Modulation of glutamate release by a κ-opioid receptor agonist in rodent and primate striatum

doi:10.1016/0014-2999(95)00385-X

European Journal of Pharmacology

Volume 281, Issue 1, 25 July 1995, Pages R1-R2

https://doi.org/10.1016/0014-2999(95)00385-X Get rights and content

Abstract

The influence of the κ-opioid receptor agonist, enadoline, on endogenous glutamate release was investigated in rat and marmoset striatal synaptosomes. Enadoline decreased 4-aminopyridine (2 mM)-stimulated glutamate release (rat: IC₅₀ ∼ 8.7 μM, marmoset: IC₅₀ ∼ 2.9 μM). The effect of enadoline was reversed by nor-binaltorphimine (5 μM). These data indicate that, in the striatum of the rat and marmoset, κ-opioid receptor agonists can modulate glutamate release. These findings may have implications for the treatment of Parkinson's disease.

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Our results showed that a single morphine injection decreased the levels of p-GluN2B (Ser 1303) while the total GluN2B was unchanged in each brain region. Research has shown that opioid receptor agonists inhibit the release of glutamate in the striatum and cortex [26,27]. Furthermore, Liu et al. has reported that p-GluNR2B (Ser 1303) decreases in the striatum 30 min after acute cocaine administration without affecting the total GluN2B, which they attribute to dopamine D2 receptors that interfere with the interaction between GluN2B and CaMKII [28].
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Dorsal hippocampal N-methyl-d-aspartate glutamatergic and δ-opioidergic systems modulate anxiety behaviors in rats in a noninteractive manner
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Although the δ-opioid receptor knockout mice showed anxiogenic-like responses in the elevated plus maze (EPM) and the light-dark box, the mice lacking μ-opioid receptors showed lower levels of anxiety in the EPM [8]. Interactions between opioidergic and glutamatergic systems are reported in the different areas of the brain, such as sensorimotor cortex [9], striatum [10], dorsal raphe nucleus [11], and finally in spinal cord [12]. Opioids inhibit glutamate release in rat periaqueductal gray cells, CA3 area [13], and also in the CA1 region of the hippocampus [12].
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Non-human primate (NHP) models of Parkinson’s disease (PD) have been essential in understanding the pathophysiology and neural mechanisms underlying PD. The most common toxin employed, MPTP, produces a parkinsonian phenotype in NHPs that is very similar to human PD with excellent response to dopaminergic drugs and development of long-term motor complications. Over the past 25 years, MPTP-lesioned NHP models, using several species and a variety of MPTP administration regimens, have been used to understand disease pathophysiology, investigate several stages of the disease progression, from pre-symptomatic to advanced with motor complications, and apply knowledge gained to develop potential therapeutics. Many treatments in common use in PD patients were developed on the basis of studies in the MPTP model, in particular dopamine agonists, amantadine, and targeting the subthalamic nucleus for surgical treatment of PD. Continued development of novel therapies for PD will require improving methods of evaluating symptoms in NHPs to ease translation from NHP to patients with homogenized scales and endpoints. In addition, recent studies into non-motor symptoms of PD, especially in response to chronic treatment, is expanding the usefulness and impact of MPTP-lesioned NHP models. Despite these obvious successes, limitations still exist in the model, particularly when considering underlying mechanisms of disease progression; thus, it appears difficult to reliably use acute toxin administration to replicate a chronic progressive disorder and provide consistent evidence of Lewy-like bodies.
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The mechanisms by which kappa agonists exert protective effects against ischemic damage are suggested by a number of previous studies. For example, in vitro, kappa agonists have been shown to inhibit the release of glutamate by blocking calcium entry into presynaptic terminals [33,34]. Consistent with such findings, significant inhibition of glutamate release following focal ischemia in animals pretreated with the kappa agonist CI-977 was observed [35].
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Rapid communicationModulation of glutamate release by a κ-opioid receptor agonist in rodent and primate striatum

Abstract

Eur. J. Pharmacol.

Brain Res.

Brain Res.

Neurochemical and behavioural investigations of the NMDA-associated glycine site in the rat striatum: functional implications for the treatment of parkinsonian symptoms

Psychopharmacology

Rapid communication
Modulation of glutamate release by a κ-opioid receptor agonist in rodent and primate striatum