Cycloheximide-induced amnesia for taste aversion memory in rats

doi:10.1016/0091-3057(76)90012-5

Pharmacology Biochemistry and Behavior

Volume 4, Issue 2, February 1976, Pages 181-184

https://doi.org/10.1016/0091-3057(76)90012-5 Get rights and content

Abstract

Male hooded rats were conditioned in one trial to avoid saccharin by pairing saccharin drinking with an intragastric injection of LiCl. A 24 hr water-saccharin preference test showed that conditioned rats exhibited a very low preference for saccharin whereas rats injected intraventricularly with cycloheximide (CXM, 400 μg) 5, 7, or 9 hr before training exhibited a greatly increased saccharin preference which differed significantly from NaCl injected controls. This 24 hr amnesia was found to be dependent upon the time of administration of CXM, since injection at 1, 3 or 17 hr before training did not confer amnesia. The nature of the task, a control measure and a control experiment indicate that the CXM-induced change in saccharin preference at 24 hr is not due to a CXM-induced aversion, nor a loss in drinking ability nor an inability to retrieve information whilst under the influence of CXM.

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Delayed-onset amnesia caused by protein synthesis inhibition in odor-taste associative memory of the terrestrial slug Limax valentianus
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The terrestrial slug Limax avoids the odor of innately preferred food after it is presented with the aversive taste of quinidine. This type of associative memory persists for several weeks. We investigated effects of protein synthesis inhibitors on the retention of this odor–taste associative memory. Anisomycin or cycloheximide applied to the slug 30 min prior to conditioning impaired the memory retention as late as two or more days after the conditioning, while the retention of a short-term memory was normal for up to 24 h. In contrast, the inhibition of protein synthesis by these inhibitors decays within several hours. In Limax, the onset of amnesia is unusually delayed when protein synthesis is suppressed at the time of conditioning.
Conditioned taste aversion as a learning and memory paradigm
2001, Behavioural Brain Research
Conditioned taste aversion (CTA) is a well established learning and memory paradigm in rats and mice that is considered to be a special form of classical conditioning. Rodents — as well as many other species including man — learn to associate a novel taste (CS) with nausea (US), and as a consequence avoid drinking fluid with this specific taste. In contrast to other types of classical conditioning, even CS–US intervals lasting several hours lead to an aversion to the gustatory CS. With increasing CS–US delay duration, however, the aversion against the CS gradually decreases. Mice differ from rats in their reaction to the CS as well as the US. They tolerate a much higher concentration of saccharin and they do not show any clear signs of nausea when injected with the US. Advantages of this task are its relative independence of motor behavior, well described pathways for the CS and partly the US, and the wealth of available anatomical and pharmacological data implying several brain structures (e.g. parabrachial nucleus, amygdala, insular cortex), neurotransmitters and their receptors (e.g. cholinergic system, NMDA-receptors), and cellular processes (e.g. expression of immediate early genes, Ras–MAP kinase signaling pathway, CREB phosphorilation, protein tyrosine phosphorilation, protein synthesis) in CTA. The CTA paradigm has also been successfully used to phenotype mouse mutants.
Dynamics of c-fos and ICER mRNA expression in rat forebrain following lithium chloride injection
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Lithium is commonly used as a treatment for affective disorders in humans and as a toxin to produce conditioned taste aversions in rats. LiCl administration in rats has been correlated with activation of c-fos and cAMP-mediated gene transcription in many brain regions; however, little is known about the timing or duration of gene activation. We hypothesized that c-fos gene transcription is rapidly stimulated by LiCl, followed later by the expression of the inducible cAMP early repressor (ICER) transcription factor, a negative modulator of cAMP-mediated gene transcription. By in situ hybridization, we analyzed the timecourse of c-fos and ICER mRNA expression in the central nucleus of the amygdala (CeA), the paraventricular nucleus of the hypothalamus (PVN) and the supraoptic nucleus (SON) at seven time points (0, 0.3, 1, 3, 6, 9 and 12 h) after intraperitoneal LiCl injection (0.15 M, 12 ml/kg, 76 mg/kg). Expression of c-fos mRNA peaked between 20 min and 1 h and returned to baseline by 3 h in the CeA, PVN and SON. ICER mRNA was detected in these regions at 20 min, peaked at 1–3 h and returned to nearly baseline 9 h following LiCl injection. The time lag between c-fos mRNA expression and ICER mRNA expression within the same regions is consistent with ICER terminating c-fos gene transcription. However, no refractory period was detected for restimulation of c-fos transcription by a second injection of LiCl during the period of peak ICER mRNA expression, suggesting the involvement of other transcriptional modulators.
