title: Comparison of the long-term consequences of withdrawal from repeated amphetamine exposure in adolescence and adulthood on information processing and locomotor sensitization in mice.
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.
authors.affiliation: Center of Neuropharmacology, Department of Pharmacological Sciences, Università degli Studi di Milano, Via Balzaretti 9, 20133 Milan, Italy.
authors.forename: Juliet
authors.initials: J
authors.lastname: Richetto
authors.forename: Joram
authors.initials: J
authors.lastname: Feldon
authors.forename: Marco A
authors.initials: MA
authors.lastname: Riva
authors.forename: Urs
authors.initials: U
authors.lastname: Meyer
mesh_terms: D000367:Age Factors; D000375:Aging / Q000187:drug effects / Q000502:physiology*; D000661:Amphetamine / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001245:Association Learning / Q000187:drug effects / Q000502:physiology; D059333:Central Nervous System Sensitization / Q000187:drug effects / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D046353:Immobility Response, Tonic / Q000502:physiology; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology*; D009433:Neural Inhibition / Q000502:physiology*; D013216:Reflex, Startle / Q000187:drug effects / Q000502:physiology; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology* / Q000523:psychology*
chemical_list: D000661:Amphetamine