The mGlu2/3 receptor agonist LY379268 blocks the expression of locomotor sensitization by amphetamine

Kim, Jeong-Hoon; Vezina, Paul

doi:10.1016/s0091-3057(02)00827-4

Cited by 52 publications

(43 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although we did not study locomotor activity or behavioral sensitization in relation to glutamate release in NAcc in this report, it is likely that glutamate release has a modulatory role in locomotion via activation of NMDA receptors (Shoblock et al, 2003), as well as via activation of other glutamate receptor subtypes (Giorgetti et al, 2001;Kim and Vezina, 2002). In the current report, the augmented release of glutamate following acute amphetamine in EC rats, which was blocked completely by MK-801, may explain the exaggerated hyperactivity in response to acute amphetamine noted previously in EC rats (Bowling et al, 1993;Bowling and Bardo 1994).…”

Section: Discussionmentioning

confidence: 87%

Environmental enrichment increases amphetamine-induced glutamate neurotransmission in the nucleus accumbens: A neurochemical study

Rahman

Bardo

2008

Brain Research

View full text Add to dashboard Cite

In addition to dopamine (DA), evidence indicates that glutamatergic regulation of the mesolimbic reward pathway is involved in mediating the abuse-related effects of psychostimulants, including amphetamine. Since rats raised in an enrichment condition (EC) during development are more sensitive to the locomotor stimulant effects of acute amphetamine compared to rats raised in an impoverished condition (IC), the present study examined amphetamine-induced extracellullar glutamate and aspartate levels in the nucleus accumbens (NAcc) of EC and IC rats using in vivo microdialysis coupled with HPLC-electrochemical detection. Basal extracellular levels of glutamate or aspartate were not significantly different between EC and IC rats. Acute systemic amphetamine (0.5 or 2.0 mg/kg, sc) increased extracellular glutamate levels in NAcc of EC rats (137% or 305% of basal) and IC rats (120% or 187% of basal). Similarly, acute systemic amphetamine (0.5 or 2.0 mg/kg, sc) elevated aspartate levels in NAcc of EC rats (148% or 237% of basal) and IC rats (115% or 170% of basal). Glutamate levels were elevated by amphetamine to a greater extent in EC rats than in IC rats. Pretreatment with systemic MK-801 (0.25 mg/kg, ip), a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist, prevented the acute amphetamine-induced increase in extracellular glutamate and aspartate levels in NAcc. Overall, these results suggest that alterations in glutamate in the NAcc may be involved in the environment-dependent effects of amphetamine.

show abstract

Section: Discussionmentioning

confidence: 87%

Environmental enrichment increases amphetamine-induced glutamate neurotransmission in the nucleus accumbens: A neurochemical study

Rahman

Bardo

2008

Brain Research

View full text Add to dashboard Cite

show abstract

“…The physical environments that provided Contexts A and B were counterbalanced. Drugs LY379268 (0.3, 1.0, and 3.0 mg) was dissolved in 1.2 M NaOH solution (pH adjusted to 7.4) (Kim and Vezina, 2002;Kim et al, 2005). The bilateral intracranial doses of LY379268 were based on our previous report (Bossert et al, 2004).…”

Section: Apparatusmentioning

confidence: 99%

Activation of Group II Metabotropic Glutamate Receptors in the Nucleus Accumbens Shell Attenuates Context-Induced Relapse to Heroin Seeking

Bossert

Gray

Lü

et al. 2005

Neuropsychopharmacol

216

173

View full text Add to dashboard Cite

Using a rat relapse model, we previously reported that re-exposing rats to a drug-associated context, following extinction of operant responding in a different context, reinstates heroin seeking. In an initial pharmacological characterization, we found that the mGluR 2/3 agonist LY379268, which acts centrally to reduce evoked glutamate release, attenuates context-induced reinstatement of heroin seeking when injected systemically or into the ventral tegmental area, the cell body region of the mesolimbic dopamine system. Here, we tested whether injections of LY379268 into the nucleus accumbens (NAc), a terminal region of the mesolimbic dopamine system, would also attenuate context-induced reinstatement of heroin seeking. Rats were trained to self-administer heroin; drug infusions were paired with a discrete tone-light cue. Subsequently, lever pressing was extinguished in the presence of the discrete cue in a context that differed from the drug self-administration context in terms of visual, auditory, tactile, and circadian cues. After extinction of responding, LY379268 was injected to different groups of rats into the NAc core or shell or into the caudate-putamen, a terminal region of the nigrastriatal dopamine system. Injections of LY379268 into the NAc shell (0.3 or 1.0 mg) dose-dependently attenuated context-induced reinstatement of heroin seeking. Injections of 1.0 mg of LY379268 into the NAc core had no effect, while a higher dose (3.0 mg) decreased this reinstatement. Injections of LY379268 (3.0 mg) 1.5 mm dorsal from the NAc core into the caudate-putamen were ineffective. Results suggest an important role of glutamate transmission in the NAc shell in context-induced reinstatement of heroin seeking.

