Mesolimbic NMDA receptors are implicated in the expression of conditioned morphine reward

Popik, Piotr; Kolasiewicz, Wacław

doi:10.1007/pl00005354

Cited by 56 publications

(45 citation statements)

References 47 publications

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“…Thus, despite the lack of a direct ethanol effect on FOS expression in the VTA of DBA/2J mice (Hitzemann and Hitzemann, 1997), our finding of conditioned FOS increases in this brain area appears consistent with many other findings implicating this area in the mediation of ethanol's primary reinforcing effects. Involvement of the VTA in ethanol-induced conditioning is also consistent with findings from several studies suggesting that this brain area plays an important role in place preference conditioning induced by other abused drugs (Gholami et al, 2003;Harris and Aston-Jones, 2003;Neumaier et al, 2002;Popik and Kolasiewicz, 1999). In all of these studies, effects on CPP were believed to be due to modulation of VTA dopamine cells.…”

Section: Conditioned Changes In Fossupporting

confidence: 89%

FOS expression induced by an ethanol-paired conditioned stimulus

Hill

Ryabinin

Cunningham

2007

Pharmacology Biochemistry and Behavior

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To identify brain areas involved in ethanol-induced Pavlovian conditioning, brains of male DBA/2J mice were immunohistochemically analyzed for FOS expression after exposure to a conditioned stimulus (CS) previously paired with ethanol (2 g/kg) in two experiments. Mice were trained with a procedure that normally produces place preference (Before: ethanol before the CS) or one that normally produces place aversion (After: ethanol after the CS). Control groups received unpaired ethanol injections in the home cage (Delay) or saline only (Naïve). On the test day, mice were exposed to the 5-min CS 90 min before sacrifice. Before groups showed a conditioned increase in activity, whereas the After group showed a conditioned decrease in activity. FOS expression after a drug-free CS exposure was significantly higher in Before-group mice than in control mice in the bed nucleus of the stria terminalis (Exp. 1) and anterior ventral tegmental area (Exps. 1-2). Conditioned FOS responses were also seen in areas of the extended amygdala and hippocampus (Exp. 2). However, no conditioned FOS changes were seen in any brain area examined in After-group mice. Overall, these data suggest an important role for the mesolimbic dopamine pathway, extended amygdala and hippocampus in ethanol-induced conditioning.

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Section: Conditioned Changes In Fossupporting

confidence: 89%

FOS expression induced by an ethanol-paired conditioned stimulus

Hill

Ryabinin

Cunningham

2007

Pharmacology Biochemistry and Behavior

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“…Therefore, one could expect that the inhibition of NMDA receptors might produce a reverse effect. Consistent with this idea, we have previously shown that administration of the NMDA receptor antagonist into VTA inhibits the expression of place preference conditioned with morphine (Popik and Kolasiewicz, 1999).…”

Section: Discussionsupporting

confidence: 61%

Reinstatement of Morphine-Conditioned Reward is Blocked by Memantine

Popik

Wróbel

Bisaga

2005

Neuropsychopharmacol

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Protection of abstinent individuals from relapse is the main goal of drug dependence treatment. Relapse is frequently precipitated by exposure to small doses of the drug of abuse or exposure to the environment that was previously associated with the drug. Mice exposed to morphine (10 mg/kg) in a unique test-box environment display a conditioned place preference for this environment. Such preference can be extinguished by subsequent pairing of physiological saline administration with the same environment. Once extinguished, the original place preference can be reinstated after a priming dose (1-2.5 mg/kg) of morphine is given. However, mice treated with 7.5 (but not 3.75) mg/kg of memantine (the glutamate/NMDA receptor antagonist) during the extinction phase were insensitive to morphine's ability to reinstate the place preference 2 days after extinction conditionings. Effect of memantine was also observed when priming dose of morphine was given 21 days after extinction conditionings. In contrast, morphine's ability to reinstate conditioned response was not affected by treatment with 10 mg/kg of chlordiazepoxide, 0.5 mg/kg of LSD-25, or 1 mg/kg of morphine given during extinction conditionings. A separate experiment demonstrated that memantine (7.5 mg/kg) treatment did not affect learning. We show for the first time that memantine treatment during extinction conditionings may abolish the ability of drug-related cues to evoke reinstatement, suggesting that this NMDA receptor antagonist can be useful in preventing relapse in opioid dependent individuals.

