Journal
PSYCHOPHARMACOLOGY
Volume 193, Issue 1, Pages 107-120Publisher
SPRINGER
DOI: 10.1007/s00213-007-0751-x
Keywords
opioid; methadone; tolerance; dependence; opioid withdrawal; learning and memory; apoptosis; Bcl-2; Fas
Categories
Ask authors/readers for more resources
Objectives This study analyzes the effects of prolonged administration of methadone and withdrawal on sensorimotor and cognitive performance in mice and explores the associated changes in brain expression of proteins regulating the extrinsic (FasL, Fas, and caspase-8) and the mitochondrial (Bcl-2, Bcl-x(L), Bad, and Bax) apoptotic pathways. Results Our findings indicate that, although acute methadone administration impairs some sensorimotor abilities, tolerance to most of the deleterious effects develops after chronic administration. Cognitive abilities in the Morris water maze were impaired by chronic methadone and, to a greater extent, by exposure to precipitated withdrawal every week in the course of methadone treatment. Both the chronic methadone and repeated withdrawal groups showed up-regulation of several pro-apoptotic proteins (FasL, the active fragment of caspase-8, and Bad) in the cortex and hippocampus, indicating activation of both the death-receptor and mitochondrial apoptotic pathways. In contrast, reduced expression of the apoptosis regulatory proteins FasL and Bad was found after a single administration of methadone. Conclusions Our data suggest that neural apoptotic damage could contribute to impairment of the cognitive abilities of mice observed after chronic methadone administration and withdrawal.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available