The effects of local perfusion of DAMGO on extracellular GABA and glutamate concentrations in the rostral ventromedial medulla

Schepers, Raf; Mahoney, Janet Lynn; Zapata, Agustín; Chefer, Vladimir I.; Shippenberg, Toni S.

doi:10.1111/j.1471-4159.2007.05017.x

Cited by 14 publications

(15 citation statements)

References 64 publications

(149 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Similar findings have been obtained in vitro in tissue obtained from patients with temporal lobe epilepsy [36]. It has been demonstrated that under basal conditions the uptake of glutamate from the extracellular space is very rapid, however when uptake transport is inhibited by tPDC then changes in glutamate release can be unmasked [28]. Collectively, these results indicate that depolarization-dependent release of glutamate is enhanced as a consequence of seizure kindling with cocaine.…”

Section: Discussionsupporting

confidence: 80%

“…1a). Rapid transporter-mediated uptake may mask the detection of changes in glutamate release [28], therefore a selective excitatory amino acid transporter inhibitor tPDC [26] was added to the perfusion medium for subsequent studies. tPDC caused significant (approximately fivefold) increase of glutamate levels in both kindled and control mice ( P < 0.05) (Fig.…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Effects of Cocaine-Kindling on the Expression of NMDA Receptors and Glutamate Levels in Mouse Brain

et al. 2010

Self Cite

View full text Add to dashboard Cite

In the present study we examined the effects of cocaine seizure kindling on the expression of NMDA receptors and levels of extracellular glutamate in mouse brain. Quantitative autoradiography did not reveal any changes in binding of [3H] MK-801 to NMDA receptors in several brain regions. Likewise, in situ hybridization and Western blotting revealed no alteration in expression of the NMDA receptor subunits, NR1 and NR2B. Basal overflow of glutamate in the ventral hippocampus determined by microdialysis in freely moving animals also did not differ between cocaine-kindled and control groups. Perfusion with the selective excitatory amino acid transporter inhibitor, pyrrolidine-2,4-dicarboxylic acid (tPDC, 0.6 mM), increased glutamate overflow confirming transport inhibition. Importantly, KCl-evoked glutamate overflow under tPDC perfusion was significantly higher in cocaine-kindled mice than in control mice. These data suggest that enhancement of depolarization stimulated glutamate release may be one of the mechanisms underlying the development of increased seizure susceptibility after cocaine kindling.

show abstract

Section: Discussionsupporting

confidence: 80%

Section: Resultsmentioning

confidence: 99%

Effects of Cocaine-Kindling on the Expression of NMDA Receptors and Glutamate Levels in Mouse Brain

et al. 2010

Self Cite

View full text Add to dashboard Cite

show abstract

“…Often, increases in dialysate glutamate levels can be seen only when its uptake is blocked. Thus, in a recent paper, Schepers et al. (2008) showed that infusion of DAMGO increased glutamate concentrations in the rostral ventromedial medulla only in the presence of the selective glutamate transport inhibitor tPDC.…”

Section: Discussionmentioning

confidence: 97%

Mu opioid receptor modulation of somatodendritic dopamine overflow: GABAergic and glutamatergic mechanisms

