Dopamine and norepinephrine transporter inhibition for long-term fear memory enhancement.
Behav Brain Res
; 378: 112266, 2020 01 27.
Article
em En
| MEDLINE
| ID: mdl-31580915
ABSTRACT
Psychostimulants are highly effective cognitive-enhancing therapeutics yet have a significant potential for abuse and addiction. While psychostimulants likely exert their rewarding and addictive properties through dopamine transporter (DAT) inhibition, the mechanisms of their procognitive effects are less certain. By one prevalent view, psychostimulants exert their procognitive effects exclusively through norepinephrine transporter (NET) inhibition, however increasing evidence suggests that DAT also plays a critical role in their cognitive-enhancing properties, including long-term memory enhancement. The present experiments test the hypothesis that combined strong NET and weak DAT inhibition will mimic the fear memory-enhancing but not the addiction-related effects of psychostimulants in mice. We examined the effects of the high affinity NET inhibitors atomoxetine or nisoxetine and the low affinity DAT inhibitor bupropion, either alone or in combination, on short- and long-term memory of Pavlovian fear conditioning. We also examined the addiction-related effects of combined strong NET and weak DAT inhibition using conditioned place preference and a locomotor activity test. While atomoxetine or nisoxetine alone enhanced short-term fear memory, the addition of bupropion was required to significantly enhance long-term fear memory. Additionally, combined atomoxetine and bupropion did not produce substantial motor stimulation or place preference. These findings suggest that combining strong NET and weak DAT inhibition could lead to the development of a highly effective cognitive enhancer that lacks the potential for addiction.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Comportamento Animal
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Fluoxetina
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Bupropiona
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Inibidores da Captação de Neurotransmissores
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Nootrópicos
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Condicionamento Clássico
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Proteínas da Membrana Plasmática de Transporte de Dopamina
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Proteínas da Membrana Plasmática de Transporte de Norepinefrina
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Medo
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Memória de Longo Prazo
Limite:
Animals
Idioma:
En
Revista:
Behav Brain Res
Ano de publicação:
2020
Tipo de documento:
Article