Cholecystokinin gene expression in rat amygdaloid neurons: normal distribution and effect of morphine tolerance

Pu, Su-Fen; Zhuang, Hui-Xin; Zhengbao, Lu; Wu, Xiru; Han, Ji-Sheng

doi:10.1016/0169-328x(94)90249-6

Cited by 34 publications

(10 citation statements)

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“…Consistent with this, CCK B receptors are found throughout the amygdala and, in particular, are highly concentrated in the lateral, basolateral, and cortical nuclei of the amygdala (Larssen and Rehfeld, 1979;McDonald, 1985;Vanderhaeghen, 1985;Ingram et al, 1989;Schiffmann and Vanderhaeghen, 1991;Pu et al, 1994). In contrast, when both injection cannulae were located dorsal, ventral, medial, or lateral to the amygdala, infusions of pentagastrin had no effect on startle responses.…”

Section: Discussionsupporting

confidence: 48%

“…The amygdala plays a critical role in mediating the behavioral and autonomic responses to fear and anxiety and, in particular, the potentiation of startle by "fear"-or "anxiety"-evoking stimuli (see, for example, Davis, 1992). Furthermore, CCK-containing neurons are distributed throughout the amygdaloid complex and, in particular, are concentrated in the lateral, basolateral, and cortical nuclei of the amygdala (Larssen and Rehfeld, 1979;McDonald, 1985;Vanderhaeghen, 1985;Ingram et al, 1989;Schiffmann and Vanderhaeghen, 1991;Pu et al, 1994).…”

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confidence: 99%

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Activation of Amygdala Cholecystokinin_BReceptors Potentiates the Acoustic Startle Response in the Rat

Frankland

Josselyn

Bradwejn³

et al. 1997

J. Neurosci.

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The acoustic startle reflex is a sensitive index of "anxiety" and "fear." Potentiation of startle by conditioned and unconditioned fear stimuli appears to be mediated by the amygdala. Cholecystokinin B (CCK B ) agonists increase "anxiety" in laboratory animals and induce "panic" in humans. Here, we investigate the role CCK B receptor-mediated mechanisms in the amygdala in the potentiation of startle. First, intra-amygdala infusions of the CCK B receptor agonist pentagastrin (0, 0.01, 0.1, 1, and 10 nM) produced a dose-related potentiation of acoustic startle responses. At the highest dose, startle amplitudes were increased up to 90% above preinfusion baseline levels. Second, similar infusions of pentagastrin had no effect on locomotor activity over the same time course, showing that increases in startle responsivity after infusions of pentagastrin are not attributable to nonspecific changes in motor activity. Third, infusions of similar doses of pentagastrin into the striatum or nucleus accumbens did not potentiate startle responses. Fourth, pretreatment with the CCK B receptor antagonist L-365,260 (0.1 mg/kg, i.p.) attenuated the potentiation of startle produced by intra-amygdala infusions of pentagastrin. Finally, intra-amygdala infusion of the CCK B receptor-selective antagonist PD-135158 (10 g) blocked the potentiation of startle produced by i.c.v. infusions of pentagastrin, suggesting that i.c.v. infusions of pentagastrin potentiate startle responses via activation of amygdala CCK B receptors. These results show that amygdala CCK B receptor-mediated mechanisms are involved in the potentiation of acoustic startle responses.

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Section: Discussionsupporting

confidence: 48%

mentioning

confidence: 99%

Activation of Amygdala Cholecystokinin_BReceptors Potentiates the Acoustic Startle Response in the Rat

Frankland

Josselyn

Bradwejn³

et al. 1997

J. Neurosci.

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“…Furthermore, CCK mRNA expression increases in the amygdala following repeated morphine administration, suggesting that the amygdala is a critical locus for a CCKmediated compensatory mechanism that contributes to opioid tolerance 41 . We have demonstrated that CCK release in the amygdala is required for a contextually triggered compensatory action that maintains pain sensitivity in the presence of morphine.…”