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“…These data are largely consistent with those of previous studies, which, however, have been confined to morphine and cocaine. Thus, both the acquisition and the expression of morphine place conditioning was blocked by glycine antagonists (MRZ 2/570 and L-701,324) and by an uncompetitive NMDA antagonist (Popik et al 1998); in a later study, a competitive NMDA antagonist was shown to block the expression of morphine place preference when administered systemically or directly within the nucleus accumbens or ventral tegmental area (Popik and Kolasiewicz 1999). In contrast, the uncompetitive NMDA antagonist dizocilpine blocked the acquisition but not the expression of cocaine place preference (Cervo and Samanin 1995), and the same results have been reported previously for ACPC (Kotlinska and Biala 2000).…”

Section: Effects Of Acpc On the Expression Of Drugconditioned Place Pmentioning

confidence: 93%

“…Within this region, there are extensive bi-directional interactions between DA inputs from the ventral tegmental area and glutamatergic inputs from forebrain sites, such as hippocampus and amygdala, that are known to be involved in place conditioning (Everitt et al 1991;Tzschentke 1998). These DA-NMDA receptor interactions within the accumbens shell are a likely candidate for a site at which both DA and NMDA receptor antagonists block the acquisition of drug-conditioned place preferences (Tzschentke andSchmidt 1995, 1997;Popik and Kolasiewicz 1999). However, in addition to direct DA-NMDA interactions, DA and glutamate synapses are co-localized on the dendritic spines of medium spiny neurons in the nucleus accumbens (Gerfen 2000;Onn et al 2000).…”

Section: Mechanisms Of Acpc Effects On the Acquisition Of Drug-conditmentioning

confidence: 99%

Selective Blockade of Drug-induced Place Preference Conditioning by ACPC, a Functional NDMA-receptor Antagonist

Papp

Gruca

Willner

2002

Neuropsychopharmacology

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ACPC (1-aminocyclopropanecarboxylic acid) is a partial agonist at the strychnine-insensitive glycine receptor site on the NMDA receptor complex, and a functional NMDA antagonist. A series of experiments was conducted to assess the effects of ACPC in a biased place conditioning paradigm. As previously reported, ACPC itself did not support either appetitive or aversive place conditioning. However, co-administration of ACPC (200 mg/kg) blocked the acquisition of place preferences conditioned using a variety of psychoactive drugs (amphetamine, cocaine, nomifensine, diazepam, morphine, nicotine). No tolerance was seen to this effect following two weeks of chronic ACPC administration. Overall, ACPC did not affect the expression of place conditioning when administered immediately before the post-conditioning test. However, these effects appeared somewhat variable between drugs, and further analysis showed that ACPC did block the expression of preferences conditioned with some drugs (diazepam, morphine, nicotine), but not others (amphetamine, cocaine, nomifensine). The effects of ACPC could not be accounted for by state dependence, as ACPC blocked morphine and cocaine place preferences when administered during both the acquisition and the expression phase of conditioning. In contrast to the blockade by ACPC of drug-induced place preferences, ACPC had no effect on the acquisition of place preferences conditioned using a variety of natural non-drug reinforcers (food, sucrose, social interaction, novelty). ACPC also had no effect on the acquisition of drug-induced place aversions (naloxone, picrotoxin The treatment of drug addiction has two targets: cessation or reduction of use, and maintenance of those gains. During the maintenance phase, a number of factors have been identified that predispose to relapse. These include stimuli associated with drug taking (O'Brien et al. 1998). The place preference conditioning procedure has been used extensively as an animal model for investigating the rewarding properties of drug-conditioned stimuli. In this procedure, 27 , NO . 5 the animal experiences the effects of a drug while confined in a distinctive environment; subsequently the animal is offered a choice between the drug-paired environment and an environment that has been experienced in the drug-free state. Subject to certain methodological considerations, a preference for the drug-paired environment is interpreted to mean that the environment has acquired secondary reinforcing properties as a consequence of its pairing with a primary reinforcer. Drugs that support the development of a conditioned place preference (CPP) are generally those that are abused by people (e.g. psychostimulants, opioids, benzodiazepines, alcohol, nicotine), while drugs that do not support CPP are typically not abused (e.g. neuroleptics, antidepressants, antihistamines) (Carr et al. 1989;Schechter and Calcagnetti 1993;Calcagnetti and Schechter 1998;Tzschentke 1998). In addition to drug rewards, CPP can also be used to study the reinforcing prop...

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Mesolimbic NMDA receptors are implicated in the expression of conditioned morphine reward

Cited by 56 publications

References 47 publications

FOS expression induced by an ethanol-paired conditioned stimulus

FOS expression induced by an ethanol-paired conditioned stimulus

Reinstatement of Morphine-Conditioned Reward is Blocked by Memantine

Selective Blockade of Drug-induced Place Preference Conditioning by ACPC, a Functional NDMA-receptor Antagonist

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