Journal
NEUROSCIENCE LETTERS
Volume 484, Issue 2, Pages 113-117Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.neulet.2010.08.027
Keywords
Methamphetamine; Dependence; Withdrawal; Planarian; Serotonin; 5-HT1A
Categories
Funding
- National Institutes on Drug Abuse [DA022694]
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No pharmacological therapy is approved to treat methamphetamine physical dependence, but it has been hypothesized that serotonin (5-HT)-enhancing drugs might limit the severity of withdrawal symptoms. To test this hypothesis, we used a planarian model of physical dependence that quantifies withdrawal as a reduction in planarian movement. Planarians exposed to methamphetamine (10 mu M) for 60 min, and then placed (tested) into drug-free water for 5 min, displayed less movement (i.e., withdrawal) than either methamphetamine-naive planarians tested in water or methamphetamine-exposed planarians tested in methamphetamine. A concentration-related inhibition of withdrawal was observed when methamphetamine-exposed planarians were placed into a solution containing either methamphetamine and 5-HT (0.1-100 mu M) or methamphetamine and the 5-HT1A receptor agonist 8-hydroxy-N,N-dipropyl-2-aminotetralin (8-OH-DPAT) (10, 20 mu M). Planarians with prior methamphetamine exposure displayed enhanced withdrawal when tested in a solution of the 5-HT1A receptor antagonist N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridyl)cyclohexanecarboxamide (WAY 100635) (1 mu M). Methamphetamine-induced withdrawal was not affected by the 5-HT2B/2C receptor agonist meta-chlorophenylpiperazine (m-CPZ) (0.1-20 mu M). These results provide pharmacological evidence that serotonin-enhancing drugs inhibit expression of methamphetamine physical dependence in an invertebrate model of withdrawal, possibly through a 5-HT1A-like receptor-dependent mechanism. (C) 2010 Elsevier Ireland Ltd. All rights reserved.
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