Chefer

Denoroy

Zapata

et al. 2009

Eur J of Neuroscience

View full text Add to dashboard Cite

Mu opioid receptor (MOR) regulation of somatodendritic dopamine neurotransmission in the ventral tegmental area (VTA) was investigated using conventional microdialysis in freely moving rats and mice. Reverse dialysis of the MOR agonist, DAMGO (50, 100 μM), into the VTA of rats produced a concentration-dependent increase in dialysate DA concentrations. Basal dopamine overflow in the VTA was unaltered in mice lacking the MOR gene. However, basal GABA overflow in these animals was significantly increased, while glutamate overflow was decreased. Intra-VTA perfusion of DAMGO to wildtype (WT) mice increased dopamine overflow. GABA concentrations were decreased whereas glutamate concentrations in the VTA were unaltered. Consistent with the loss of MOR, no effect of DAMGO was observed in MOR knockout (KO) mice.These data provide the first direct demonstration of tonically active MOR systems in the VTA that regulate basal glutamatergic and GABAergic neurotransmission in this region. We hypothesize that increased GABAergic neurotransmission following constitutive deletion of MOR is due to the elimination of a tonic inhibitory influence of MOR on GABA neurons in the VTA, whereas decreased glutamatergic neurotransmission in MOR KO mice is a consequence of intensified GABA tone on glutamatergic neurons and/or terminals. As a consequence, somatodendritic dopamine release is unaltered. Furthermore, MOR KO exhibit no positive correlation between basal dopamine levels and the glutamate/GABA ratio observed in WT animals.Together our findings indicate a critical role of VTA MOR in maintaining an intricate balance between excitatory and inhibitory inputs to dopaminergic neurons.

show abstract

“…In a previous study, intra-RVM infusion of DAMGO significantly decreased extracellular GABA concentration and increased PWL (Schepers et al, 2008b). These data suggest that EA may induce the release of endogenous endomorphin to activate μ opioid receptors in GABAnergic neurons and to suppress the release of GABA.…”

Section: Discussionmentioning

confidence: 75%

Rostral ventromedial medulla μ, but not κ, opioid receptors are involved in electroacupuncture anti-hyperalgesia in an inflammatory pain rat model

Li¹,

Lao²,

Xin³

et al. 2011

Brain Research

View full text Add to dashboard Cite

It has been reported that intracerebroventricular injection of a μ receptor antagonist blocked 2 but not 100 Hz electroacupuncture (EA)-produced analgesia in an uninjured animal model. Because persistent pain changes neural response to external stimulation, we hypothesized that the mechanisms of EA anti-hyperalgesia may be different in persistent pain than in health. Hyperalgesia, decreased paw withdrawal latency (PWL) to a noxious thermal stimulus, was induced by subcutaneously injecting complete Freund’s adjuvant (CFA) into the hind paws of rats. Selective antagonists against μ (CTOP: D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-ThrNH2, 6.25 nmol) and κ (Nor-BIN: nor-binaltorphimine, 10 nmol) opioid receptors were infused into the rostral ventromedial medulla (RVM) 10 min before 30-min EA treatment at acupoint Huanti (GB30) 1 hr 30 min post-CFA. PWL was measured before and 2.5 post-CFA. Both 10 Hz and 100 Hz EA-produced anti-hyperalgesia were blocked by intra-RVM μ, but not κ, receptor antagonists. Double immunofluorescence staining demonstrated that μ receptor-containing neurons were GABAnergic and that GABAa receptor-containing neurons were serotonergic in the RVM. The results demonstrated an involvement of RVM μ, but not κ, receptors in EA-produced anti-hyperalgesia. In summary, EA may induce release of endogenous endomorphins that activate μ opioid receptors in GABAnergic neurons to suppress the release of GABA. This removes the tonic inhibition of GABA on serotonergic neurons in the RVM, and activation of these serotonergic neurons inhibits pain. EA may be used as complementary treatment for inflammatory pain.

show abstract

The effects of local perfusion of DAMGO on extracellular GABA and glutamate concentrations in the rostral ventromedial medulla

Cited by 14 publications

References 64 publications

Effects of Cocaine-Kindling on the Expression of NMDA Receptors and Glutamate Levels in Mouse Brain

Effects of Cocaine-Kindling on the Expression of NMDA Receptors and Glutamate Levels in Mouse Brain

Mu opioid receptor modulation of somatodendritic dopamine overflow: GABAergic and glutamatergic mechanisms

Rostral ventromedial medulla μ, but not κ, opioid receptors are involved in electroacupuncture anti-hyperalgesia in an inflammatory pain rat model

Contact Info

Product

Resources

About