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Replacement treatment during extinction training with the atypical dopamine uptake inhibitor, JHW-007, reduces relapse to methamphetamine seeking.
Neurosci Lett. 2018 04 03; 671:88-92.NL

Abstract

There are currently no approved medications to effectively counteract the effects of methamphetamine (METH), reduce its abuse and prolong abstinence from it. Data accumulated in recent years have shown that a range of N-substituted benztropine (BZT) analogues possesses psychopharmacological features consistent with those of a potential replacement or "substitute" treatment for stimulant addiction. On the other hand, the evidence that antidepressant therapy may effectively prevent relapse to stimulant seeking is controversial. Here, we compared in rats the ability of the BZT analogue and high affinity dopamine (DA) reuptake inhibitor, JHW-007, and the antidepressant, trazodone, administered during extinction sessions after chronic METH self-administration, to alter METH-primed reinstatement of drug seeking. The data showed that trazodone produced paradoxical effects on lever pressing during extinction of METH self-administration, decreasing active, but increasing inactive, lever pressing. JHW-007 did not have any observable effects on extinction training. Importantly, JHW-007 significantly attenuated METH-primed reinstatement, whereas trazodone enhanced it. These findings lend support to the candidacy of selective DA uptake blockers, such as JHW-007, as potential treatments for METH addiction, but not to the use of antidepressant medication as a single therapeutic approach for relapse prevention.

Authors+Show Affiliations

Division of Psychology, School of Medicine, University of Tasmania, Private Bag 30, Hobart, TAS, 7001, Australia.Division of Psychology, School of Medicine, University of Tasmania, Private Bag 30, Hobart, TAS, 7001, Australia. Electronic address: juan.canales@utas.edu.au.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

29452175

Citation

Dassanayake, Ashlea F., and Juan J. Canales. "Replacement Treatment During Extinction Training With the Atypical Dopamine Uptake Inhibitor, JHW-007, Reduces Relapse to Methamphetamine Seeking." Neuroscience Letters, vol. 671, 2018, pp. 88-92.
Dassanayake AF, Canales JJ. Replacement treatment during extinction training with the atypical dopamine uptake inhibitor, JHW-007, reduces relapse to methamphetamine seeking. Neurosci Lett. 2018;671:88-92.
Dassanayake, A. F., & Canales, J. J. (2018). Replacement treatment during extinction training with the atypical dopamine uptake inhibitor, JHW-007, reduces relapse to methamphetamine seeking. Neuroscience Letters, 671, 88-92. https://doi.org/10.1016/j.neulet.2018.02.025
Dassanayake AF, Canales JJ. Replacement Treatment During Extinction Training With the Atypical Dopamine Uptake Inhibitor, JHW-007, Reduces Relapse to Methamphetamine Seeking. Neurosci Lett. 2018 04 3;671:88-92. PubMed PMID: 29452175.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Replacement treatment during extinction training with the atypical dopamine uptake inhibitor, JHW-007, reduces relapse to methamphetamine seeking. AU - Dassanayake,Ashlea F, AU - Canales,Juan J, Y1 - 2018/02/13/ PY - 2017/10/20/received PY - 2018/01/26/revised PY - 2018/02/12/accepted PY - 2018/2/17/pubmed PY - 2019/2/20/medline PY - 2018/2/17/entrez KW - Extinction KW - JHW-007 KW - Methamphetamine KW - Reinstatement KW - Trazodone SP - 88 EP - 92 JF - Neuroscience letters JO - Neurosci. Lett. VL - 671 N2 - There are currently no approved medications to effectively counteract the effects of methamphetamine (METH), reduce its abuse and prolong abstinence from it. Data accumulated in recent years have shown that a range of N-substituted benztropine (BZT) analogues possesses psychopharmacological features consistent with those of a potential replacement or "substitute" treatment for stimulant addiction. On the other hand, the evidence that antidepressant therapy may effectively prevent relapse to stimulant seeking is controversial. Here, we compared in rats the ability of the BZT analogue and high affinity dopamine (DA) reuptake inhibitor, JHW-007, and the antidepressant, trazodone, administered during extinction sessions after chronic METH self-administration, to alter METH-primed reinstatement of drug seeking. The data showed that trazodone produced paradoxical effects on lever pressing during extinction of METH self-administration, decreasing active, but increasing inactive, lever pressing. JHW-007 did not have any observable effects on extinction training. Importantly, JHW-007 significantly attenuated METH-primed reinstatement, whereas trazodone enhanced it. These findings lend support to the candidacy of selective DA uptake blockers, such as JHW-007, as potential treatments for METH addiction, but not to the use of antidepressant medication as a single therapeutic approach for relapse prevention. SN - 1872-7972 UR - https://www.unboundmedicine.com/medline/citation/29452175/Replacement_treatment_during_extinction_training_with_the_atypical_dopamine_uptake_inhibitor,_JHW-007,_reduces_relapse_to_methamphetamine_seeking L2 - https://linkinghub.elsevier.com/retrieve/pii/S0304-3940(18)30101-0 DB - PRIME DP - Unbound Medicine ER -