Trace amine associated receptors : a new target for medications in drug addiction

dc.contributor.authorCotter, Rachel
dc.date.accessioned2015-08-20T02:51:28Z
dc.date.available2017-05-04T20:12:57Z
dc.date.issued2012en
dc.description.abstractThe abuse of stimulant drugs, such as methamphetamine (METH), has become a major source of public concern in New Zealand. Specific medications for treating METH addiction are not available at present. The newly discovered trace amine- associated receptor 1 (TAAR1) constitutes a novel receptor target for medication development in neuropsychiatry. TAAR1 regulates monoamine systems in the brain, especially dopamine, and is activated directly by psychomotor stimulants, including METH. This study examined the effects of the newly developed TAAR1 partial agonist, RO5203648, in rat models of METH abuse. In experiment 1 rats were administered different doses of RO5203648 (0, 1.67, 5mg/kg i.p.) followed by METH (0, 0.75, 2mg/kg i.p.). Locomotor activity was monitored via automated video tracking system in an open field. The results revealed that RO5203648 dose- dependently reduced acute METH-induced stimulation and prevented long-term sensitization following chronic exposure. Paradoxically, in experiment 2, RO5203648 and METH treatment increased c-Fos protein expression in the nucleus accumbens and dorsal striatum. In experiment 3 rats were trained to consistently self-administer METH (0.5mg/kg/infusion) and were then pre-treated with RO5203648 (0, 3, 10mg/kg i.p.). The data showed that RO5203648 drastically reduced METH intake. Next, RO5203648 was substituted (0.25, 0.5, 1.0 mg/kg/infusion) for METH in the same paradigm. Remarkably, RO5203648 exhibited no reinforcing efficacy compared with METH. Taken together, these observations showed that RO5203648 is able to attenuate METH-related behaviours, including locomotor stimulation, sensitization and self-administration, and highlight the great potential of TAAR1-based medications for the treatment of METH addiction.en
dc.identifier.urihttp://hdl.handle.net/10092/10803
dc.identifier.urihttp://dx.doi.org/10.26021/5624
dc.language.isoen
dc.publisherUniversity of Canterbury. Psychologyen
dc.relation.isreferencedbyNZCUen
dc.rightsCopyright Rachel Cotteren
dc.rights.urihttps://canterbury.libguides.com/rights/thesesen
dc.subjectDrug Addictionen
dc.subjectMethamphetamineen
dc.subjectMedicationen
dc.subjectTrace Amine Associated Receptor 1en
dc.subjectanimal modelen
dc.titleTrace amine associated receptors : a new target for medications in drug addictionen
dc.typeTheses / Dissertations
thesis.degree.disciplinePsychology
thesis.degree.grantorUniversity of Canterburyen
thesis.degree.levelMastersen
thesis.degree.nameMaster of Scienceen
uc.bibnumber2122574
uc.collegeFaculty of Scienceen
uc.embargo12en
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