Morphine preexposure facilitates morphine place preference and attenuates morphine taste aversion

Simpson, Gregory R; Riley, Anthony L.

doi:10.1016/j.pbb.2005.01.003

Cited by 86 publications

(65 citation statements)

References 31 publications

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“…However, morphine place preference was increased in postdependent rats, as compared with the previous test and non-dependent rats, after they were re-conditioned for morphine CPP in the abstinent state (following 6-8 weeks of abstinence). Previous animal studies found that preexposure to morphine or cocaine increases subsequent place preference for those drugs (Gaiardi et al, 1991;Aston-Jones, 2001, 2003a;Harris et al, 2007b;Lett, 1989;Shippenberg and Heidbreder, 1995;Shippenberg et al, 1996;Simpson and Riley, 2005). However, the current results extend those studies by showing that enhanced morphine preference during protracted abstinence is dependent upon experiencing drug-cue pairings specifically in the abstinent state, indicating an important role of incentive learning for Pavlovian-conditioned responses.…”

Section: Discussionsupporting

confidence: 62%

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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Section: Discussionsupporting

confidence: 62%

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

Smith

Aston‐Jones

2013

Neuropsychopharmacol

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“…While sensitization and conditioned place preference are generally considered separate phenomena, pre-treated or sensitized animals do show significantly enhanced CPP relative to control animals (Lett, 1989;Shippenberg and Heidbreder, 1995;Simpson and Riley, 2005). Interestingly, we have previously shown pre-treatment with cocaine results in enhanced longterm potentiation (LTP), an affect which could be expected to enhance learned associations such as those involved in CPP (Thompson et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

“…Previously sensitized animals exhibit significantly enhanced conditioned place preference (CPP) relative to control animals (Lett, 1989;Shippenberg and Heidbreder, 1995;Simpson and Riley, 2005). Place conditioning typically involves repeatedly pairing a compartment with a specific stimulus while pairing a separate distinct compartment with a neutral stimulus.…”

Section: Introductionmentioning

confidence: 99%

Simultaneous expression of cocaine-induced behavioral sensitization and conditioned place preference in individual rats

Seymour

Wagner

2008

Brain Research

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Conditioned place preference and locomotor sensitization are rodent behavioral models commonly used to investigate the actions of drugs of abuse. However, few studies have examined both paradigms in the same group of animals. We were interested in developing a combined protocol which successfully induced both conditioned place preference and sensitization simultaneously in cocainetreated Sprague Dawley rats in order to test the hypothesis that the magnitude of these two phenomena would be positively correlated. We used an open-field with a removable place preference insert to assess these measures independently. Cocaine-conditioned animals demonstrated a significant shift in preference for the drug-paired compartment and a sensitized locomotor response which was not observed in saline-conditioned animals challenged with cocaine. There was no significant relationship between locomotor sensitization and conditioned place preference in individual animals. We further examined these results with respect to each rats' initial response to cocaine, response to a novel environment and central zone entries in an open-field. Locomotor sensitization demonstrated an inverse correlation with the initial cocaine response. In contrast, conditioned place preference demonstrated an inverse correlation with the centre response. These results demonstrate that the combination of the acute cocaine response and the centre response in a novel open field environment can be used to indicate the propensity of a given rat to exhibit either behavioral sensitization or conditioned place preference; however, it seems that sensitization and place preference are not necessarily co-expressed to a similar extent in the same individual animal.

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“…As drug abuse potential can be envisaged as a balance between rewarding and aversive effects (Hutchison and Riley, 2008;Simpson and Riley, 2005;Wise et al, 1976), it can be hypothesized that the components of the appetitive properties of addicting drugs might result from both direct activation of neural reward pathways and suppression of responses in neural circuits mediating aversion. Indeed, one of the hallmarks of drug addiction is the perseverance of drug taking despite of negative and unpleasant consequences of drug use.…”

Section: Introductionmentioning

confidence: 99%

Effects of Drugs of Abuse on Putative Rostromedial Tegmental Neurons, Inhibitory Afferents to Midbrain Dopamine Cells

Lecca

Melis

Luchicchi

et al. 2010

Neuropsychopharmacol

139

163

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Recent findings have underlined the rostromedial tegmental nucleus (RMTg), a structure located caudally to the ventral tegmental area, as an important site involved in the mechanisms of aversion. RMTg contains g-aminobutyric acid neurons responding to noxious stimuli, densely innervated by the lateral habenula and providing a major inhibitory projection to reward-encoding midbrain dopamine (DA) neurons. One of the key features of drug addiction is the perseverance of drug seeking in spite of negative and unpleasant consequences, likely mediated by response suppression within neural pathways mediating aversion. To investigate whether the RMTg has a function in the mechanisms of addicting drugs, we studied acute effects of morphine, cocaine, the cannabinoid agonist WIN55212-2 (WIN), and nicotine on putative RMTg neurons. We utilized single unit extracellular recordings in anesthetized rats and whole-cell patch-clamp recordings in brain slices to identify and characterize putative RMTg neurons and their responses to drugs of abuse. Morphine and WIN inhibited both firing rate in vivo and excitatory postsynaptic currents (EPSCs) evoked by stimulation of rostral afferents in vitro, whereas cocaine inhibited discharge activity without affecting EPSC amplitude. Conversely, nicotine robustly excited putative RMTg neurons and enhanced EPSCs, an effect mediated by a7-containing nicotinic acetylcholine receptors. Our results suggest that activity of RMTg neurons is profoundly influenced by drugs of abuse and, as important inhibitory afferents to midbrain DA neurons, they might take place in the complex interplay between the neural circuits mediating aversion and reward.

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Morphine preexposure facilitates morphine place preference and attenuates morphine taste aversion

Cited by 86 publications

References 31 publications

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

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

Simultaneous expression of cocaine-induced behavioral sensitization and conditioned place preference in individual rats

Effects of Drugs of Abuse on Putative Rostromedial Tegmental Neurons, Inhibitory Afferents to Midbrain Dopamine Cells

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