Long-term sensitization to the excitatory effects of morphine

Bartoletti, M.; Gaiardi, M.; Gubellini, G.; Bacchi, A.; Babbini, M.

doi:10.1016/0028-3908(83)90080-1

Cited by 92 publications

(40 citation statements)

References 8 publications

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“…In contrast, acute administration of opioids into the VTA results only in hypermotility (Kelley et al, 1980;Joyce and Iversen, 1979;Kalivas et al, 1983) as do acute intra-VP opioid injection (Baud et al, 1988;Austin and Kalivas, 1990;Napier, 1992;Alesdatter and Kalivas, 1993;Churchill and Kalivas, 1999;Johnson et al, 1996; current study). With repeated systemic administration of opiates, the initial motor depression is attenuated (likely reflecting tolerance to the cataleptic effects of morphine) and overall activity is robustly increased (ie sensitized) (Babbini and Davis, 1972;Babbini et al, 1975;Brady and Holtzman, 1981;Bartoletti et al, 1983;Johnson and Glick, 1993;current study). Multiple infusions of opioids into the NAc (Vezina et al, 1987;Cunningham et al, 1997), VTA (Joyce and Iversen, 1979;Vezina and Stewart, 1984;Kalivas et al, 1985;Vezina et al, 1987) and VP (present study), all result in hyperlocomotion, but as discussed below, the temporal nature of this effect differs among the regions.…”

Section: Discussionmentioning

confidence: 99%

“…As shown in Figure 1c, a shift occurred from normal exploratory behavior 10 min after the first morphine dose (ie day 1 score of 4 ± 0.7) to stereotypy interrupted with intense locomotor bursts (day 5 score of 9 ± 0.5). This profile is thought to reflect tolerance to the motor-depressive effects of morphine (Babbini and Davis, 1972;Babbini et al, 1975;Brady and Holtzman, 1981;Bartoletti et al, 1983;Johnson and Glick, 1993). Photobeam-detected motor activity for 20-60 min post-injection was low for days 1 and 5 ( Figures 1a and b), but the underlying behaviors differed.…”

Section: Experiments 1 Profiling Morphine-induced Behavioral Sensitizmentioning

confidence: 99%

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The Ventral Pallidum is Critically Involved in the Development and Expression of Morphine-Induced Sensitization

Mickiewicz

Dallimore

Napier

2008

Neuropsychopharmacol

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Repeated, intermittent exposure to drugs of abuse results in response enhancements to subsequent drug treatments, a phenomenon referred to as sensitization. As persistent neuronal sensitization may contribute to the long-lasting consequences of drug abuse, characterizing the neuroanatomical substrates of sensitization is providing insights into addiction. It is known that the ventral tegmental area (VTA) is necessary for induction, and expression involves the nucleus accumbens (NAc). We reveal here that the ventral pallidum (VP), a brain region reciprocally innervated by the VTA and the NAc, is a critical mediator of opiate-induced behavioral sensitization. Blockade of VP m-opioid receptors (via intra-VP CTOP injections) negated the ability of systemic administration of the opiate, morphine to induce motor sensitization, and for sensitized rats to subsequently express enhanced responding to a morphine challenge. Intra-VP morphine was sufficient to induce motor sensitization, and this sensitization was expressed following 17 days of withdrawal. Rats with a treatment history of intra-VP morphine demonstrated cross-sensitization to a challenge injection of systemically administered morphine. Conversely, repeated systemic treatments of morphine cross-sensitized to an intra-VP morphine challenge. These results indicate that activation of VP m-opioid receptors is sufficient to evoke behavioral sensitization and that these receptors are necessary for sensitized responding to systemic morphine. The study pioneers the concept that both development and expression of drug-induced sensitization are regulated by the VP. Thus, the VP is likely an important contributor to neuronal adaptations that underlie addiction.

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Section: Discussionmentioning

confidence: 99%

Section: Experiments 1 Profiling Morphine-induced Behavioral Sensitizmentioning

confidence: 99%

The Ventral Pallidum is Critically Involved in the Development and Expression of Morphine-Induced Sensitization

Mickiewicz

Dallimore

Napier

2008

Neuropsychopharmacol

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“…The phenomenon of behavioral sensitization or "reverse tolerance" refers to an increase in motor stimulatory and stereotypic behaviors of stimulant drugs [35,80,87]. Psychomotor stimulant drugs, such as cocaine and amphetamine, as well as mu opioid receptor agonists can elicit behavioral sensitization [1,34,90]. Kappa opioid receptor agonists, on the other hand, due to their inhibitory action on dopamine release and motor activity, block behavioral sensitization induced by psychostimulants [28,29,88].…”

