Effects of zolpidem on sedation, anxiety, and memory in the plus-maze discriminative avoidance task
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Zolpidem (Zolp), a hypnotic drug prescribed to treat insomnia, may have negative effects on memory, but reports are inconsistent.
We examined the effects of acute doses of Zolp (2, 5, or 10 mg/kg, i.p.) on memory formation (learning, consolidation, and retrieval) using the plus-maze discriminative avoidance task.
Mice were acutely treated with Zolp 30 min before training or testing. In addition, the effects of Zolp and midazolam (Mid; a classic benzodiazepine) on consolidation at different time points were examined. The possible role of state dependency was investigated using combined pre-training and pre-test treatments.
Zolp produced a dose-dependent sedative effect, without modifying anxiety-like behavior. The pre-training administration of 5 or 10 mg/kg resulted in retention deficits. When administered immediately after training or before testing, memory was preserved. Zolp post-training administration (2 or 3 h) impaired subsequent memory. There was no participation of state dependency phenomenon in the amnestic effects of Zolp. Similar to Zolp, Mid impaired memory consolidation when administered 1 h after training.
Amnestic effects occurred when Zolp was administered either before or 2–3 h after training. These memory deficits are not related to state dependency. Moreover, Zolp did not impair memory retrieval. Notably, the memory-impairing effects of Zolp are similar to those of Mid, with the exception of the time point at which the drug can modify consolidation. Finally, the memory effects were unrelated to sedation or anxiolysis.
KeywordsZolpidem Memory Consolidation State dependency Plus-maze discriminative avoidance task PM-DAT
This research was supported by fellowships from Fundação de Amparo a Pesquisa do Estado de São Paulo (FAPESP: CEPID #1998/14303-3; KAZ #2008/08823-8; CLP #2009/00465-8), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Fundação Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), and Associação Fundo de Incentivo à Pesquisa (AFIP). This manuscript was checked for English language by the American Journal Experts (AJE) and by Dr. Eileen Sawyer, but we are entirely responsible for the scientific content of the paper. The authors would like to thank Ms. Teotila R. R. Amaral, Ms. Claudenice M. Santos, Mr. Cleomar S. Ferreira, and Mr. Antonio Rodrigues dos Santos Ferreira for capable technical assistance. D.P., S.T, and R.F.F. are recipients of the CNPq fellowship. Animals were maintained in accordance with the Brazilian Law for Procedures for Animal Scientific Use (#11794/2008) and all the experimental procedures were approved by the Institutional Animal Care and Use Committee (#1126/08).
Conflict of interest
All authors declare no conflict of interests and had no disclosures.
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