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Because COC is also a potent local anesthetic, its rapid action on Na+ channels may be responsible for triggering these effects. We monitored temperatures in the nucleus accumbens, temporal muscle and skin together with conventional locomotion during a single i.v. injection of COC (1\u2003mg\/kg), procaine (PRO, 5\u2003mg\/kg; equipotential anesthetic dose), a short\u2010acting local anesthetic drug that, like COC, interacts with Na+ channels, and cocaine methiodide (COC\u2010MET, 1.31\u2003mg\/kg, equimolar dose), a quaternary COC derivative that is unable to cross the blood\u2013brain barrier. In this way, we explored not only the importance of Na+ channels in general, but also the importance of central vs. peripheral Na+ channels specifically. COC induced locomotor activation, temperature increase in the brain and muscle, and a biphasic temperature fluctuation in skin. Though PRO did not induce locomotor activation, it mimicked, to a greater degree, the temperature effects of COC. Therefore, Na+ channels appear to be a key substrate for COC\u2010induced temperature fluctuations in the brain and periphery. Similar to PRO, COC\u2010MET had minimal effects on locomotion, but mimicked COC in its ability to increase brain and muscle temperature, and induce transient skin hypothermia. It appears therefore that COC's interaction with peripherally located Na+ channels triggers its central excitatory effects manifested by brain temperature increase, thereby playing a major role in drug sensing and possibly contributing to COC reinforcement.<\/jats:p>","DOI":"10.1111\/j.1460-9568.2006.05001.x","type":"journal-article","created":{"date-parts":[[2006,8,29]],"date-time":"2006-08-29T14:50:44Z","timestamp":1156863044000},"page":"1182-1192","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["The role of peripheral Na+ channels in triggering the central excitatory effects of intravenous cocaine"],"prefix":"10.1111","volume":"24","author":[{"given":"P. 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