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Journal of Pharmacology And Experimental Therapeutics Fast Forward
First published on June 1, 2007; DOI: 10.1124/jpet.107.121137

0022-3565/07/3223-1278-1285$20.00
JPET 322:1278-1285, 2007
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NEUROPHARMACOLOGY

Modulation of Brainstem Opiate Analgesia in the Rat by {sigma}1 Receptors: A Microinjection Study

Jianfeng Mei, and Gavril W. Pasternak

The Laboratory of Molecular Neuropharmacology, Memorial Sloan-Kettering Cancer Center, New York, New York

{sigma}1 Receptors have been implicated in the modulation of opioid analgesia. In the current study, we examined the role of {sigma}1 systems in the periaqueductal gray (PAG), the rostroventral medulla (RVM), and the locus coeruleus (LC) of the rat, regions previously shown to be sensitive to morphine. Morphine was a potent analgesic in all three regions. Coadministration of the {sigma}1 agonist (+)-pentazocine diminished the analgesic actions of morphine in all three regions, although the PAG was far less sensitive than the other two regions. Blockade of the {sigma}1 receptors with haloperidol in the RVM markedly enhanced the analgesic actions of coadministered morphine, implying a tonic activity of the {sigma}1 system in this region. This effect was mimicked by down-regulation of RVM {sigma}1 receptors using an antisense approach. However, no tonic {sigma}1 activity was observed in either the LC or the PAG. The RVM also was important in modulating analgesia elicited from morphine microinjected into the PAG. The analgesic actions of morphine given into the PAG could be attenuated by (+)-pentazocine placed into the RVM, whereas haloperidol in the RVM enhanced PAG morphine analgesia. These studies illustrate the pharmacological importance of {sigma}1 receptors in the brainstem modulation of opioid analgesia.

Received February 9, 2007; accepted May 31, 2007.

Address correspondence to: Dr. Gavril W. Pasternak, Department of Neurology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 1002. E-mail: pasterng{at}mskmail.mskcc.org






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