Nanotherapeutic Approach for Opiate Addiction Usin

Authors: T A Ignatowski R Aalinkeel J L Reynolds B B Nair D E Sykes C P K Gleason W C Law M J Mammen P N Prasad S A Schwartz Supriya D Mahajan

Publish Date: 2015/01/22

Volume: 10, Issue: 1, Pages: 136-152

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Abstract

Opiates act on the dopaminergic system of the brain and perturb 32 kDa dopamine and adenosine 3′ 5′monophosphateregulated phosphoprotein DARPP32 function The DARPP32 mediated inhibition of protein phosphatase1 PP1 and modulation of transcriptional factor CREB is critical to the changes in neuronal plasticity that result in behavioral responses during drug abuse To investigate the role of DARPP32 mediated signaling on withdrawal behavior in a rat model of opiate addiction we used intracerebral administration of gold nanorods GNR complexed to DARPP32 siRNA to silence DARPP32 gene expression and measure its effects on the opiate withdrawal syndrome We hypothesized that DARPP32 siRNA will suppress the neurochemical changes underlying the withdrawal syndrome and therefore prevent conditioned place aversion by suppressing or removing the constellation of negative effects associated with withdrawal during the conditioning procedure Our results showed that opiate addicted animals treated with GNRDARPP32 siRNA nanoplex showed lack of condition place aversive behavior consequent to the downregulation of secondary effectors such as PP1 and CREB which modify transcriptional gene regulation and consequently neuronal plasticity Thus nanotechnology based delivery systems could allow sustained knockdown of DARPP32 gene expression which could be developed into a therapeutic intervention for treating drug addiction by altering reward and motivational systems and interfere with conditioned responses

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