Regional changes in ∆FosB expression in rat brain following MDMA self‐administration predict increased sensitivity to effects of locally infused MDMA

Ross Van de Wetering; Susan Schenk

doi:10.1111/adb.12814

Regional changes in ∆FosB expression in rat brain following MDMA self‐administration predict increased sensitivity to effects of locally infused MDMA

Ross Van de Wetering, Susan Schenk

Addiction Biology September 1, 2020 DOI: 10.1111/adb.12814 (opens in new tab)

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Study at a glance

AI-extracted from the abstract

Characteristics	Experimental study Peer reviewed
Population	Sexually mature male Sprague-Dawley rats
Intervention	MDMA
Dose	10.0 mg/kg (ip, once daily for 5 days) for pretreatment; 200 μg/side for microinjection
Duration	5-day pretreatment; self-administration duration not specified
Measures	immunohistochemical measurements of ΔFosB accumulation; locomotor activity
Topics	MDMA
Citations	9
Key findings	MDMA self-administration increased ΔFosB expression in specific brain regions, and MDMA pretreatment enhanced hyperactivity only when injected into those same regions, supporting common neuroplastic changes across drugs of abuse.

Abstract

AbstractRepeated exposure to drugs produces a plethora of persistent brain changes, some of which underlie the development of drug addiction. An important objective of addiction research is to identify the brain changes that might mediate the transition from drug use to drug misuse. The persistent accumulation of the transcription factor, ∆FosB, following repeated drug exposure provides a means of achieving this objective. Experiments were conducted on sexually mature male Sprague‐Dawley rats. The effects of extensive 3,4‐methylenedioxymethamphetamine (MDMA) self‐administration on immunohistochemical measurements of ∆FosB accumulation in 12 brain regions was compared with a matched, drug‐naive, control group. Other groups were pretreated with MDMA (0.0 or 10.0 mg/kg, ip, once daily for 5 days), and the locomotor‐activating effect of MDMA (200 μg/side) microinjected bilaterally into brain regions selected on the basis of the ∆FosB results was subsequently determined. MDMA self‐administration significantly increased ∆FosB expression in the nucleus accumbens core, ventromedial and dorsomedial caudate‐putamen, anterior cingulate, prelimbic, infralimbic, and orbitofrontal cortex, and both the central and basolateral amygdala, but not in the ventrolateral or dorsolateral caudate‐putamen. Increases in the nucleus accumbens shell were substantial but were not significant following statistical correction for multiple comparisons. MDMA pretreatment enhanced MDMA‐produced hyperactivity only when administered into the nucleus accumbens or the medial, but not the lateral, caudate‐putamen, mirroring the ∆FosB results. These data compare favorably to results following repeated exposure to other drugs of abuse and support the idea of common neuroplastic changes following repeated drug exposure.

Comparable studies

Other preclinical and animal studies on MDMA, most cited first.

Study	Year	Design
Neurotoxicity of the psychedelic amphetamine, methylenedioxymethamphetamine. Rats (implied by typical neurochemical study context)	1987	Experimental study
3,4-Methylenedioxymethamphetamine and 3,4-methylenedioxyamphetamine destroy serotonin terminals in rat brain: quantification of neurodegeneration by measurement of [3H]paroxetine-labeled serotonin uptake sites. Rat brain	1987	Animal experiment
Comparison of the monoamine transporters from human and mouse in their sensitivities to psychostimulant drugs Human and mouse dopamine, norepinephrine, and serotonin transporters expressed in cells	2006	In vitro laboratory study
Small Changes in Ambient Temperature Cause Large Changes in 3,4-Methylenedioxymethamphetamine (MDMA)-Induced Serotonin Neurotoxicity and Core Body Temperature in the Rat Rats	1998	Experimental study
Altered Serotonin Innervation Patterns in the Forebrain of Monkeys Treated with (±)3,4-Methylenedioxymethamphetamine Seven Years Previously: Factors Influencing Abnormal Recovery Squirrel monkeys treated with MDMA	1999	Observational cohort

Citations in the library

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