The involvement of the mu-opioid receptor in ketamine-induced respiratory depression and antinociception

Citation
E. Sarton et al., The involvement of the mu-opioid receptor in ketamine-induced respiratory depression and antinociception, ANESTH ANAL, 93(6), 2001, pp. 1495-1500
Citations number
27
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Aneshtesia & Intensive Care","Medical Research Diagnosis & Treatment
Journal title
ANESTHESIA AND ANALGESIA
ISSN journal
0003-2999 → ACNP
Volume
93
Issue
6
Year of publication
2001
Pages
1495 - 1500
Database
ISI
SICI code
0003-2999(200112)93:6<1495:TIOTMR>2.0.ZU;2-I
Abstract
N-methyl-D-aspartate receptor antagonism probably accounts for most of keta mine's anesthetic effects; its analgesic properties are mediated partly via N-methyl-D-aspartate and partly via opioid receptors. We assessed the invo lvement of the mu -opioid receptor in S(+) ketamine-induced respiratory dep ression and antinociception by performing dose-response curves in exon 2 bt -opioid receptor knockout mice (MOR-/-) and their wild-type littermates (WT ). The ventilatory response to increases in inspired CO2 was measured with whole body plethysmography. Two antinociceptive assays were used: the tail- immersion test and the hotplate test. S(+) ketamine (0, 10, 100, and 200 mg /kg intraperitoneally) caused a dose-dependent respiratory depression in bo th genotypes, with greater depression observed in WT relative to MOR-/- mic e. At 200 mg/kg, S(+) ketamine reduced the slope of the hypercapnic ventila tory response by 93% +/- 15% and 49% +/- 6% in WT and MOR-/- mice, respecti vely (P < 0.001). In both genotypes, S(+) ketamine produced a dose-dependen t increase in latencies in the hotplate test, with latencies in MOR-/- mice smaller compared with those in WT animals (P < 0.05). In contrast to WT mi ce, MOR-/- mice displayed no ketamine-induced antinociception in the tail-i mmersion test. These results indicate that at supraspinal sites S(+) ketami ne interacts with the ti-opioid system. This interaction contributes signif icantly to S(+) ketamine-induced respiratory depression and supraspinal ant inociception.