title: Early life stress decreases hippocampal BDNF content and exacerbates recognition memory deficits induced by repeated D-amphetamine exposure.
abstract: Adverse experiences early in life may have profound influences on brain development, for example, determining alterations in response to psychostimulant drugs, an increased risk of developing a substance abuse disorder, and individual differences in the vulnerability to neuropsychiatric disorders later in life. Here, we investigated the effects of exposure to an early adverse life event, maternal deprivation, combined with repeated d-amphetamine (AMPH) administration in adulthood, on recognition memory and brain-derived neurotrophic factor (BDNF) levels in rats' brain and serum. Rats were exposed to one of the following maternal rearing conditions from postnatal days 1 to 14: non-deprived (ND) or deprived (D). In adulthood, both groups received injections of saline (SAL) or AMPH (2.0mg/kg, i.p.) for 7 days. In Experiment I (performed 24h after the last AMPH injection), AMPH induced long-term memory (LTM) impairments in ND and D groups. The D+AMPH group also presented short-term memory (STM) impairments, indicating that the effects of AMPH on memory were more pronounced when the animals where maternally deprived. The group exposed to D+SAL (SAL) showed only LTM impairments. In Experiment II (performed 8 days after the last injection), AMPH detrimental effects on memory persisted in ND and D groups. BDNF levels were decreased in the hippocampus of D+SAL rats. In conclusion, AMPH produces severe and persistent recognition memory impairments that were more pronounced when the animals were maternally deprived, suggesting that an early adverse life event may increase the vulnerability of cognitive function to exposure to a psychostimulant later in life.
authors.affiliation: Neurobiology and Developmental Biology Laboratory, Faculty of Biosciences, Pontifical Catholic University, 90619-900 Porto Alegre, RS, Brazil.
authors.forename: Maria Noêmia Martins
authors.initials: MN
authors.lastname: de Lima
authors.forename: Juliana
authors.initials: J
authors.lastname: Presti-Torres
authors.forename: Gustavo
authors.initials: G
authors.lastname: Vedana
authors.forename: Luisa Azambuja
authors.initials: LA
authors.lastname: Alcalde
authors.forename: Laura
authors.initials: L
authors.lastname: Stertz
authors.forename: Gabriel Rodrigo
authors.initials: GR
authors.lastname: Fries
authors.forename: Rafael
authors.initials: R
authors.lastname: Roesler
authors.forename: Monica Levy
authors.initials: ML
authors.lastname: Andersen
authors.forename: João
authors.initials: J
authors.lastname: Quevedo
authors.forename: Flávio
authors.initials: F
authors.lastname: Kapczinski
authors.forename: Nadja
authors.initials: N
authors.lastname: Schröder
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D000697:Central Nervous System Stimulants / Q000009:adverse effects*; D003913:Dextroamphetamine / Q000009:adverse effects*; D004195:Disease Models, Animal; D005106:Exploratory Behavior / Q000187:drug effects; D005260:Female; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D008426:Maternal Deprivation; D011247:Pregnancy; D051381:Rats; D013315:Stress, Psychological / Q000150:complications* / Q000473:pathology*; D013997:Time Factors
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D000697:Central Nervous System Stimulants; D003913:Dextroamphetamine