Description:
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<jats:list-item><jats:p>Intrathecal (i.t.) injection of nociceptin at small doses (fmol order) elicited a behavioural response consisting of scratching, biting and licking in conscious mice. Here we have examined the involvement of substance P‐containing neurons by using i.t. injection of tachykinin neurokinin (NK)<jats:sub>1</jats:sub> receptor antagonists and substance P (SP) antiserum.</jats:p></jats:list-item>
<jats:list-item><jats:p>Nociceptin‐induced behavioural response was evoked significantly 5–10 min after i.t. injection and reached a maximum at 10–15 min. Dose‐dependency of the induced response showed a bell‐shaped pattern from 0.375–30.0 fmol, and the maximum effect was observed at 3.0 fmol.</jats:p></jats:list-item>
<jats:list-item><jats:p>The behavioural response elicited by nociceptin (3.0 fmol) was dose‐dependently inhibited by intraperitoneal (i.p.) administration of morphine.</jats:p></jats:list-item>
<jats:list-item><jats:p>The NK<jats:sub>1</jats:sub> receptor antagonists, CP‐96,345, CP‐99,994 and sendide, inhibited nociceptin‐induced behavioural response in a dose‐dependent manner. A significant antagonistic effect of [<jats:sc>D</jats:sc>‐Phe<jats:sup>7</jats:sup>, <jats:sc>D</jats:sc>‐His<jats:sup>9</jats:sup>]SP (6–11), a selective antagonist for SP receptors, was observed against nociceptin‐induced response. The NK<jats:sub>2</jats:sub> receptor antagonist, MEN‐10376, had no effect on the response elicited by nociceptin.</jats:p></jats:list-item>
<jats:list-item><jats:p>Pretreatment with SP antiserum resulted in a significant reduction of the response to nociceptin. No significant reduction of nociceptin‐induced response was detected in mice pretreated with NKA antiserum.</jats:p></jats:list-item>
<jats:list-item><jats:p>The N‐methyl‐<jats:sc>D</jats:sc>‐aspartate (NMDA) receptor antagonists, dizocilpine (MK‐801) and <jats:sc>D</jats:sc>(−)‐2‐amino‐5‐phosphonovaleric acid (APV) (<jats:sc>D</jats:sc>‐APV), and <jats:sc>L</jats:sc>‐N<jats:sup>G</jats:sup>‐nitro arginine methyl ester (<jats:sc>L</jats:sc>‐NAME), a nitric oxide (NO) synthase inhibitor, failed to inhibit nociceptin‐induced behavioural response.</jats:p></jats:list-item>
<jats:list-item><jats:p>The present results suggest that SP‐containing neurons in the mouse spinal cord may be involved in elicitation of scratching, biting and licking behaviour following i.t. injection of nociceptin.</jats:p></jats:list-item>
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</jats:p><jats:p><jats:italic>British Journal of Pharmacology</jats:italic> (1999) <jats:bold>127</jats:bold>, 1712–1718; doi:<jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" xlink:href="10.1038/sj.bjp.0702698">10.1038/sj.bjp.0702698</jats:ext-link></jats:p>