The selective CCK-B receptor antagonist L-365,260 enhances morphine analgesia and prevents morphine tolerance in the rat

Dourish, C T; O’Neill, Michael F.; Coughlan, J.; Kitchener, Scott; Hawley, D.; Iversen, Susan D.

doi:10.1016/0014-2999(90)90129-t

Cited by 259 publications

(97 citation statements)

References 28 publications

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“…This supports the predominant involvement of CCKB receptors in the mediation of endogenous CCK modulation of opiate antinociception in the rat CNS. However, while much of this information has been obtained in thermal (Dourish et al, 1990;Wiesenfeld-Hallin et al, 1990;Lavigne et al, 1992) and mechanical (Dourish et al, 1990) models of nociception employing an acute, high threshold noxious stimulus in rodents, clinical pain elicited by either tissue/nerve injury or disease is a tonic phenomenon with a persistent, lower intensity that may also have an associated inflammatory component. The present study has now extended the investigation of CCK-opiate interactions to include modulation of morphine antinociception in the formalin model of prolonged rather than acute nociception.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, CCK antagonists have been found in rodents to prevent the development of tolerance (Dourish et al, 1988(Dourish et al, , 1990Kellstein & Mayer, 1991) and/or the re-inforcing properties (Higgins et al, 1992) of morphine suggesting that there may be a tonic modulation of the effect of morphine on dopaminergic transmission by endogenous CCK.…”

Section: Introductionmentioning

confidence: 99%

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Effect of CCK receptor antagonists on the antinociceptive, reinforcing and gut motility properties of morphine

Singh

Oles

Field

et al. 1996

British J Pharmacology

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1 The ability of a selective CCKA receptor antagonist PD 140548 and a selective CCKB receptor antagonist CI-988 (formerly PD 134308) to modulate the various in vivo properties of morphine was investigated in the rat. 2 PD 140548 dose-dependently (0.001 -1.0 mg kg-1, i.p.) antagonised the development of conditioned place preference to morphine (2.0 mg kg'-, s.c.). In contrast, CI-988 (0.01 -1.0 mg kg-', i.p.) did not affect this morphine-induced behaviour. Neither of the CCK receptor antagonists blocked or generalised to the morphine (3.0 mg kg-', i.p.) discriminative stimulus. 3 CI-988 (0.001-10.0 mg kg-', s.c.) at doses of 0.05 and 0.1 mg kg-' (s.c.), potentiated the antinociceptive action of a threshold dose of morphine (5.0 mg kg-', i.p.) in a radiant heat model of acute nociception, the rat tail flick test. Furthermore, at 0.01 mg kg-' it potentiated the antinociceptive action of morphine (3.0 mg kg-') during the acute phase of the rat paw formalin test. And at doses of 0.01 and 0.1 mg kg-' it also potentiated the antinociceptive action of morphine (1.0 mg kg-') during the tonic phase of the formalin test. However, in both models, higher doses of CI-988 were ineffective. In contrast, PD 140548 (0.001 -10 mg kg-', s.c.) was only active at a dose of 1.0 mg kg-1 (s.c.) and only in the tonic phase of the formalin test. Neither CI-988 nor PD 140548 possessed any intrinsic antinociceptive action in either of the tests. Chronic treatment with CI-988 (0.01 mg kg-', s.c.) prevented the development of tolerance to morphine antinociception (4 mg kg-', s.c.) following a 6 day period of twice daily injections of morphine escalating from 1 to 16 mg kg-' (i.p.). 4 Morphine dose-dependently (1-10 mg kg-', s.c.) reduced the distance travelled by a charcoal meal in the rat intestine. Neither PD 140548 (0.01 -1.0 mg kg-', i.p.) nor CI-988 (0.01 -1.0 mg kg-', i.p.) potentiated or suppressed this inhibitory action of morphine. 5 In conclusion, the results of the present study indicate that CCKA and CCKB receptors modulate different properties of morphine. Thus, whilst a selective CCKA receptor antagonist blocked the rewarding properties of morphine, a selective CCKB receptor antagonist potentiated the antinociceptive action. However, neither compound displayed a potential for modulating the influence of morphine on gastro-intestinal motility. It is suggested that these findings may have important implications for development of CCK receptor antagonists as analgesic adjuncts to the therapeutic use of morphine.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Effect of CCK receptor antagonists on the antinociceptive, reinforcing and gut motility properties of morphine