Section: Discussionmentioning

confidence: 99%

A locus and mechanism of action for associative morphine tolerance

2000

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Repeated administration of an opioid in the presence of specific environmental cues can induce tolerance specific to that setting (associative tolerance). Prolonged or repeated administration of an opioid without consistent contextual pairing yields non-associative tolerance. Here we demonstrate that cholecystokinin acting at the cholecystokinin-B receptor is required for associative but not non-associative morphine tolerance. Morphine given in the morphineassociated context increased Fos-like immunoreactivity in the lateral amygdala and hippocampal area CA1. Microinjection of the cholecystokinin B antagonist L-365,260 into the amygdala blocked associative tolerance. These results indicate that cholecystokinin acting in the amygdala is necessary for associative tolerance to morphine's analgesic effect.The role of cholecystokinin (CCK) as an anti-opioid peptide is firmly established. CCK suppresses the analgesic effect of morphine and other μ-opioid receptor agonists 1,2 . CCK antagonists potentiate the analgesic effects of exogenous and endogenous μ-opioid receptor agonists 3-8 and enhance the inhibitory effect of morphine on nociceptive dorsal horn neurons 9,10 . Additionally, CCK antagonists impede the acquisition of morphine tolerance yet have no effect on morphine dependence or withdrawal 3,[11][12][13][14][15][16] . Although CCK antagonists potentiate the effects of opioids, they do not alter nociceptive threshold levels when administered independently 8,16 . There are two distinct CCK receptors (CCK-A and CCK-B) in the CNS [17][18][19][20] .Learning can contribute to drug tolerance [21][22][23][24][25][26][27] . When morphine administration is paired with specific environmental cues, these cues can act as conditioned stimuli that elicit a conditioned response opposing the agonist effect of morphine (associative tolerance). Although associative analgesic tolerance following repeated opioid administration is well established, the underlying neurobiological mechanisms are unknown.

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“…For example, a single s.c. injection of morphine produced a doubling of CCK mRNA content in the hypothala-mus and a threefold increase in the spinal cord (Ding and Bayer, 1993). Moreover, prolonged exposure to morphine has caused the upregulation of CCK in the brain and the spinal cord, and produced a tripling of proCCK mRNA in the hypothalamus and spinal cord, and a 97% increase in whole brain proCCK mRNA (Zhou et al, 1992;Ding and Bayer, 1993;Pu et al, 1994). Repeated injections of morphine was associated with a 2.6-fold increase immunoreactive CCK in the hypothalamus, a 2.1-fold increase in the spinal cord, and a 1.6-fold increase in the brainstem (Ding and Bayer, 1993).…”

Section: Blocking Opioid-induced Enhanced Abnormal Pain Restores Morpmentioning

confidence: 97%

Antinociceptive and nociceptive actions of opioids

et al. 2004

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Although the opioids are the principal treatment options for moderate to severe pain, their use is also associated with the development of tolerance, defined as the progressive need for higher doses to achieve a constant analgesic effect. The mechanisms which underlie this phenomenon remain unclear. Recent studies revealed that cholecystokinin (CCK) is upregulated in the rostral ventromedial medulla (RVM) during persistent opioid exposure. CCK is both antiopioid and pronociceptive, and activates descending pain facilitation mechanisms from the RVM enhancing nociceptive transmission at the spinal cord and promoting hyperalgesia. The neuroplastic changes elicited by opioid exposure reflect adaptive changes to promote increased pain transmission and consequent diminished antinociception (i.e., tolerance).

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Cholecystokinin gene expression in rat amygdaloid neurons: normal distribution and effect of morphine tolerance

Cited by 34 publications

References 34 publications

Activation of Amygdala Cholecystokinin_BReceptors Potentiates the Acoustic Startle Response in the Rat

Activation of Amygdala Cholecystokinin_BReceptors Potentiates the Acoustic Startle Response in the Rat

A locus and mechanism of action for associative morphine tolerance

Antinociceptive and nociceptive actions of opioids

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Cholecystokinin gene expression in rat amygdaloid neurons: normal distribution and effect of morphine tolerance

Cited by 34 publications

References 34 publications

Activation of Amygdala CholecystokininBReceptors Potentiates the Acoustic Startle Response in the Rat

Activation of Amygdala CholecystokininBReceptors Potentiates the Acoustic Startle Response in the Rat

A locus and mechanism of action for associative morphine tolerance

Antinociceptive and nociceptive actions of opioids

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Product

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Activation of Amygdala Cholecystokinin_BReceptors Potentiates the Acoustic Startle Response in the Rat

Activation of Amygdala Cholecystokinin_BReceptors Potentiates the Acoustic Startle Response in the Rat