Free
Correspondence  |   June 2003
Is Attenuation of Extracellular Dopamine Increase in the Nucleus Accumbens the Major Mechanism by which Dexmedetomidine Increases the Cocaine Seizure Threshold in Rats?
Author Notes
  • Department of Anesthesiology, Kansai Medical University, Osaka, Japan.
Article Information
Correspondence
Correspondence   |   June 2003
Is Attenuation of Extracellular Dopamine Increase in the Nucleus Accumbens the Major Mechanism by which Dexmedetomidine Increases the Cocaine Seizure Threshold in Rats?
Anesthesiology 6 2003, Vol.98, 1520. doi:
Anesthesiology 6 2003, Vol.98, 1520. doi:
To the Editor:—
I am very impressed with the recent article by Whittington et al.  , which demonstrated that dexmedetomidine increased the cocaine-induced seizure threshold via  the attenuation of the cocaine-induced increase in extracellular dopamine concentration in the rat nucleus accumbens. 1 It is true that the increase in extracellular dopamine concentration in the nucleus accumbens may be closely related to the cocaine-induced seizure activity because cocaine inhibits dopamine transporters, but recent studies have suggested that ς receptors, which are endoplasmic reticulum protein and directly activated by cocaine, are more likely involved in the cocaine-induced seizure activity than the dopamine transporters. 2 On the other hand, we have recently demonstrated that ketamine, which has anticonvulsant and also proconvulsant properties, markedly increases dopamine release in the nucleus accumbens. 3 Ketamine affected the ς receptors 4 and ketamine-induced c-fos protein expression in the posterior cingulate and retrosplenial cortices, which might be a reliable indicator of ketamine-induced psychotomimetic activity, was mediated at least partly via  the ς receptors. 5 Therefore, I wonder whether the cocaine-induced increase in extracellular dopamine concentration in the nucleus accumbens is the major mechanism by which cocaine induces seizures and furthermore the ς receptors may be involved in the inhibitory effects of dexmedetomidine on the cocaine-induced seizures.
References
Whittington RA, Virag L, Vulliemoz Y, Cooper TB, Morishima HO: Dexmedetomidine increases the cocaine seizure threshold in rats. A nesthesiology 2002; 97: 693–700Whittington, RA Virag, L Vulliemoz, Y Cooper, TB Morishima, HO
Matsumoto RR, Hewett KL, Pouw B, Bowen WD, Husbands SM, Cao JJ, Hauck Newman A: Rimcazole analogs attenuate the convulsive effects of cocaine: Correlation with binding to sigma receptors rather than dopamine transporters. Neuropharmacology 2001; 41: 878–86Matsumoto, RR Hewett, KL Pouw, B Bowen, WD Husbands, SM Cao, JJ Hauck Newman, A
Masuzawa M, Nakao S, Miyamoto E, Yamada M, Murao K, Nishi K, Shingu K: Pentobarbital inhibits ketamine-induced dopamine release in the rat nucleus accumbens: A microdialysis study. Anesth Analg 2003; 96: 148–52Masuzawa, M Nakao, S Miyamoto, E Yamada, M Murao, K Nishi, K Shingu, K
Hustveit O, Maurset A, Oye I: Interaction of chiral forms of ketamine with opioids, phencyclidine, sigma and muscarinic receptor. Pharmacol Toxicol 1995; 77: 355–9Hustveit, O Maurset, A Oye, I
Nakao S, Miyamoto E, Masuzawa M, Kambara T, Shingu K: Ketamine-induced c-Fos expression in the mice posterior cingulate and retrosplenial cortices are mediated not only via NMDA receptors but also via sigma receptors. Bain Res 2002; 926: 191–6Nakao, S Miyamoto, E Masuzawa, M Kambara, T Shingu, K