Intraadministration associations: Conditional hyperalgesia elicited by morphine onset cues.

Sokolowska, Marta; Siegel, Shepard; Kim, Joseph A.

doi:10.1037/0097-7403.28.3.309

Cited by 58 publications

(50 citation statements)

References 33 publications

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“…Adams and Holtzman (1990) had suggested conditioning to the interoceptive stimulus properties of opioid antagonists, wherein the interoceptive cues associated with low doses of the antagonist in the cumulative dose-effect function acquire predictive value of the withdrawal state elicited by the higher doses that follow later in the session. Siegel and colleagues (Sokolowska et al 2002) have similarly argued that interoceptive cues can contribute to other conditioned drug responses, such as conditioned hyperalgesia to morphine. The current data in which extra naloxone experience resulted in potentiation of naloxone potency only when extra experience was associated with the operant context would suggest that any predictive value of interoceptive antagonist cues is acquired in a contextspecific fashion.…”

Section: Effects Of Varying Context In Which Naloxone Is Experienced mentioning

confidence: 99%

Conditioning processes contribute to severity of naloxone-precipitated withdrawal from acute opioid dependence

2003

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Rationale: Single injections with morphine can induce a state of acute opioid dependence in humans and animals, typically measured as precipitated withdrawal, when an antagonist such as naloxone is administered 4-24 h after morphine. Repeated treatment with morphine results in further increases in naloxone potency, and prior work has shown that this progressive shift in naloxone potency requires repeated naloxone experience under some but not all experimental conditions. Objective: The current study sought to further characterize the experimental conditions that support naloxone experience-dependent and experience-independent potentiation of precipitated suppression of operant responding in morphine pretreated rats, and to assess more directly whether conditioning mechanisms may contribute to the former process. Methods: Rats trained on an FR15 schedule for food received a total of five vehicle or morphine injections (5.6 mg/kg SC) at 4, 8, or 22 h prior to an operant session in which a cumulative dose-effect function for naloxone-induced suppression of responding was determined. Separate groups of animals at each interval between morphine and naloxone received cumulative naloxone dosing after all morphine pretreatments (NAL all days) or after just the first and last morphine pretreatment (NAL first/last). Additional groups of rats at the 4 h MOR-NAL interval received most of their naloxone cumulative dose-effect experience in either the home cage or in the operant context with levers retracted. Results: Vehicle-pretreated (Morphine-naive) rats showed little change in the naloxone dose-effect function even after five cumulative dose-effect determinations. With a single morphine pretreatment, naloxone potency was increased at 4 or 8 h post-morphine, but not at 22 h. With repeated morphine treatment, all MOR-NAL intervals resulted in significant shifts in naloxone potency across treatment days even when naloxone was administered only after the first and last morphine pretreatment. However, much greater shifts in naloxone potency were observed at 4-h and 8-h intervals when naloxone was administered on all treatment days. At the 22 h MOR-NAL interval, there was no further potentiation in naloxone potency with additional naloxone experience provided on the intermediate days. Finally, when the repeated naloxone experience occurred in the home cage at the 4-h interval, naloxone potency was identical to that seen after limited naloxone experience (NAL first/last), and significantly less than naloxone potency in groups receiving repeated naloxone experience in the operant context. Conclusions: The results suggest that conditioned withdrawal mechanisms may play a significant role in the initial development of opioid dependence.

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Section: Effects Of Varying Context In Which Naloxone Is Experienced mentioning

confidence: 99%

Conditioning processes contribute to severity of naloxone-precipitated withdrawal from acute opioid dependence

2003

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“…The second order, longlasting memory state of morphine sets the opportunity for the encoding of morphine-induced pain in that state; once this encoding is established, subsequent opioid administrations reinstate retrieval (e.g., of pain; Bruins Slot and Colpaert, 1999b,c) and render retrieval increasingly dependent on that state (Bruins Slot and Colpaert, 2003). This statedependent retrieval may explain how subsequent opioid administrations reinstate pain in terms of both its sensory (Sokolowska et al, 2002), and, as here (Fig. 3B), affective/ motivational qualities (i.e., in a CPP paradigm; Mueller et al, 2002).…”

Section: -Htmentioning

confidence: 99%

“…Opioid pain occurs even upon single administration and can be conditioned to "morphine onset cues" to cause intra-administration associations (Sokolowska et al, 2002). Indeed, previous experience with heroin in withdrawal-at a time that opioid pain likely prevails-is necessary for subsequent heroin-seeking behavior to be enhanced when rats again experience withdrawal (Hutcheson et al, 2001).…”

Section: -Htmentioning

confidence: 99%

High-Efficacy 5-Hydroxytryptamine 1A Receptor Activation Counteracts Opioid Hyperallodynia and Affective Conditioning

