamine (100 nmol i.c.v.) also blocked expression of a pre-established morphine place preference, but it did not interfere with acquisition of a conditioned place preference to palatable food, and it did not produce place preference or aversion when given alone to morphine-naive animals. To induce antinociceptive tolerance, rats were treated with morphine (10 mg/kg i.p.) twice daily for 7 days, and morphine antinociception was evaluated with the tail-flick test. Glycylglutamine (100 nmol i.c.v.) pretreatment delayed the onset of morphine tolerance significantly and partially reversed pre-established tolerance. Morphine dependence and withdrawal were assessed by measuring naloxone-precipitated withdrawal symptoms. Glycyl-glutamine inhibited the development of morphine dependence when given to rats twice daily immediately before they received morphine (10 mg/kg i.p.) and suppressed withdrawal symptoms of rats with subcutaneously implanted morphine pellets when administered 5 min before withdrawal was induced with naloxone. Glycyl-glutamine thus attenuates morphine-induced conditioned place preference, tolerance, dependence, and withdrawal without compromising morphine analgesia.

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Opioid receptors mediating antinociception from β-endorphin and morphine in the periaqueductal gray

Cited by 33 publications

References 28 publications

PAG mu opioid receptor activation underlies sex differences in morphine antinociception

PAG mu opioid receptor activation underlies sex differences in morphine antinociception

Supraspinal Circuitry Mediating Opioid Antinociception: Antagonist and Synergy Studies in Multiple Sites

Glycyl-Glutamine, an Endogenous β-Endorphin-Derived Peptide, Inhibits Morphine-Induced Conditioned Place Preference, Tolerance, Dependence, and Withdrawal

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