Molecular neurobiology of ingestive behavior
2000, Nutrition
The concepts and tools of molecular biology may be applied to almost any component of the animal involved in ingestion, but two categories of model system are particularly relevant for molecular analysis: homeostatic regulation of neuropeptide expression in the hypothalamus and neuronal plasticity underlying persistent changes in ingestive behavior. Molecular approaches to these models are reviewed, focusing on our strategy for analyzing conditioned taste aversion learning. Three questions must be answered: Where do the long-term changes occur within the distributed neural network that mediates feeding? This answer reveals the site of neuronal restructuring mediated by gene expression. When does the transition occur from short-term expression to long-term persistence of the change in behavior? This transition reveals the critical time of gene expression. What genes are expressed during the change in behavior? The expression of thousands of genes in discrete subpopulations of cells is likely to be required during critical periods of neuronal restructuring. The identification of these genes is a general challenge for molecular neurobiology. The analysis of ingestive behavior can profit from molecular tools, but ingestion also provides informative models that elucidate the principles of time- and neuron-specific gene expression mediating complex behaviors.
Investigations into the neuropharmacological basis of temporal stages of memory formation in mice trained in an active avoidance task
1987, Behavioural Brain Research
The memorial effects of glutamate, LaCl₃, ouabain, or anisomycin injection around the time of active avoidance training in mice were assessed in this study. Based on the Gibbs and Ng hypothesis of memory formation in chicks (Biobehav. Rev., 1 [1977] 113–136), it was predicted that these pharmacological agents would not only induce significant amnesia but, more specifically, short duration memory should be selectively impaired by glutamate and LaCl₃, intermediate duration memory should be impaired by ouabain, and anisomycin should affect only long-lasting memories. Results of the experiments described below indicate these drugs are potent inhibitors of memory formation in rodents. In addition, LaCl₃-induced amnesia was fully prevented by CaCl₂. However, the mechanism by which glutamate and ouabain affected memory may not be exactly as described by Gibbs and Ng: γ-d-glutamylglycine and diphenylhydantoin did not completely prevent glutamate- and ouabain-induced amnesias, respectively. Finally, all amnestic agents induced amnesia that developed within minutes of training, and the time course of development of amnesia for each drug could not be distinguished from one another. These data are discussed in terms of their implications for the Gibbs and Ng model of memory formation.
Protein synthesis inhibition and amnesia for saccharin aversion memory in rats after intra-cisternal administration of cycloheximide
1982, Physiology and Behavior
The series of experiments reported further investigated the time course relationship of the amnesia for saccharin aversion memory in rats and the inhibition of protein synthesis resulting from cycloheximide (CXM). The first experiment showed that intraventricular CXM injected rats which had been trained 7 hrs after injection had learned the contingency under a considerable inhibition of protein synthesis. However, 1 hr after CXM injection protein synthesis inhibition was 86% and yet there was no amnesia observed 24 hr after training. It was also apparent that there were no marked regional differences in the extent of protein synthesis inhibition after intraventricular CXM. Finally, intracisternal injection of CXM 1 hr before training resulted in amnesia 24 hrs after training although this effect was greater when the injection was performed 7 hr before training. The findings (1) are consistent with Day et al's [4] suggestion of maximal protein synthesis inhibition at 1 hr post CXM injection with an approximately linear decline thereafter, and (2) provide no support for the involvement of the brain stem nucleus solitarius in taste aversion learning.

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¹: Reprint requests should be addressed to Dr. A. Tucker

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Cycloheximide-induced amnesia for taste aversion memory in rats

Abstract

Brain Res.

Physiol. Behav.

Physiol. Behav.

Life Sci.

Physiol. Behav.

Delayed and sustained effect of acetoxycycloheximide on memory in mice

Arousal and the conversion of “short-term” to “long-term” memory

Protein synthesis and memory