neuronal nicotinic receptors as new targets for amphetamine-induced oxidative damage and neurotoxicity神经元烟碱受体作为amphetamine-induced氧化损伤和神经毒性的新目标.pdfVIP

Pharmaceuticals 2011, 4, 822-847; doi:10.3390/ph4060822 OPEN ACCESS Pharmaceuticals ISSN 1424-8247 /journal/pharmaceuticals Review Neuronal Nicotinic Receptors as New Targets for Amphetamine-Induced Oxidative Damage and Neurotoxicity David Pubill *, Sara Garcia-Ratés, Jordi Camarasa and Elena Escubedo Unitat de Farmacologia i Farmacognòsia, Facultat de Farmàcia, Universitat de Barcelona, 08028 Barcelona, Spain; E-Mails: sgarcira@ (S.G.-R.); jcamarasa@ (J.C.); eescubedo@ (E.E.) * Author to whom correspondence should be addressed; E-Mails: d.pubill@; Tel.: +34-93-402-4531; Fax: +34-93-403-5982. Received: 7 April 2011; in revised form: 3 June 2011 / Accepted: 7 June 2011 / Published: 15 June 2011 Abstract: Amphetamine derivatives such as methamphetamine (METH) and 3,4-methylenedioxymethamphetamine (MDMA, “ecstasy”) are widely abused drugs in a recreational context. This has led to concern because of the evidence that they are neurotoxic in animal models and cognitive impairments have been described in heavy abusers. The main targets of these drugs are plasmalemmal and vesicular monoamine transporters, leading to reverse transport and increased monoamine efflux to the synapse. As far as neurotoxicity is concerned, increased reactive oxygen species (ROS) production seems to be one of the main causes. Recent research has demonstrated that blockade of α7 nicotinic acetylcholine receptors (nAChR) inhibits METH- and MDMA-induced