Benzodiazepines alter acquisition and retention of an inhibitory avoidance response in mice

Jensen, Robert A.; Martinez, Joe L.; Vasquez, Beatriz J.; McGaugh, James L.

doi:10.1007/bf00427358

Cited by 81 publications

(36 citation statements)

References 5 publications

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“…Results from the context test show that immediate post-training intrahippocampal infusion of midazolam attenuates freezing. These results are in agreement with data that demonstrate GABA A receptors are important for memory consolidation (Jensen et al 1979;Fanselow and Helmstetter 1988;Dickinson-Anson and McGaugh 1993;Izquierdo et al 1997;Zarrindast et al 2002;Rossato et al 2004). Our results extend previous findings to show that hippocampal infusion of the benzodiazepine midazolam also disrupts contextual fear conditioning when given immediately after training.…”

Section: Discussionsupporting

confidence: 93%

“…Benzodiazepines enhance the inhibitory actions of GABA at the GABA A receptor by increasing the frequency of chloride channel openings (Study and Barker 1981). Jensen et al (1979) showed that intraperitoneal (IP) injection of the benzodiazepine flurazepam immediately after training in an inhibitory avoidance task impaired memory. Fanselow and Helmstetter (1988) demonstrated that the benzodiazepines diazepam, midazolam, and chlordiazepoxide administered IP pretraining and/or pre-testing attenuated freezing to a context associated with shock.…”

mentioning

confidence: 99%

“…Based on research indicating muscimol (Zarrindast et al 2002;Rossato et al 2004) and benzodiazepines (Jensen et al 1979) impair memory at time points after training, the present experiments sought to test the importance of hippocampal GABA A receptors during early and late phases of consolidation. Animals received intrahippocampal infusion of midazolam or DMSO immediately or 3 h after training with pairings of white noise and shock.…”

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confidence: 99%

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Effects of post-training hippocampal injections of midazolam on fear conditioning

Gafford¹,

Parsons²,

Helmstetter³

2005

Learn. Mem.

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Benzodiazepines have been useful tools for investigating mechanisms underlying learning and memory. The present set of experiments investigates the role of hippocampal GABA A /benzodiazepine receptors in memory consolidation using Pavlovian fear conditioning. Rats were prepared with cannulae aimed at the dorsal hippocampus and trained with a series of white noise-shock pairings. In the first experiment, animals received intrahippocampal infusion of midazolam or vehicle immediately or 3 h after training. Then, 24 h later, freezing to the training context and the white noise were measured independently. Results show infusion of midazolam immediately, but not 3 h, after training selectively attenuates contextual fear conditioning. In the second experiment, animals received intrahippocampal infusions of an antisense oligodeoxynucleotide (ODN) targeting the ␣5 subunit of the GABA A receptor or a missense control for several days prior to training and testing. Immediately after training, animals received an infusion of either midazolam or vehicle. Western blots conducted after testing showed a significant decrease in ␣5-containing GABA A receptor protein. This reduction did not alter the effectiveness of midazolam immediately after training at impairing context fear memory. Therefore, ␣5-containing GABA A receptors may not contribute to the effects of midazolam on context fear conditioning when given immediately post-training.Pavlovian fear conditioning produces fear through learning that an aversive event is predicted by some neutral stimulus (for review, see LeDoux 2000;Maren 2001;Schafe et al. 2001). Rats quickly learn to associate a conditional stimulus (CS) with a noxious unconditional stimulus (US) and produce conditional responses (CRs) that can be reliably measured. In particular, freezing is a CR defined as the absence of all body movement except that related to respiration (Blanchard and Blanchard 1969;Fanselow 1980). Fear conditioning creates a long-lasting memory of the contextual and discrete cues present at the time of training.Post-training manipulations of the hippocampus have been shown to impair contextual fear conditioning (Kim and Fanselow 1992;Maren et al. 1997;Frankland et al. 1998;Anagnostaras et al. 1999;Barrientos et al. 2002;Dash et al. 2002;Wallenstein et al. 2002;Ji et al. 2003). One current area of research regarding the hippocampus is the analysis of the time course of mechanisms that underlie consolidation. Consolidation refers to the period after acquisition when a new memory transforms from an easily disrupted short-term state to a stable long-term memory (McGaugh 2000). Recent research using inhibitors of protein synthesis and gene expression suggests that memory for inhibitory avoidance has two phases of consolidation, one that occurs around the time of training and another occurring 3 to 6 h after training (Quevedo et al. 1999;Igaz et al. 2002). Similarly, the consolidation of contextual fear memory is also time dependent and may have multiple periods of susceptibility to protein sy...

