Comparison of the long-term consequences of withdrawal from repeated amphetamine exposure in adolescence and adulthood on information processing and locomotor sensitization in mice

Juliet Richetto, Joram Feldon, Marco A. Riva, Urs Meyer*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

Repeated administration of the indirect dopamine receptor agonist amphetamine (AMPH) produces robust locomotor sensitization and additional behavioral abnormalities. Accumulating evidence suggests that the developmental timing of drug exposure can critically influence this effect. The present study compared the consequences of withdrawal from repeated AMPH exposure in adolescence and adulthood on information processing and locomotor sensitization in C57BL/6 mice. Animals were injected daily with AMPH (1 or 2.5. mg/kg) or vehicle on 7 consecutive days starting either from postnatal day 35 to 42, or from postnatal day 70 to 77, following which they were given a 4 week withdrawal period before behavioral and pharmacological testing commenced. We found that withdrawal from the higher dose of AMPH (2.5. mg/kg/day) given either in adolescence or adulthood similarly disrupted selective associative learning as measured by the latent inhibition paradigm. None of the AMPH withdrawal groups displayed alterations in sensorimotor gating in the form of prepulse inhibition. Withdrawal from adult AMPH exposure at both doses induced marked locomotor sensitization, whereas adolescent pre-treatment with the higher (2.5. mg/kg/day) but not lower (1. mg/kg/day) dose of AMPH potentiated the locomotor-enhancing effects of acute AMPH re-challenge. Our study suggests that withdrawal from repeated AMPH exposure in adolescence and adulthood has similar consequences on selective associative learning, but the two manipulations differ with respect to their efficacy to induce long-term locomotor sensitization to the drug. The latter finding supports the hypothesis that the precise developmental timing determines, at least in part, the impact on long-term dopamine-associated sensitization processes.

Original languageEnglish
Pages (from-to)160-170
Number of pages11
JournalEuropean Neuropsychopharmacology
Volume23
Issue number2
DOIs
StatePublished - Feb 2013
Externally publishedYes

Funding

FundersFunder number
Italian Ministry of Health
Italian Ministry of University and Research2007STRNHK
Swiss Federal Institute of Technology
Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung3100AO-100309, 3100AO-116719
Eidgenössische Technische Hochschule Zürich11 07/03

    Keywords

    • Amphetamine
    • Dopamine
    • Latent inhibition
    • Prepulse inhibition
    • Schizophrenia
    • Sensitization

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