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The atypical dopamine transport inhibitor, JHW 007, prevents amphetamine-induced sensitization and synaptic reorganization within the nucleus accumbens

Citation

Velazquez-Sanchez, C and Garcia-Verdugo, JM and Murga, J and Canales, JJ, The atypical dopamine transport inhibitor, JHW 007, prevents amphetamine-induced sensitization and synaptic reorganization within the nucleus accumbens, Progress in neuro-psychopharmacology & biological psychiatry, 44 pp. 73-80. ISSN 0278-5846 (2013) [Refereed Article]

DOI: doi:10.1016/j.pnpbp.2013.01.016

Abstract

Benztropine (BZT) analogs, a family of agents with high affinity for the dopamine transporter have been postulated as potential treatments in stimulant abuse due to their ability to attenuate a wide range of effects evoked by psychomotor stimulants such as cocaine and amphetamine (AMPH). Repeating administration of drugs, including stimulants, can result in behavioral sensitization, a progressive increase in their psychomotor activating effects. We examined in mice the sensitizing effects and the neuroplasticity changes elicited by chronic AMPH exposure, and the modulation of these effects by the BZT derivative and atypical dopamine uptake inhibitor, JHW007, a candidate medication for stimulant abuse. The results indicated that JHW007 did not produce sensitized locomotor activity when given alone but prevented the sensitized motor behavior induced by chronic AMPH administration. Morphological analysis of medium spiny neurons of the nucleus accumbens revealed that JHW 007 prevented the neuroadaptations induced by chronic AMPH exposure, including increments in dendritic arborization, lengthening of dendritic processes and increases in spine density. Furthermore, data revealed that AMPH produced an increase in the density of asymmetric, possibly glutamatergic synapses in the nucleus accumbens, an effect that was also blocked by JHW007 pretreatment. The present observations demonstrate that JHW007 is able to prevent not only AMPH-induced behavioral sensitization but also the long-term structural changes induced by chronic AMPH in the nucleus accumbens. Such findings support the development and evaluation of BZT derivatives as possible leads for treatment in stimulant addiction.

Item Details

Item Type:Refereed Article
Research Division:Psychology and Cognitive Sciences
Research Group:Psychology
Research Field:Biological Psychology (Neuropsychology, Psychopharmacology, Physiological Psychology)
Objective Division:Expanding Knowledge
Objective Group:Expanding Knowledge
Objective Field:Expanding Knowledge in Psychology and Cognitive Sciences
UTAS Author:Canales, JJ (Professor Juan Canales)
ID Code:121278
Year Published:2013
Web of Science® Times Cited:10
Deposited By:Psychology
Deposited On:2017-09-20
Last Modified:2017-09-20
Downloads:0

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