Neuroscience 2005 Abstract
| Presentation Number: | 802.8 |
|---|---|
| Abstract Title: | Differential effects of chronic morphine and methadone administrations on μ-opioid and cannabinoid CB1 receptor activation of G-proteins in specific rat brain nuclei. |
| Authors: |
Llorente, J.*1
; Pineda, J.1
; Rodriguez-Puertas, R.1
1Dept. of Pharmacology, Faculty of Medicine, Univ. of the Basque Country, Leioa (Bizkaia), Spain |
| Primary Theme and Topics |
Disorders of the Nervous System - Addiction and Drugs of Abuse -- Opioids |
| Secondary Theme and Topics | Neural Excitability, Synapses, and Glia: Cellular Mechanisms<br />- G-Protein Linked Receptors<br />-- Opioid receptors |
| Session: |
802. Drugs of Abuse: Opioids III Poster |
| Presentation Time: | Tuesday, November 15, 2005 4:00 PM-5:00 PM |
| Location: | Washington Convention Center - Hall A-C, Board # WW33 |
| Keywords: | OPIATE, DESENSITIZATION, AUTORADIOGRAPHY, LOCUS COERULEUS |
Chronic administration of opioid agonists decreases µ opioid receptor (MOR)-activated G proteins in different brainstem nuclei. The prototypic MOR agonist morphine differs from other opioid agonists in its ability to induce strong analgesic tolerance but weak receptor internalization. On the other hand, a close relation between opioid and cannabinoid systems has been reported, including the inhibition of analgesic and rewarding effects of Δ9-THC by the MOR antagonist naloxone. Therefore, we investigated the effect of morphine or methadone treatments on MOR- and cannabinoid CB1 receptor-coupled G protein activation as measured by the [35S]GTPγS autoradiography technique.
Chronic administration of morphine by a subcutaneous pellet (200 mg/kg, 3 days) induced desensitization to DAMGO (MOR agonist)-stimulated G protein activation in nucleus accumbens, amygdaloid nuclei, lateral parabrachial nucleus and locus coeruleus. Chronic methadone treatment (5–7.5 mg/kg, 5 days) induced desensitization to MOR activation of G proteins in the locus coeruleus but also in other different regions such as periaqueductal gray, substantia nigra pars compacta and ventral tegmental area. No change was observed for WIN 55,212-2 (CB1 receptor agonist)-stimulated G protein activation in these areas. Paradoxically, in regions such as nucleus accumbens, caudate-putamen, amygdaloid nuclei, mediodorsal thalamic nucleus and substantia nigra pars reticulata, methadone desensitized CB1 receptor-coupled G protein activation, but not MOR-coupled signalling.
The present results suggest that chronic morphine and methadone treatments induce differentially a region-dependent desensitization of µ opioid receptors and that methadone induces a heterologous CB1 receptor desensitization in those regions where the µ opioid receptor signalling is preserved.
Chronic administration of morphine by a subcutaneous pellet (200 mg/kg, 3 days) induced desensitization to DAMGO (MOR agonist)-stimulated G protein activation in nucleus accumbens, amygdaloid nuclei, lateral parabrachial nucleus and locus coeruleus. Chronic methadone treatment (5–7.5 mg/kg, 5 days) induced desensitization to MOR activation of G proteins in the locus coeruleus but also in other different regions such as periaqueductal gray, substantia nigra pars compacta and ventral tegmental area. No change was observed for WIN 55,212-2 (CB1 receptor agonist)-stimulated G protein activation in these areas. Paradoxically, in regions such as nucleus accumbens, caudate-putamen, amygdaloid nuclei, mediodorsal thalamic nucleus and substantia nigra pars reticulata, methadone desensitized CB1 receptor-coupled G protein activation, but not MOR-coupled signalling.
The present results suggest that chronic morphine and methadone treatments induce differentially a region-dependent desensitization of µ opioid receptors and that methadone induces a heterologous CB1 receptor desensitization in those regions where the µ opioid receptor signalling is preserved.
Supported by Grants SAF-2001/0552, and FIS RTA G03/005. J.L. is a fellow from the MCT
Sample Citation:
[Authors]. [Abstract Title]. Program No. XXX.XX. 2005 Neuroscience Meeting Planner. Washington, DC: Society for Neuroscience, 2005. Online.
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