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Expression of the CS- and US-pre-exposure effects in the conditioned taste aversion paradigm and their abolition following systemic amphetamine treatment in C57BL6/J mice.

In classical conditioning, pre-exposures to either the to-be-conditioned stimulus (CS) or unconditioned stimulus (US) can retard subsequent conditioning between the CS and US. The present experiment evaluated the expression of these two pre-exposure effects in mice of the C57BL6/J strain, one of the most common background strains for genetically altered mice. We tested whether their expression would be disrupted by amphetamine treatment (2.5 mg/kg, i.p.) in a conditioned taste aversion paradigm with sucrose as the CS and lithium chloride-induced gastric malaise as the US. We found that one pre-exposure (PE) to either the CS or the US reduced aversion to sucrose solution in the controls following conditioning, but no such tendency was evident in the amphetamine-treated mice. The present study represents the first report of amphetamine-induced disruption of the CS-PE effect (ie latent inhibition) in mice, and the first attempt to compare it directly with the US-PE effect in any species. It extended previous reports in rats and humans, suggesting that the sensitivity of latent inhibition to amphetamine is largely comparable across species, thereby lending credence to the use of the latent inhibition effect as a behavioral assay for psychotic-like phenotype in transgenic mice. The parallel observation in the US-PE effect further indicates that its expression, at least in the present conditioned taste aversion paradigm, may also be under similar influence of the dopaminergic system.

Amphetamine↗

Corticotrophin-releasing factor produces a long-lasting enhancement of synaptic efficacy in the hippocampus.

We have previously demonstrated that intra-hippocampal injection of corticotrophin-releasing factor improved memory retention of an inhibitory avoidance learning in rats; while the electrophysiological effects corticotrophin-releasing factor produces on hippocampal neurons are largely uncharacterized. In the present study, we found that corticotrophin-releasing factor injected into the dentate gyrus of hippocampus produced a dose-dependent and long-lasting enhancement in synaptic efficacy of these neurons, as measured by an increase in the amplitude and slope of population excitatory postsynaptic potentials, as well as the amplitude of population spike. The onset of corticotrophin-releasing factor-induced potentiation was slow. It was observed approximately 40-60 min after corticotrophin-releasing factor administration and lasted for more than 5 h. This effect of corticotrophin-releasing factor was blocked by pretreatment with the cyclase-adenosine-3,5-monophosphate (cAMP) inhibitor Rp-adenosine-3,5-cyclic monophosphothiolate triethylamine (Rp-cAMPS) and partially blocked by the N-methyl-D-aspartate receptor antagonist MK-801. Further, pretreatment with corticotrophin-releasing factor receptor antagonist dose-dependently diminished tetanization-induced long-term potentiation, and corticotrophin-releasing factor and tetanic stimuli had an additive effect on hippocampal neuron excitation. Moreover, direct injection of corticotrophin-releasing factor increased cAMP level in the dentate gyrus. These results together suggest that corticotrophin-releasing factor-induced potentiation simulates the late phase of tetanization-induced long-term potentiation and cAMP seems to be the messenger mediating this effect. Moreover, corticotrophin-releasing factor-induced potentiation and long-term potentiation may share some similar mechanisms, and corticotrophin-releasing factor is probably involved in the neural circuits underlying long-term potentiation. Thus, corticotrophin-releasing factor may play an important role in modulating synaptic plasticity in the hippocampus.

Action Potentials↗

Neurotrophic and neuroprotective actions of ginsenosides Rb(1) and Rg(1).

