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Methadone is substantially less effective than morphine in modifying locomotor and brain Fos responses to subsequent methadone challenge in rats.

Abstract：

:Heroin addicts can benefit from methadone substitution therapy. However, little is known about the significance of pre-exposure to opioids for psychoactive effects of methadone. We modeled some behavioral and neurobiological aspects of the opioid abuse-related phenomena in Sprague-Dawley rats, using morphine (10 mg/kg/day) or methadone (1 or 2 mg/kg/day) treatment (14 doses over a 16-day period) followed by 2-week withdrawal and methadone challenge; control rats were given 0.9% NaCl treatment and methadone challenge by the same schedule. Locomotor response to the challenge showed substantial enhancement only after the morphine treatment. Fos immunohistochemistry in selected brain regions including cortex, nucleus accumbens, striatum and some parts of the hippocampus, thalamus and amygdala also revealed marked differences between the effects of the tested treatments. Sensitization of Fos response was found in a few regions of the morphine-treated rats. The rats given the higher methadone dose treatment showed a fairly weak tendency for sensitization that reached significance only in somatosensory cortex layer IV. The rats given the lower methadone dose treatment showed a weak while widespread tendency for an opposite change, which reached significance in cingulate cortex layer II/III and resulted in significant differences in Fos response between these rats and the morphine-treated rats in most regions studied. These results indicate that lasting neuroplastic changes associated with the sensitization caused by (sub)chronic exposure to opioids are relatively mild for methadone as compared to those caused by morphine, and suggest that psychoactive effects of methadone can be notably enhanced by past opiate use.

journal_name

Prog Neuropsychopharmacol Biol Psychiatry

journal_title

Progress in neuro-psychopharmacology & biological psychiatry

authors

Taracha E,Chrapusta SJ,Lehner M,Skórzewska A,Płaźnik A

doi

10.1016/j.pnpbp.2009.05.015

subject

Has Abstract

pub_date

2009-08-31 00:00:00

pages

1032-9

issue

eissn

0278-5846

issn

1878-4216

pii

S0278-5846(09)00167-5

journal_volume

pub_type

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Methadone is substantially less effective than morphine in modifying locomotor and brain Fos responses to subsequent methadone challenge in rats.