Antagonists of N-methyl-D-aspartate receptors partially prevent the development of cocaine sensitization

Haracz, John L.; Belanger, Susan A.; MacDonall, James S.; Sircar, Ratna

doi:10.1016/0024-3205(95)02229-c

Cited by 34 publications

(22 citation statements)

References 27 publications

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“…Selective ablation of NR1 expression in striatal neurons has been used to study the role of NMDA receptor signaling in the acquisition of behavioral sensitization and conditioned place preference (Heusner and Palmiter, 2005;Agatsuma et al, 2010). These studies clarify previous research showing that blockade of NMDA receptor is disruptive to the development of sensitization and place preference (Haracz et al, 1995;Kim et al, 1996;Li and Wolf, 1999).…”

Section: Introductionsupporting

confidence: 56%

Altered Acquisition and Extinction of Amphetamine-Paired Context Conditioning in Genetic Mouse Models of Altered NMDA Receptor Function

Benneyworth

Coyle

2012

Neuropsychopharmacol

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Repeated intermittent exposure to amphetamine (AMPH) results in the development of persistent behavioral and neurological changes. When drug exposure is paired with a specific environment, contextual cues can control conditioned responses, context-specific sensitization, and alterations in dendritic morphology in the nucleus accumbens (NAc). Intact N-methyl-D-aspartate (NMDA) glutamate receptor signaling is thought to be required for associative learning. The acquisition of context-specific behavioral sensitization to AMPH and extinction of conditioned hyperactivity have been investigated in two genetically modified mouse strains: the serine racemase homozygous knockout (SRÀ/À) and glycine transporter 1 heterozygous mutant (GlyT1À/ + ). These strains have reciprocally altered NMDA receptor co-agonists, D-serine and glycine, levels that result in decreased (SRÀ/À) or increased (GlyT1À/ + ) NMDA receptor signaling. AMPH-induced changes in dendritic morphology in the NAc were also examined. SRÀ/À mice showed reduced expression of context-specific sensitization and conditioned hyperactivity. However, the conditioned hyperactivity in these mice is completely resistant to extinction. Extinction reversed AMPH-induced increased in NAc spine density in wild-type but not SRÀ/À mice. GlyT1 À/ + mice showed a more rapid acquisition of sensitization, but no alteration in the extinction of conditioned hyperactivity. The SRÀ/À data demonstrate that a genetic model of NMDA receptor hypofunction displays a reduced ability to extinguish conditioned responses to drug-associated stimuli. Findings also demonstrate that the morphological changes in the NAc encode conditioned responses that are sensitive to extinction and reduced NMDA receptor activity. NMDA receptor hypofunction may contribute to the comorbidity of substance abuse in schizophrenia.

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Section: Introductionsupporting

confidence: 56%

Altered Acquisition and Extinction of Amphetamine-Paired Context Conditioning in Genetic Mouse Models of Altered NMDA Receptor Function

Benneyworth

Coyle

2012

Neuropsychopharmacol

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“…Considering the body of evidence suggesting that blockade of NMDA receptors prevents the development of behavioral sensitization to psychostimulants, the diminished response to repeated administration of cocaine was not completely unexpected (Li et al, 1999;Haracz et al, 1995;Kalivas and Alesdatter, 1993;Stewart and Druhan, 1993;Wolf and Jeziorski, 1993;Heusner and Palmiter, 2005;Miyamoto Y et al, 2004). More surprising was that some level of sensitization to cocaine still persisted and that amphetamine sensitization developed to the same extent in NR1 mutant animals as in wild types.…”

Section: Discussionmentioning

confidence: 99%

“…However, low doses of MK-801 (0.2-0.3 mg/kg) have been reported to disrupt sensitization (Li et al, 1999;Haracz et al, 1995;Kalivas and Alesdatter, 1993;Stewart and Druhan, 1993;Wolf andJeziorski, 1993, Vanderschuren andKalivas, 2000;Wolf, 1998). At these doses in vivo, NMDA receptor occupancy and antagonism by MK-801 is only 40-50% (Price et al, 1988;Murray et al, 2000).…”