Singh

Oles

Field

et al. 1996

British J Pharmacology

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“…Faris et al (1983) found that CCK reduced the antinociceptive effects produced by the release of endogenous opioids, and did not modify non-opiate responses induced by hind paw foot shock. In addition, numerous studies have shown that peripherally administered CCK antagonists potentiate opioid antinociceptive responses, confirming a functional antagonism of the opioid system by the CCK system (Watkins et al, 1985;Hendrie et al, 1989;Dourish et al, 1990;Wiesenfeld-Hallin et al, 1990;Lavigne et al, 1992) Tt has been hypothesized that CCK down-egulates opioid effects through activation of CCK-b receptors. However, MK329, a selective CCKA antagonist, also potentiated the analgesic effects of opiates (Rattray et al, 1988;Hendrie et al, 1989).…”

Section: Introductionmentioning

confidence: 88%

Modulation of opioid antinociception by CCK at the supraspinal level: evidence of regulatory mechanisms between CCK and enkephalin systems in the control of pain

Noble

Derrien

Roques

1993

British J Pharmacology

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1 Much evidence in the literature supports the idea that cholecystokinin (CCK) interacts with opioids in pain mechanisms. In this work, we have investigated the supraspinal interactions between enkephalins and CCK, using the hot plate test in mice. 2 Intracerebroventricular (i.c.v.) administration of BDNL (a mixed CCKA/CCKB agonist) induced dose-dependent antinociceptive responses on both paw lick and jump responses. In contrast, using the same test, the i.c.v. injection of BC 264 (a selective CCKB agonist) induced a hyperalgesic effect, which was restricted to paw licking and occurred only at a high dose of 2.5 nmol. 3 In addition, i.c.v. administration of BDNL potentiated the antinociceptive effects of the mixed inhibitor of enkephalin degrading enzymes, RB 101 and of the ni-agonist, DAMGO, while BC 264 reduced these effects. 4 Furthermore, at a dose where it interacts selectively with b-opioid receptors, the opioid agonist BUBU reversed the hyperalgesic responses of BC 264 (2.5 nmol) but was unable to modify the effects induced by BDNL. 5 Taken together, these results suggest the existence of regulatory mechanisms between CCK and enkephalin systems in the control of pain. These regulatory loops could enhance the antinociceptive effects of morphine allowing the opiate doses used to be reduced and thus, possibly, the side-effects to be minimized.

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“…On the other hand, i.t. administration of CCK-B receptor antagonists and receptor antisense oligonucleotides enhance morphine antinociception (Dourish et al, 1990;Vanderah et al, 1994). Under normal conditions, endogenous CCK does not appear to influence basal pain sensitivity, as spinal treatment with CCK-B receptor antagonists produces antinociception only in the presence of opioids (Watkins et al, 1985).…”

Section: Introductionmentioning

confidence: 99%

The roles of nerve growth factor and cholecystokinin in the enhancement of morphine analgesia in a rodent model of central nervous system inflammation

et al. 2009

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Animal models of inflammatory pain are characterized by the release of inflammatory mediators such as cytokines and neurotrophic factors, and enhanced analgesic sensitivity to opioids. In this study, we examine the mechanisms underlying this effect, in particular the roles of cholecystokinin (CCK) and nerve growth factor (NGF), in an animal model of central nervous system (CNS) inflammation induced by spinal administration of lipopolysaccharide (LPS). Although spinal administration of LY-225910 (25 ng), a CCK-B antagonist, enhanced morphine analgesia in naïve rats, it was unable to do so in LPS-treated animals. Conversely, spinal CCK-8S administration (1 ng) decreased morphine analgesia in LPS-treated rats, but not in naıve animals. Further, spinal anti-NGF (3 mg) was able to reduce morphine analgesia in LPS-treated rats, but not in naïve animals, an effect that was reversed by spinal administration of LY-225910. While CCK-8S concentration was increased in spinal cord extracts of LPS animals as compared to controls, morphine-induced spinal CCK release in the extracellular space, as measured by in-vivo spinal cord microdialysis was inhibited in LPS animals as compared to controls, and this was reversed by anti-NGF pretreatment. Finally, chronic spinal administration of b-NGF (7 mg/day) for 7 days enhanced spinal morphine analgesia, possibly by mimicking a CNS inflammatory state. We suggest that in intrathecally LPS-treated rats, spinal CCK release is altered resulting in enhanced morphine analgesia, and that this mechanism may be regulated to an important extent by NGF.

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The selective CCK-B receptor antagonist L-365,260 enhances morphine analgesia and prevents morphine tolerance in the rat

Cited by 259 publications

References 28 publications

Effect of CCK receptor antagonists on the antinociceptive, reinforcing and gut motility properties of morphine

Effect of CCK receptor antagonists on the antinociceptive, reinforcing and gut motility properties of morphine

Modulation of opioid antinociception by CCK at the supraspinal level: evidence of regulatory mechanisms between CCK and enkephalin systems in the control of pain

The roles of nerve growth factor and cholecystokinin in the enhancement of morphine analgesia in a rodent model of central nervous system inflammation

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