Modulation of NMDA- and (+)TAN-67-induced nociception by GABA(B) receptors in the mouse spinal cord.

Abstract

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.

• Authors: Y Yajima, M Narita, M Tsuda, S Imai, J Kamei, H Nagase, T Suzuki
• Journal: Life sciences (Life Sci) Vol. 68 Issue 6 Pg. 719-25 (Dec 29 2000) ISSN: 0024-3205 [Print] Netherlands
• PMID: 11205886 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Analgesics
• Excitatory Amino Acid Agonists
• Excitatory Amino Acid Antagonists
• GABA Agonists
• Quinolines
• Receptors, GABA-B
• TAN 67
• N-Methylaspartate
• Dizocilpine Maleate
• Baclofen

Topics

• Analgesics (pharmacology)
• Animals
• Baclofen (pharmacology)
• Dizocilpine Maleate (pharmacology)
• Dose-Response Relationship, Drug
• Excitatory Amino Acid Agonists (pharmacology)
• Excitatory Amino Acid Antagonists (pharmacology)
• GABA Agonists (pharmacology)
• Injections, Spinal
• Male
• Mice
• N-Methylaspartate (antagonists & inhibitors, pharmacology)
• Pain (chemically induced)
• Quinolines (antagonists & inhibitors, pharmacology)
• Receptors, GABA-B (drug effects)
• Spinal Cord (drug effects)