scholarly journals Attenuation of morphine antinociceptive tolerance by an NMDA receptor antagonist and a cannabinoid receptor agonist: interactive effects

2007 ◽  
Vol 21 (5) ◽  
Author(s):  
Bradford D Fischer ◽  
Fredrick E Henry ◽  
Laurence L Miller ◽  
Sara J Ward ◽  
Linda A Dykstra
Keyword(s):  
Nmda Receptor ◽  
Receptor Antagonist ◽  
Receptor Agonist ◽  
Cannabinoid Receptor ◽  
Nmda Receptor Antagonist ◽  
Interactive Effects ◽  
Antinociceptive Tolerance

scholarly journals Ionotropic Glutamate Receptors in Hypothalamic Paraventricular and Supraoptic Nuclei Mediate Vasopressin and Oxytocin Release in Unanesthetized Rats

Endocrinology ◽  
2012 ◽  
Vol 153 (5) ◽  
pp. 2323-2331 ◽  
Author(s):  
Cristiane Busnardo ◽  
Carlos C. Crestani ◽  
Leonardo B. M. Resstel ◽  
Rodrigo F. Tavares ◽  
José Antunes-Rodrigues ◽  
...  
Keyword(s):  
Nmda Receptor ◽  
Nmda Receptors ◽  
Receptor Antagonist ◽  
Glutamate Receptors ◽  
Plasma Levels ◽  
Receptor Agonist ◽  
Local Treatment ◽  
Nmda Receptor Antagonist ◽  
Oxytocin Release ◽  
Circulating Levels

We report changes in plasma arginine vasopressin (AVP) and oxytocin (OT) concentrations evoked by the microinjection of l-glutamate (l-glu) into the hypothalamic supraoptic nucleus (SON) and paraventricular nucleus (PVN) of unanesthetized rats, as well as which local mechanisms are involved in their mediation. l-Glu microinjection (10 nmol/100 nl) into the SON increased the circulating levels of both AVP and OT. The AVP increases were blocked by local pretreatment with the selective non-N-methyl-d-aspartate (NMDA) receptor antagonist 2,3-dioxo-6-nitro-1,2,3,4-tetrahydrobenzo[f]quinoxaline-7-sulfonamide (NBQX) (2 nmol/100 nl), but it was not affected by pretreatment with the NMDA-receptor antagonist LY235959 (2 nmol/100 nl). The OT response to l-glu microinjection into the SON was blocked by local pretreatment with either NBQX or LY235959. Furthermore, the administration of either the non-NMDA receptor agonist (±)-α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid hydrobromide (AMPA) (5 nmol/100 nl) or NMDA receptor agonist NMDA (5 nmol/100 nl) into the SON had no effect on OT baseline plasma levels, but when both agonists were microinjected together these levels were increased. l-Glu microinjection into the PVN did not change circulating levels of either AVP or OT. However, after local pretreatment with LY235959, the l-glu microinjection increased plasma levels of the hormones. The l-glu microinjection into the PVN after the local treatment with NBQX did not affect the circulating AVP and OT levels. Therefore, results suggest the AVP release from the SON is mediated by activation of non-NMDA glutamate receptors, whereas the OT release from this nucleus is mediated by an interaction of NMDA and non-NMDA receptors. The present study also suggests an inhibitory role for NMDA receptors in the PVN on the release of AVP and OT.

scholarly journals Spinal Effects of Bicuculline: Modulation of an Allodynia-Like State by an A1-Receptor Agonist, Morphine, and an NMDA-Receptor Antagonist

1998 ◽  
Vol 79 (3) ◽  
pp. 1494-1507 ◽  
Author(s):  
Alison J. Reeve ◽  
Anthony H. Dickenson ◽  
Nicola C. Kerr
Keyword(s):  
Nmda Receptor ◽  
Receptor Antagonist ◽  
Dorsal Horn ◽  
Receptor Agonist ◽  
Nmda Receptor Antagonist ◽  
Dependent Manner ◽  
Evoked Responses ◽  
C Fiber ◽  
Evoked Activity ◽  
Fiber Stimulation

Reeve, Alison J., Anthony H. Dickenson, and Nicola C. Kerr. Spinal effects of bicuculline: modulation of an allodynia-like state by an A1-receptor agonist, morphine, and an NMDA-receptor antagonist. J. Neurophysiol. 79: 1494–1507, 1998. Single-unit recordings were made in the intact anesthetized rat of the responses of dorsal horn neurons to C-, Aδ-, and Aβ-fiber stimulation. The postdischarge and windup responses of the same cells along with responses to innocuous stimuli, prod and brush, also were measured. The effects of (−)-bicuculline-methobromide (0.5, 5, 50, and 250 μg) were observed on these neuronal responses. The C- and Aδ-fiber–evoked responses were facilitated significantly in a dose-dependent manner. The input was facilitated, but as the final overall response was not increased by the same factor, windup appeared to be reduced. However, postdischarge, resulting from the increase in the excitability produced by windup, tended to be facilitated. After doses of ≥5 μg bicuculline, stimulation at suprathreshold Aβ-fiber–evoked activity caused enhanced firing, mainly at later latencies corresponding to Aδ-fiber–evoked activity in normal animals. Few cells responded consistently to brush and so no significant change was observed. Responses evoked by innocuous pressure (prod) always were observed in cells that concurrently responded to electrical stimulation with a C-fiber response. This tactile response was facilitated significantly by bicuculline. The effects of N6-cyclopentyladenosine (N6-CPA), an adenosine A1-receptor agonist, was observed after pretreatment with 50 μg bicuculline, as were the effects of morphine and 7-chlorokynurenate (7-CK). N6-CPA inhibited prod, C- and Aδ-fiber–evoked responses as well as the initial and overall final response to the train of C-fiber strength stimuli. Inhibitions were reversed with 8(p-sulphophenyl) theophylline. Morphine, the mu-receptor agonist, also inhibited the postbicuculline responses to prod, C-, and Aδ-fiber responses and initial and final responses to a train of stimuli. Inhibitory effects of morphine were reversed partly by naloxone. 7-CK, an antagonist at the glycine site on the N-methyl-d-aspartate-receptor complex, inhibited the responses to C- and Aδ-fiber–evoked activity as well as prod. The postdischarges were inhibited by this drug. Again both the initial and overall responses of the cell were inhibited. To conclude, bicuculline caused an increase in the responses of deep dorsal horn cells to prod, Aδ-fiber–evoked activity, increased C-fiber input onto these cells along with the appearance of responses at latencies normally associated with Aδ fibers, but evoked by suprathreshold Aβ-fiber stimulation. These alterations may be responsible for some aspects of the clinical phenomenon of allodynia and hyperalgesia. These altered and enhanced responses were modulated by the three separate classes of drugs, the order of effectiveness being 7-CK, N6-CPA, and then morphine.

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