University of Tasmania
Browse

File(s) not publicly available

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

journal contribution
posted on 2023-05-19, 11:18 authored by Velazquez-Sanchez, C, Garcia-Verdugo, JM, Murga, J, Canales, JJ
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.

History

Publication title

Progress in neuro-psychopharmacology & biological psychiatry

Volume

44

Pagination

73-80

ISSN

0278-5846

Department/School

School of Psychological Sciences

Publisher

Pergamon-Elsevier Science Ltd

Place of publication

United Kingdom

Repository Status

  • Restricted

Socio-economic Objectives

Expanding knowledge in psychology

Usage metrics

    University Of Tasmania

    Exports

    RefWorks
    BibTeX
    Ref. manager
    Endnote
    DataCite
    NLM
    DC