Excitatory amino acid receptor antagonist kynurenic acid attenuates rewarding potential of morphine

Bespalov, Anton; Dumpis, M. A.; Piotrovsky, L. B.; Zvartau, Edwin

doi:10.1016/0014-2999(94)00462-5

Cited by 57 publications

(18 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Recent evidence supports the involvement of glutamate in physical and psychological morphine dependence (17,19,21,22). It has been reported that several non-competitive and competitive NMDA-receptor antagonists such as MK-801, ketamine and LY274614 (18, 20, 29, 30), and AMPA-receptor antagonists (31,32) attenuate the development of morphine dependence and the expression of morphine withdrawal.…”

Section: Discussionmentioning

confidence: 88%

Involvement of Glutamate Receptors Within the Central Nucleus of the Amygdala in Naloxone-Precipitated Morphine Withdrawal-Induced Conditioned Place Aversion in Rats

Watanabe

Nakagawa

Yamamoto

et al. 2002

Japanese Journal of Pharmacology

View full text Add to dashboard Cite

ABSTRACT-Chronic use of morphine leads to physical and psychological dependence. The amygdala is known to be involved in the expression of emotion such as anxiety and fear, and several studies have shown that the central nucleus of the amygdala (CeA) is involved in morphine dependence. In the present study, we investigated the role of glutamate receptors within the CeA in the negative affective component of morphine abstinence by evaluating naloxone-precipitated withdrawal-induced conditioned place aversion (CPA) in morphine-dependent rats. We found that microinjection of the AMPA/ kainate-glutamate-receptor antagonist CNQX (30 nmol / side) into the bilateral CeA significantly attenuated the naloxone-precipitated withdrawal-induced CPA, as well as several somatic signs, in morphine-dependent rats, without preference or aversive effects by itself in non-dependent rats. Furthermore, microinjection of the non-competitive NMDA-receptor antagonist MK-801 (30 nmol/ side) or competitive NMDA-receptor antagonist D-CPPene (0.01 and 0.1 nmol / side) into the CeA significantly attenuated the naloxone-precipitated morphine withdrawal-induced CPA, but not somatic withdrawal signs. These results suggest that the activation of AMPA / kainate and NMDA receptors within the CeA play a crucial role in the negative affective component of morphine abstinence.

show abstract

Section: Discussionmentioning

confidence: 88%

Involvement of Glutamate Receptors Within the Central Nucleus of the Amygdala in Naloxone-Precipitated Morphine Withdrawal-Induced Conditioned Place Aversion in Rats

Watanabe

Nakagawa

Yamamoto

et al. 2002

Japanese Journal of Pharmacology

View full text Add to dashboard Cite

show abstract

“…Numerous studies have demonstrated that glycine site antagonists and partial agonists share many of the pharmacological actions of directlyacting NMDA antagonists, but without their psychotomimetic effects (Anthony and Nevins 1993;Dunn et al 1992;Faiman et al 1994;Rundfeldt et al 1994;Trullas et al 1991; Cherkovsky 1995;Fossom et al 1995; KarczKubicha et al 1999). Also in contrast to directly acting NMDA antagonists, glycine site antagonists and partial agonists fail to display rewarding properties in CPP experiments (Bespalov et al 1994;Kotlinska and Biala 1999).…”

Section: Acpc (1-aminocyclopropanecarboxylic Acid) Is a Partial Agonimentioning

confidence: 99%

“…However, both classes of directly-acting NMDA antagonist support CPP in their own right (Tzschentke and Schmidt 1995;. By contrast, the glycine site antagonists kynurenic acid and L-701,324 share with ACPC the property of blocking the acquisition of cocaine-and morphine-induced place preference, but not themselves supporting place conditioning (Bespalov et al 1994;Biala 1999, 2000). This suggests that blockade of the acquisition of cocaine and morphine CPP, without intrinsic activity in this procedure, may be a general property of compounds that act as functional NMDA antagonists via the strychnine-insensitive glycine receptor.…”

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

View full text Add to dashboard Cite

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...

show abstract

“…Previously, experimenteradministered or self-administered infusions of various drugs of abuse such as psychomotor stimulants (Wise et al, 1977;Bauco and Wise, 1997;Kenny et al, 2003) and opiates (Bespalov et al, 1994) were shown to lower the reward threshold, indicating increased sensitivity to the rewarding effects of ICSS that likely arises through druginduced amplification of reward signals in the brain. Here, we directly investigated the short-and long-term actions of nicotine consumption on the sensitivity of brain reward systems in vivo by monitoring ICSS thresholds in rats with daily access to intravenous nicotine self-administration.…”

Section: Introductionmentioning

confidence: 99%

Nicotine Self-Administration Acutely Activates Brain Reward Systems and Induces a Long-Lasting Increase in Reward Sensitivity

Kenny

Markou

2005

Neuropsychopharmacol

242

204

View full text Add to dashboard Cite

Nicotine is a major component of tobacco smoke contributing to the initiation and persistence of the harmful tobacco habit in human smokers. The reinforcing effects of nicotine likely arise through its ability to stimulate brain circuitry mediating the detection and experiencing of natural rewards. Nevertheless, remarkably little is known concerning the acute or long-lasting actions of nicotine on brain reward systems in vivo. Here, we investigated the effects of intravenously self-administered nicotine (0.03 mg/kg/infusion, free base) on the sensitivity of brain reward systems, reflected in alterations of intracranial self-stimulation (ICSS) thresholds in rats. Rats selfadministered nicotine during 1 or 12 h daily sessions, with reward thresholds assessed 1 h before and 15 min after each self-administration session. Control rats remained nicotine naïve throughout. Nicotine self-administration increased the sensitivity of brain reward systems, detected by post-nicotine lowering of reward thresholds in 1 and 12 h rats. This nicotine-enhanced sensitivity of reward systems was reversed by the high-affinity nicotinic receptor antagonist dihydro-b-erythroidine (DHbE; 3 mg/kg). Surprisingly, nicotine-induced excitation of reward systems persisted for at least 36 days after nicotine self-administration had ceased. Overall, these data demonstrate that rats can voluntarily consume quantities of nicotine sufficient to increase the sensitivity of brain reward systems, an action likely crucial in establishing and maintaining the nicotine habit. Moreover, self-administered nicotine resets the sensitivity of reward systems to a new increased level, thereby imprinting an indelible 'memory' of its effects in reward systems, an action that so far appears unique to nicotine among drugs of abuse.

show abstract

Excitatory amino acid receptor antagonist kynurenic acid attenuates rewarding potential of morphine

Cited by 57 publications

References 35 publications

Involvement of Glutamate Receptors Within the Central Nucleus of the Amygdala in Naloxone-Precipitated Morphine Withdrawal-Induced Conditioned Place Aversion in Rats

Involvement of Glutamate Receptors Within the Central Nucleus of the Amygdala in Naloxone-Precipitated Morphine Withdrawal-Induced Conditioned Place Aversion in Rats

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

Nicotine Self-Administration Acutely Activates Brain Reward Systems and Induces a Long-Lasting Increase in Reward Sensitivity

Contact Info

Product

Resources

About