Section: Discussionmentioning

confidence: 99%

“…This altered state of responsiveness involves long-lasting changes in gene expression, electrophysiological properties, and even morphology of striatal medium spiny neurons (Yao et al, 2004;Thomas et al, 2001;Nestler, 2001;Bibb et al, 2001;Robinson and Kolb, 1997;Koob et al, 1998). Several groups have reported disrupted sensitization to psychostimulants and dopaminergic agonists using pharmacological tools to block NMDA receptor function (Li et al, 1999;Haracz et al, 1995;Kalivas and Alesdatter, 1993;Stewart and Druhan, 1993;Wolf and Jeziorski, 1993;Karler et al, 1989); however, variations in the timing and context of NMDA antagonist administration may affect different aspects of the biological process underlying sensitization (Tzschentke and Schmidt, 1998;Ranaldi et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

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Genetic NMDA Receptor Deficiency Disrupts Acute and Chronic Effects of Cocaine but not Amphetamine

Ramsey

Laakso

Cyr

et al. 2008

Neuropsychopharmacol

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NMDA receptor-mediated glutamate transmission is required for several forms of neuronal plasticity. Its role in the neuronal responses to addictive drugs is an ongoing subject of investigation. We report here that the acute locomotor-stimulating effect of cocaine is absent in NMDA receptor-deficient mice (NR1-KD). In contrast, their acute responses to amphetamine and to direct dopamine receptor agonists are not significantly altered. The striking attenuation of cocaine's acute effects is not likely explained by alterations in the dopaminergic system of NR1-KD mice, since most parameters of pre-and postsynaptic dopamine function are unchanged. Consistent with the behavioral findings, cocaine induces less c-Fos expression in the striatum of these mice, while amphetamine-induced c-Fos expression is intact. Furthermore, chronic cocaine-induced sensitization and conditioned place preference are attenuated and develop more slowly in mutant animals, but amphetamine's effects are not altered significantly. Our results highlight the importance of NMDA receptor-mediated glutamatergic transmission specifically in cocaine actions, and support a hypothesis that cocaine and amphetamine elicit their effects through differential actions on signaling pathways.

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“…A few studies have used cleaner, competitive NMDAR antagonists in examining psychostimulant-induced sensitization [45,46,17,20,27,29,41,[47][48][49][50][51][52][53][54]. For example, Wolf et al [27] used CGS19755 and found a "clean block" of amphetamine sensitization -i.e., stereotyped and locomotor behavior did not increase with repeated administration in rats co-administered CGS19755 with amphetamine.…”

Section: Introductionmentioning

confidence: 99%

The competitive NMDA receptor antagonist CPP disrupts cocaine-induced conditioned place preference, but spares behavioral sensitization

Carmack

Kim²,

Sage³

et al. 2013

Behavioural Brain Research

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h i g h l i g h t sCPP co-administration with cocaine altered the acute response to cocaine. NMDAR antagonism with CPP had no effect on cocaine-induced behavioral sensitization. NMDAR antagonism with CPP abolished cocaine-induced conditioned place preference. a r t i c l e i n f o a b s t r a c tRecently, the notion that memory and addiction share similar neural substrates has become widely accepted. N-methyl-d-aspartate receptors (NMDAR) are the cornerstones of synaptic models of memory. The present study examined the effect of the competitive NMDAR antagonist CPP on the induction of behavioral sensitization and conditioned place preference to cocaine. Conditioned place preference is an associative memory model of drug seeking, while sensitization is a non-associative model of the transition from casual to compulsive use. There were three principal findings: (1) co-administration of CPP and cocaine altered the acute response to cocaine, suggesting a direct interaction between the two drugs; (2) NMDAR antagonism had no effect on behavioral sensitization; and (3) NMDAR antagonism abolished conditioned place preference. A review of prior evidence supporting a role for NMDARs in sensitization suggests that NMDAR antagonists directly interfere with cocaine's psychostimulant effects, and this interaction could be misinterpreted as a disruption of sensitization. Finally, we suggest that addiction recruits multiple kinds of plasticity, with sensitization recruiting NMDAR-independent mechanisms.

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Antagonists of N-methyl-D-aspartate receptors partially prevent the development of cocaine sensitization

Cited by 34 publications

References 27 publications

Altered Acquisition and Extinction of Amphetamine-Paired Context Conditioning in Genetic Mouse Models of Altered NMDA Receptor Function

Altered Acquisition and Extinction of Amphetamine-Paired Context Conditioning in Genetic Mouse Models of Altered NMDA Receptor Function

Genetic NMDA Receptor Deficiency Disrupts Acute and Chronic Effects of Cocaine but not Amphetamine

The competitive NMDA receptor antagonist CPP disrupts cocaine-induced conditioned place preference, but spares behavioral sensitization

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