Section: The Role Of Orl-1 Receptors In the Rewarding Action Of Buprementioning

confidence: 99%

Buprenorphine: A Unique Drug with Complex Pharmacology

Lutfy

Cowan²

2004

280

232

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Buprenorphine, an opioid with mixed agonist-antagonist activity at classical opioid receptors, has been approved recently for the treatment of opioid dependency. Buprenorphine is also used as an analgesic. The buprenorphine dose-response curve is sometimes submaximal, or even bell-shaped, in nociceptive assays, depending upon the nature and intensity of the noxious stimulus. Moreover, buprenorphine, when administered with full agonists, such as morphine, antagonizes the action of these drugs. Partial agonism at the mu opioid receptor and, in some cases, antagonism at the kappa or delta opioid receptor have been considered as possible underlying mechanisms for the ceiling effect and bell-shaped dose-response curve of buprenorphine. While ceiling effects can be explained by partial agonist activity of buprenorphine, the bell-shaped dose-response curve cannot be a consequence of this property of the drug. Recently, buprenorphine has been shown to activate the opioid receptor-like (ORL-1; also known as NOP) receptor. Supraspinal activation of the ORL-1 receptor counteracts the antinociceptive and rewarding actions of morphine, raising the possibility that these actions of buprenorphine can also be altered by its ability to concomitantly activate the ORL-1 receptor. The use of molecular biological techniques has advanced our knowledge regarding the role of opioid receptors in modulation of pain and reward. In particular, generation of opioid receptor knockout mice has proven useful in this regard. Indeed, using knockout mice, we have recently shown that the antinociceptive effect of buprenorphine mediated primarily by the mu opioid receptor is attenuated by the ability of the drug to activate the ORL-1 receptor. Thus, the goal of this review is to provide evidence demonstrating that the ORL-1 receptor plays a functional role not only in the antinociceptive effect of buprenorphine but also in other actions of the drug as well.

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“…Tolerance to the depressant effects of morphine following several weeks of morphine abstinence has been reported previously (Bartoletti et al, 1983;Vanderschuren et al, 1997). The absence of the locomotor-depressant effects of acute morphine in post-dependent animals indicates that tolerance/habituation to some properties of morphine persist even after 6-8 weeks of abstinence.…”

Section: Discussionmentioning

confidence: 84%

Incentive Learning for Morphine-Associated Stimuli During Protracted Abstinence Increases Conditioned Drug Preference

Smith

Aston‐Jones

2013

Neuropsychopharmacol

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Previous studies from our laboratory found that rats express increased preference for drug-paired stimuli following 2 or 5 weeks of protracted abstinence from chronic drug exposure as compared with naive animals. Here, we show that this increased morphine place preference depends upon experiencing drug-stimulus pairings specifically in the abstinent state, indicating a critical role for incentive learning. Male Sprague Dawley rats were initially conditioned for morphine place preference (8 mg/kg) and then made dependent on morphine (by subcutaneous morphine pellets) and subjected to forced abstinence. Place preference was tested every 1-2 weeks with no additional drug-cue conditioning. In this paradigm, there was no difference between morphine-pelleted (dependent) and placebopelleted (non-dependent) rats in place preference at any time during abstinence (up to 6 weeks). However, these same morphinepelleted rats expressed significantly increased preference when they were subsequently re-conditioned for morphine place preference during protracted abstinence. Placebo-pelleted rats did not show enhanced preference after re-conditioning. These findings reveal that incentive learning has a key role in increased morphine place preference when drug is experienced during protracted abstinence. This indicates that incentive learning is involved not only in instrumental responding (as previously reported), but also in updating Pavlovianconditioned responses to morphine-associated stimuli. Therefore, enhanced morphine preference is not a direct consequence of the negative affective state of abstinence, but instead reflects increased acquisition of morphine-stimulus associations during abstinence. These results indicate that, during the development of addiction in humans, drug-associated stimuli acquire increasingly stronger incentive properties each time they are re-experienced.

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Long-term sensitization to the excitatory effects of morphine

Cited by 92 publications

References 8 publications

The Ventral Pallidum is Critically Involved in the Development and Expression of Morphine-Induced Sensitization

The Ventral Pallidum is Critically Involved in the Development and Expression of Morphine-Induced Sensitization

Buprenorphine: A Unique Drug with Complex Pharmacology

Incentive Learning for Morphine-Associated Stimuli During Protracted Abstinence Increases Conditioned Drug Preference

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