Antisense oligodeoxynucleotides to the kappa-1 receptor block the antinociceptive effects of delta 9-THC in the spinal cord.
Intrathecal pretreatment of mice with an antisense oligodeoxynucleotide directed against the kappa-1 receptor significantly reduced the antinociceptive effects of the kappa receptor agonist U50,488 as well as delta 9-THC, the major psychoactive ingredient found in cannabis. A mismatched oligodeoxynucleotide which contained four switched bases did not block the antinociception produced by U50,488 or delta 9-THC. Furthermore, kappa-1 antisense did not alter the antinociceptive effects of either the mu receptor-selective opioid DAMGO, or the delta receptor-selective opioid DPDPE. By using kappa-1 antisense, we were able to demonstrate that an interaction occurs between the cannabinoids and opioids in the spinal cord.
Pugh
G
G
Department of Pharmacology and Toxicology, Medical College of Virginia/Virginia Commonwealth University, Richmond 23298-0613, USA.
Abood
M E
ME
Welch
S P
SP
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D000700:Analgesics / Q000037:antagonists & inhibitors*; D000818:Animals; D001483:Base Sequence; D013759:Dronabinol / Q000037:antagonists & inhibitors*; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D020881:Enkephalin, D-Penicillamine (2,5)-; D004745:Enkephalins / Q000494:pharmacology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008969:Molecular Sequence Data; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D010146:Pain / Q000503:physiopathology*; D011619:Psychotropic Drugs / Q000037:antagonists & inhibitors*; D011759:Pyrrolidines / Q000037:antagonists & inhibitors; D017473:Receptors, Opioid, kappa / Q000187:drug effects*; D013116:Spinal Cord / Q000187:drug effects*
D000700:Analgesics; D004745:Enkephalins; D016376:Oligonucleotides, Antisense; D011619:Psychotropic Drugs; D011759:Pyrrolidines; D017473:Receptors, Opioid, kappa; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D013759:Dronabinol; D020881:Enkephalin, D-Penicillamine (2,5)-