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Section: Discussionsupporting

confidence: 93%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Effects of post-training hippocampal injections of midazolam on fear conditioning

Gafford¹,

Parsons²,

Helmstetter³

2005

Learn. Mem.

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“…Our previous results on rats in a Y-maze showed a correlation to the present data concerning the mode of the disruptive effects of scopolamine and diazepam (7). Although the "amnesic" effects of benzodiazepines has been reported (11,24), its apparent disruptive effects on memory might be caused by some other factors such as attentional or motivational deficits.…”

Section: Discussionmentioning

confidence: 99%

“…Nicotine was selected because it may facilitate (8) or impair (9) the memory process. Scopolamine and diaz epam were selected because they may have amnesic effects (10,11 …”

mentioning

confidence: 99%

Effects of Psychoactive Drugs on Short-Term Memory in Rats and Rhesus Monkeys

Hironaka

Miyata

Ando

1992

Japanese Journal of Pharmacology

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ABSTRACT-To examine the effects of drugs on short-term memory in animals, the delayed discri mination experiment in rats and the delayed matching to sample experiment in rhesus monkeys were conducted. Nicotine at 0.125 mg/kg, s.c. in rats and at 0.5 mg/kg, s.c. in monkeys increased the per centages of correct choices. Scopolamine at 0.06-0.12 mg/kg, s.c. in rats and at 0.015 mg/kg, s.c. in monkeys decreased the percentages of correct choices. However, supposedly memory-specific, delay time-dependent disruptive effects by scopolamine were found only in monkeys. Diazepam at 0.5-2 mg/kg, s.c. did not change the correct choices in rats. However, diazepam at 1-4 mg/kg, i.g. de creased the correct choices in monkeys regardless of the delay time. Chlorpromazine at 0.25-1.5 mg/kg, s.c. showed inconsistent effects in rats. In monkeys, chlorpromazine at 0.25-0.5 mg/kg, s.c. had no effect. These results suggested that using both rats and monkeys would be useful for evaluating the effects of drugs on memory.

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Experimental dysnesia induced by 1, 4- but not by 1,5-benzodiazepines

Giurgea¹,

Greindl²,

Preat³

1982

Drug Dev. Res.

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Giurgea, C.E., M.G. Greindl, and S. Preat: Experimental dysnesia induced by 1,4-but not by 1,5benzodiazepines. Drug Dev. Res. S1:023-031, 1982.1,4-benzodiazepines (BDZs) are known to induce mild but consistent dysmnesia in several animal models and in humans, whereas the 1 5 B D Z clobazam is claimed to be devoid of this adverse effect. Systematic animal studies comparing 13-to 1,4-BDZs in this field are lacking. The "threshold" conditioned escape response (t-CER) in the Wistar rat, a recently described learning and memory model, is known to discriminate between 1 3 -and 1,4-BDZs. In this model it has been shown that: all 1 ,4-BDZs studied induce a definite dysmnesia (retention and/or acquisition impairments and, with the exception of diazepam, retrieval impairment); 1 ,4-BDZ dysmnesia is not due to an eventual state-dependency learning; many other psychotropic drugs, in usual doses, do not impair t-CER performances; 1 3 -BDZs (clobazam and triflubazam) do not interfere, even in high doses, with t-CER performance.

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Benzodiazepines alter acquisition and retention of an inhibitory avoidance response in mice

Cited by 81 publications

References 5 publications

Effects of post-training hippocampal injections of midazolam on fear conditioning

Effects of post-training hippocampal injections of midazolam on fear conditioning

Effects of Psychoactive Drugs on Short-Term Memory in Rats and Rhesus Monkeys

Experimental dysnesia induced by 1, 4- but not by 1,5-benzodiazepines

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