Supersensitivity of sigma receptors after repeated administration of cocaine. |
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Authors: | H Ujike K Tsuchida K Akiyama S Otsuki |
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Institution: | Department of Neuropsychiatry, Okayama University Medical School, Japan. |
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Abstract: | We investigated the role of sigma receptors in the expression of behavioral sensitization induced by cocaine. Rats received intraperitoneal injections of either 20 mg/kg cocaine or saline once daily for 14 consecutive days. Cocaine-treated rats became sensitized. After a 5-day abstinence period, a challenge dose of (+)-3-3-hydroxyphenyl]-N-(1-propyl)piperidine ((+)-3-PPP), a sigma receptor agonist, was administered. (+)-3-PPP at doses of 12 and 24 mg/kg induced significantly more frequent rearing and more potent stereotypy consisting of repetitive head movement and sniffing in cocaine-sensitized rats than in saline-pretreated rats. These enhanced responses to (+)-3-PPP lasted for at least a month. The enhanced responses to (+)-3-PPP were attenuated by 30 mg/kg BMY 14802, a putative sigma antagonist, and also attenuated by 100 mg/kg (+/-)-sulpiride, a D2 dopamine antagonist. These findings show that repeated administration of cocaine produces lasting supersensitivity of simga receptors, which may induce subsequent activation of dopaminergic transmission. |
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