TY - JOUR T1 - Modulation of Brainstem Opiate Analgesia in the Rat by σ<sub>1</sub> Receptors: A Microinjection Study JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 1278 LP - 1285 DO - 10.1124/jpet.107.121137 VL - 322 IS - 3 AU - Jianfeng Mei AU - Gavril W. Pasternak Y1 - 2007/09/01 UR - http://jpet.aspetjournals.org/content/322/3/1278.abstract N2 - σ1 Receptors have been implicated in the modulation of opioid analgesia. In the current study, we examined the role of σ1 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 σ1 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 σ1 receptors with haloperidol in the RVM markedly enhanced the analgesic actions of coadministered morphine, implying a tonic activity of the σ1 system in this region. This effect was mimicked by down-regulation of RVM σ1 receptors using an antisense approach. However, no tonic σ1 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 σ1 receptors in the brainstem modulation of opioid analgesia. ER -