Colpaert

Deseure²,

Stinus³

et al. 2005

J Pharmacol Exp Ther

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Pain may become intractable as tolerance develops to opioids and the opioids, paradoxically, induce pain. We examined the hypothesis that the analgesia produced by the novel analgesic and high-efficacy 5-hydroxytryptamine (5-HT) 1A receptor agonist (3-chloro-4-fluoro-phenyl)-[4-fluoro-4-{[(5-methyl-pyridin-2-ylmethyl)-amino]methyl}piperidin-1-yl]methanone, fumaric acid salt (F 13640) may counteract opioid-induced pain. In studies of the somatosensory quality of pain in infraorbital nerve-injured rats, morphine infusion (5 mg/day) by means of osmotic pumps initially caused analgesia (i.e., decreased the behavioral response to von Frey filament stimulation), followed by hyperallodynia and analgesic tolerance. Infusion of F 13640 (0.63 mg/day) prevented the development of opioid hyperallodynia and reversed opioid hyperallodynia once established. In studies of the affective/motivational quality of pain, F 13640 both prevented and reversed the conditioned place aversion induced by naloxone (0.04 mg/kg i.p.) in morphine-infused rats; F 13640 also prevented and reversed the conditioned place preference induced by morphine injections (7.5 mg/kg i.p.). The data confirm that opioids produce bidirectional hypo-and proalgesic actions, and offer initial evidence that high-efficacy 5-HT 1A receptor activation counteracts both the sensory and the affective/motivational qualities of opioid-induced pain. The data also indicate that F 13640 may be effective with opioidresistant pain. It further is suggested that opioid addiction may represent self-therapy of opioid-induced pathological pain.Although opioids produce powerful pain relief, pain may become intractable as tolerance develops to opioid analgesia; it has been proposed that this is because opioids may, paradoxically, induce pain. Indeed, a concept of signal transduction in central pain-processing systems (Colpaert, 1996) specifies that any input to such systems causes not a single effect but two dual effects that are bidirectional, or opposite in sign. Thus, morphine eventually causes not only analgesia as a "first order" effect but also a "second order" hyperalgesia that outlasts opioid receptor activation for some time. Upon chronic opioid exposure, the second order pain, or sensitization to nociceptive input, grows and neutralizes the first order analgesia. Considerable evidence now indicates that tolerance to opioid analgesia results from opioid-induced pain ("opioid pain"; here used to refer to hyperalgesia, allodynia, and hyperallodynia; Colpaert, 1996;Mao, 2002;Ossipov et al., 2003).Opioid pain is comprehensive, encompassing both the "physiological" (e.g., nociceptive) and the more recently identified (Scholz and Woolf, 2002) "pathological" (e.g., neuropathic) types of pain. Indeed, opioids not only produce hyperalgesia (i.e., an enhanced response to nociceptive stimulation; Colpaert, 1996) but also neuropathic-like allodynia (i.e., pain behaviors in response to innocuous stimuli; Ossipov et al., 2003). In human, opioid pain occurs after the intraoperative ...

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“…The method in these experiments consisted of giving a low dose of a drug, paired with a subsequent larger dose of the same drug. These studies have demonstrated acquisition and extinction effects when the low dose of the drug served as the CS (Cepeda-Benito & Short, 1997;Greeley, Lê, Poulos, & Cappell, 1984;Kim, Siegel, & Patenall, 1999;Sokolowska, Siegel, & Kim, 2002). However, these experiments have not compared the relative effectiveness of arbitrary versus drug cues as signals for subsequent drug administration and have not examined such manipulations as blocking, CS-US interval effects, or second-order conditioning.…”

Section: Us-us Versus Cs-us Learningmentioning

confidence: 99%

Learning with arbitrary versus ecological conditioned stimuli: Evidence from sexual conditioning

Domjan

Cusato

Krause

2004

Psychonomic Bulletin & Review

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Laboratory investigations of Pavlovian conditioning typically involve the association of an arbitrary conditioned stimulus (CS) with an unconditioned stimulus (US) that has no inherent relation to the CS. However, arbitrary CSs are unlikely to become conditioned outside the laboratory, because they do not occur often enough with the US to result in an association. Learning under natural circumstances is likely only if the CS has a preexisting relation to the US. Recent studies of sexual conditioning have shown that in contrast to an arbitrary CS, an ecologically relevant CS is resistant to blocking, extinction, and increases in the CS-US interval and results in sensitized responding and stronger secondorder conditioning. Although the mechanisms of these effects are not fully understood, these findings have shown that signature learning phenomena are significantly altered when the kinds of stimuli that are likely to become conditioned under natural circumstances are used. The implications of these findings for an ecological approach to the study of learning are discussed.

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Intraadministration associations: Conditional hyperalgesia elicited by morphine onset cues.

Cited by 58 publications

References 33 publications

Conditioning processes contribute to severity of naloxone-precipitated withdrawal from acute opioid dependence

Conditioning processes contribute to severity of naloxone-precipitated withdrawal from acute opioid dependence

High-Efficacy 5-Hydroxytryptamine 1A Receptor Activation Counteracts Opioid Hyperallodynia and Affective Conditioning

Learning with arbitrary versus ecological conditioned stimuli: Evidence from sexual conditioning

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