(+)-Morphine and (-)-morphine stereoselectively attenuate the (-)-morphine-produced tail-flick inhibition via the naloxone-sensitive sigma receptor in the ventral periaqueductal gray of the rat. Eur J Pharmacol 2007 Sep 24;571(1):1-7
Date
06/29/2007Pubmed ID
17597599Pubmed Central ID
PMC3718891DOI
10.1016/j.ejphar.2007.05.033Scopus ID
2-s2.0-34548044285 (requires institutional sign-in at Scopus site) 12 CitationsAbstract
We have previously demonstrated that (+)-morphine and (-)-morphine pretreated spinally for 45 min stereoselectively attenuates the tail-flick inhibition produced by (-)-morphine given spinally in the mouse. The present study is then undertaken to determine if the same phenomenon observed in the mouse spinal cord can also take place in the ventral periaqueductal gray of the rat. Pretreatment with (+)-morphine for 45 min at 0.3 to 3.3 fmol dose-dependently attenuated the tail-flick inhibition produced by (-)-morphine (9 nmol) given into the ventral periaqueductal gray. Likewise, pretreatment with (-)-morphine for 45 min at a higher dose (3-900 pmol), which given alone did not affect the baseline tail-flick latency, also dose-dependently attenuated the tail-flick inhibition produced by (-)-morphine. Thus, (+)-morphine is approximately 270,000-fold more potent than (-)-morphine in attenuating the (-)-morphine-produced tail-flick inhibition. The attenuation of the (-)-morphine-produced tail-flick inhibition induced by (+)-morphine or (-)-morphine was dose-dependently reversed by (+)-naloxone (27.5 to 110 pmol) pretreatment for 50 min given into the ventral periaqueductal gray. Pretreatment with the sigma receptor antagonist BD1047 (N-[2-(3,4-dichlorophenyl)ethyl]-N-methyl-2-(dimethylamino)ethylamine dihydrobromide) (11-45 nmol) for 45 min given into the ventral periaqueductal gray also reversed dose-dependently the attenuation of the (-)-morphine-produced tail-flick inhibition induced by (+)-morphine or (-)-morphine, indicating that the effects are mediated by the activation of the sigma receptors. Since (+)-morphine, (-)-morphine and (+)-naloxone do not have any affinity for the naloxone-inaccessible sigma receptors, we therefore propose that (+)-morphine and (-)-morphine attenuate the (-)-morphine-produced tail-flick inhibition via the activation of the naloxone-sensitive sigma receptor originally proposed by Tsao and Su [Tsao, L.T., Su, T.P., 1997. Naloxone-sensitive, haloperidol-sensitive, [(3)H](+)-SKF-1047-binding protein partially purified from rat liver and rat brain membranes: an opioid/sigma receptor. Synapse 25, 117-124].
Author List
Terashvili M, Wu HE, Moore RM, Harder DR, Tseng LFMESH terms used to index this publication - Major topics in bold
Analgesics, OpioidAnimals
Dose-Response Relationship, Drug
Ethylenediamines
Male
Microinjections
Models, Anatomic
Morphine
Naloxone
Narcotic Antagonists
Pain
Pain Measurement
Periaqueductal Gray
Rats
Receptors, sigma
Stereoisomerism
Tail
Time Factors
