Environmental modulation of ethanol-induced locomotor activity: Correlation with neuronal activity in distinct brain regions of adolescent and adult Swiss mice.
Drug abuse is a concerning health problem in adults and has been recognized as a major problem in adolescents. Induction of immediate-early genes (IEG), such as c-Fos or Egr-1, is used to identify brain areas that become activated in response to various stimuli, including addictive drugs. It is known that the environment can alter the response to drugs of abuse. Accordingly, environmental cues may trigger drug-seeking behavior when the drug is repeatedly administered in a given environment. The goal of this study was first to examine for age differences in context-dependent sensitization and then evaluate IEG expression in different brain regions. For this, groups of mice received i.p. ethanol (2.0 g/kg) or saline in the test apparatus, while other groups received the solutions in the home cage, for 15 days. One week after this treatment phase, mice were challenged with ethanol injection. Acutely, ethanol increased both locomotor activity and IEG expression in different brain regions, indistinctly, in adolescent and adult mice. However, adults exhibited a typical context-dependent behavioral sensitization following repeated ethanol treatment, while adolescent mice presented gradually smaller locomotion across treatment, when ethanol was administered in a paired regimen with environment. Conversely, ethanol-treated adolescents expressed context-independent behavioral sensitization. Overall, repeated ethanol administration desensitized IEG expression in both adolescent and adult mice, but this effect was greatest in the nucleus accumbens and prefrontal cortex of adolescents treated in the context-dependent paradigm. These results suggest developmental differences in the sensitivity to the conditioned and unconditioned locomotor effects of ethanol.
Faria
Rulian Ricardo
RR
Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Av. Prof. Lineu Prestes, 1524, São Paulo, SP, 05508-900, Brazil.
Lima Rueda
André Veloso
AV
Sayuri
Cristina
C
Soares
Sabrina Lucio
SL
Malta
Marília Brinati
MB
Carrara-Nascimento
Priscila Fernandes
PF
da Silva Alves
Adilson
A
Marcourakis
Tânia
T
Yonamine
Maurício
M
Scavone
Cristoforo
C
Giorgetti Britto
Luiz Roberto
LR
Camarini
Rosana
R
D000375:Aging; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000187:drug effects* / Q000502:physiology; D002492:Central Nervous System Depressants / Q000097:blood / Q000494:pharmacology*; D003463:Cues; D051766:Early Growth Response Protein 1 / Q000378:metabolism; D004777:Environment; D000431:Ethanol / Q000097:blood / Q000494:pharmacology*; D017781:Genes, Immediate-Early / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology; D008124:Locomotion / Q000187:drug effects / Q000502:physiology; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects* / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D009714:Nucleus Accumbens / Q000187:drug effects / Q000502:physiology; D017397:Prefrontal Cortex / Q000187:drug effects / Q000502:physiology; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism
D002492:Central Nervous System Depressants; D051766:Early Growth Response Protein 1; C486109:Egr1 protein, mouse; D016760:Proto-Oncogene Proteins c-fos; D000431:Ethanol