show abstract

“…It has recently been reported that group 2 mGluR-selective agonists and antagonists influence hyperlocomotor activity in rodents, after single or repeated administration of drugs of abuse. However, studies concerning their effects on drug-induced behavioral changes have been contradictory (9,10,(35)(36)(37). We addressed whether mGluR2 deficiency affects behavioral changes induced by repeated cocaine administration.…”

Section: Hyperlocomotion Under Novel Environmental and Stressful Condi-mentioning

confidence: 99%

“…Gene targeting and pharmacological studies have indicated that both ionotropic GluRs and mGluRs participate in biochemical and behavioral responses to abused drugs and psychostimulants (44). It has been reported that the group 2 mGluR-selective agonists LY379268 and LY354740 inhibit the hyperlocomotion induced by psychostimulants and psychotomimetic drugs such as amphetamine and phencyclidine (9,10). However, it has also been reported that the group 2 mGluR-selective antagonist (2S)-␣-ethylglutamic acid injected into the NAc similarly inhibit amphetamine-induced hyperlocomotion (35).…”

Section: Changes In Release Of Da and Glutamate In Mglur2 ؊͞؊ Ko Nac Bymentioning

confidence: 99%

Enhanced cocaine responsiveness and impaired motor coordination in metabotropic glutamate receptor subtype 2 knockout mice

Morishima

Miyakawa

Furuyashiki

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

145

View full text Add to dashboard Cite

Extensive pharmacological studies have recently emerged indicating that group 2 metabotropic glutamate receptors (mGluRs) comprising mGluR2 and mGluR3 subtypes are associated with several neurological and psychiatric disorders. mGluR2 is widely distributed both presynaptically and postsynaptically in a variety of neuronal cells, but the physiological role of mGluR2 in brain function is poorly understood. This investigation involves a comprehensive behavioral analysis of mGluR2 ؊͞؊ knockout (KO) mice to explore the physiological role of mGluR2 in brain function. Although, under general observation, mGluR2 ؊͞؊ KO mice appeared to have no behavioral abnormalities, they exhibited several lines of behavioral alterations in the enforcing and defined behavioral tests. They showed a significant increase in locomotor sensitization and conditioned place preference in association with repeated cocaine administration, indicating that mGluR2 contributes to behavioral responses implicated in reinforcement and addiction of cocaine. Upon in vivo microdialysis analysis after cocaine administration, not only did extracellular levels of dopamine increase but also the response pattern of glutamate release markedly changed in the nucleus accumbens of mGluR2 ؊͞؊ KO mice. The mGluR2 ؊͞؊ KO mice also showed significant impairment in motor coordination in the accelerating rota-rod test and exhibited hyperlocomotion in novel environmental and stressful conditions, when assessed by the open-field and forced-swim tests. These results indicate that the inhibitory mGluR2 plays a pivotal role in synaptic regulation of glutamatergic transmission in the neural network.addiction ͉ hyperactivity ͉ microdialysis ͉ glutamatergic transmission ͉ nucleus accumbens

show abstract

The mGlu2/3 receptor agonist LY379268 blocks the expression of locomotor sensitization by amphetamine

Cited by 52 publications

References 29 publications

Environmental enrichment increases amphetamine-induced glutamate neurotransmission in the nucleus accumbens: A neurochemical study

Environmental enrichment increases amphetamine-induced glutamate neurotransmission in the nucleus accumbens: A neurochemical study

Activation of Group II Metabotropic Glutamate Receptors in the Nucleus Accumbens Shell Attenuates Context-Induced Relapse to Heroin Seeking

Enhanced cocaine responsiveness and impaired motor coordination in metabotropic glutamate receptor subtype 2 knockout mice

Contact Info

Product

Resources

About