Modulation of NMDA- and (+)TAN-67-induced nociception by GABA(B) receptors in the mouse spinal cord.
The present study was designed to investigate the effect of a selective GABA(B) receptor agonist baclofen on the pain-like nociceptive behavior (scratching, biting and licking) induced by intrathecal (i.t.) injection of N-methyl-D-aspartate (NMDA) or (+)TAN-67, the enantiomorphs of 2-methyl-4aalpha-(3-hydroxyphenyl)-1,2,3,4,4a,5,12,12aalpha-octahydro-quinolino[2,3,3g]isoquinoline (TAN-67), in the mouse. NMDA (0.05-0.2 microg/mouse) given i.t. immediately caused nociception in a dose-dependent manner. The nociception was significantly antagonized by i.t. co-injection with dizocilipine (0.1-1.0 microg/mouse), a non-competitive NMDA receptor antagonist. I.t. co-injection with baclofen (37.5-150 ng/mouse) significantly reduced the NMDA-induced nociceptive behavior in a dose-dependent fashion. The inhibition produced by baclofen was completely reversed by a selective GABA(B) receptor antagonist 2-hydroxysaclofen (0.15 and 0.3 microg/mouse). An i.t. injection of (+)TAN-67 at doses of 3.75-15 microg/mouse elicited a long-lasting and a dose-related nociception. The nociceptive behavior induced by (+)TAN-67 given i.t. was markedly suppressed by i.t. co-injection with baclofen (3-30 ng/mouse), and the inhibitory effect of baclofen was prevented by i.t. injection of 2-hydroxysaclofen (1 and 3 microg/ mouse). In addition, the (+)TAN-67-induced nociception was also attenuated by i.t. co-injection with dizocilipine (0.1-1.0 microg/mouse). These results suggest that spinal GABA(B) receptors may be implicated in the expression of nociception elicited by i.t. injection of either NMDA or (+)TAN-67 in the mouse.
Yajima
Y
Y
Department of Toxicology, School of Pharmacy, Hoshi University, Tokyo, Japan.
Narita
M
M
Tsuda
M
M
Imai
S
S
Kamei
J
J
Nagase
H
H
Suzuki
T
T
D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018755:GABA Agonists / Q000494:pharmacology; D007278:Injections, Spinal; D008297:Male; D051379:Mice; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D010146:Pain / Q000139:chemically induced*; D011804:Quinolines / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D018080:Receptors, GABA-B / Q000187:drug effects*; D013116:Spinal Cord / Q000187:drug effects*
D000700:Analgesics; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D018755:GABA Agonists; D011804:Quinolines; D018080:Receptors, GABA-B; C094142:TAN 67; D016202:N-Methylaspartate; D016291:Dizocilpine Maleate; D001418:Baclofen