Effects of zolpidem on sedation, anxiety, and memory in the plus-maze discriminative avoidance task.
BACKGROUND
Zolpidem (Zolp), a hypnotic drug prescribed to treat insomnia, may have negative effects on memory, but reports are inconsistent.


OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Departamento de Psicobiologia, Universidade Federal de São Paulo, R. Napoleão de Barros, 925, 04024002 São Paulo, SP, Brazil.
Karina A
KA
Zanin
Camilla L
CL
Patti
Leandro
L
Sanday
Luciano
L
Fernandes-Santos
Larissa C
LC
Oliveira
Dalva
D
Poyares
Sergio
S
Tufik
Roberto
R
Frussa-Filho
D000818:Animals; D001007:Anxiety / Q000188:drug therapy; D001362:Avoidance Learning / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects; D004193:Discrimination Learning / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006993:Hypnotics and Sedatives / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D018782:Maze Learning / Q000187:drug effects*; D008568:Memory / Q000187:drug effects*; D051379:Mice; D011725:Pyridines / Q000008:administration & dosage / Q000494:pharmacology*; D013997:Time Factors; D000077334:Zolpidem
D006993:Hypnotics and Sedatives; D011725:Pyridines; D000077334:Zolpidem