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

Yoshinori Yajima, Minoru Narita, Makoto Tsuda, Satoshi Imai, Junzo Kamei, Hiroshi Nagase, Tsutomu Suzuki

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12 Citations (Scopus)

Abstract

The present study was designed to investigate the effect of a selective GABAB 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-4aα-(3-hydroxyphenyl)-1,2,3,4,4a,5,12,12aα-octahydro-qui nolino[2,3,3g]isoquinoline (TAN-67), in the mouse. NMDA (0.05-0.2 μg/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 μg/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 GABAB receptor antagonist 2-hydroxysaclofen (0.15 and 0.3 μg/mouse). An i.t. injection of (+)TAN-67 at doses of 3.75-15 μg/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 μg/mouse). In addition, the (+)TAN-67-induced nociception was also attenuated by i.t. co-injection with dizocilipine (0.1-1.0 μg/mouse). These results suggest that spinal GABAB receptors may be implicated in the expression of nociception elicited by i.t. injection of either NMDA or (+)TAN-67 in the mouse.

Original languageEnglish
Pages (from-to)719-725
Number of pages7
JournalLife Sciences
Volume68
Issue number6
DOIs
Publication statusPublished - Dec 29 2000
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

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