The ginsenosides have many pharmacological actions, including various actions on the nervous system. Our previous studies have demonstrated that two ginsenosides, Rb(1) and Rg(1) improve performance in a passive avoidance-learning paradigm and enhance cholinergic metabolism. The present study was designed to examine the cellular neurotrophic and neuroprotective actions of two pure ginsenosides in two model systems. PC12 cells were grown in the absence or presence of nerve growth factor (NGF) as a positive control, and different concentrations of Rb(1) or Rg(1). To assess neurotrophic properties, neurite outgrowth was quantified for representative fields of cells. After 8 days in culture, both ginsenosides enhanced neurite outgrowth in the presence of a sub-optimal dose of (2 ng/ml) NGF, but did not significantly stimulate neurite outgrowth in the absence of NGF. However, after 18 days in culture, both ginsenosides increased neurite outgrowth in the absence of NGF. SN-K-SH cells were grown in the absence or presence of MPTP or beta-amyloid to assess neuroprotection. Rb(1) and Rg(1) both reversed MPTP-induced cell death. beta-Amyloid-induced cell death was not reversed by either ginsenoside, but Rg(1) produced a modest enhancement of cell death in this model. These results suggest that these two ginsenosides have neurotrophic and selective neuroprotective actions that may contribute to the purported enhancement of cognitive function.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

A requirement for memory retrieval during and after long-term extinction learning.

Current learning theories are based on the idea that learning is driven by the difference between expectations and experience (the delta rule). In extinction, one learns that certain expectations no longer apply. Here, we test the potential validity of the delta rule by manipulating memory retrieval (and thus expectations) during extinction learning. Adrenergic signaling is critical for the time-limited retrieval (but not acquisition or consolidation) of contextual fear. Using genetic and pharmacologic approaches to manipulate adrenergic signaling, we find that long-term extinction requires memory retrieval but not conditioned responding. Identical manipulations of the adrenergic system that do not affect memory retrieval do not alter extinction. The results provide substantial support for the delta rule of learning theory. In addition, the timing over which extinction is sensitive to adrenergic manipulation suggests a model whereby memory retrieval occurs during, and several hours after, extinction learning to consolidate long-term extinction memory.

Animals↗

Effectiveness of the defence mechanism of the turnip sawfly, Athalia rosae (Hymenoptera: Tenthredinidae), against predation by lizards.

The turnip sawfly, Athalia rosae Linnaeus, is a pest on cruciferous crops. Larvae sequester secondary plant compounds, namely glucosinolates, in their haemolymph. When attacked, their integument is easily disrupted and a droplet of haemolymph is exuded ('easy bleeding'). This has been shown to be an effective, chemical-based, defence against invertebrate predators. The efficiency of this proposed defence was tested against a vertebrate predator, using groups of the iguanid lizard Anolis carolinensis Voigt as a model predator. Caterpillars of Pieris rapae Linnaeus and Pieris brassicae Linnaeus served as control prey species that do not sequester glucosinolates. Lizards attacked far fewer sawfly larvae than pierid caterpillars. Several of the sawfly larvae were rejected after an initial attack, demonstrating unpalatability to the lizards, while the Pieris larvae were not rejected. However, P. rapae larvae topically treated with extracts of haemolymph of A. rosae had no deterrent effect on the lizards and no avoidance learning occurred over a period of two weeks. Adult sawflies do not easy bleed but have glucosinolates carried over from the larval stage. Lizards attacked them at a higher rate than larvae and they were never rejected. The results suggest that for the defensive effectiveness of the pest sawfly species against vertebrates the chemical cue is not necessarily sufficient. Movement and colour may be important additional factors triggering the behaviour of vertebrate predators.

Adaptation, Physiological↗

The CS-preexposure effect in conditioned taste-aversion learning in golden hamsters.

In Experiment 1, golden hamsters were injected with either 0.9% saline or the nausea-inducing agent, lithium chloride (LiCL), immediately after consuming a flavored diet that was either novel or familiar. The LiCl-induced aversion was strong in hamsters for which the flavored diet was novel, but no significant aversion was observed in hamsters that were familiar with the flavored diet. In Experiment 2, the strength of the LiCl-induced aversion was related inversely to the amount of conditioned-stimulus (CS) preexposure and directly to the duration of the preexposure-conditioning interval. Thus, although some previous researchers have suggested that hamsters may not demonstrate the CS-preexposure effect in a conditioned taste-aversion paradigm, they clearly did so under the conditions of the present experiments, and moreover, the characteristics of the CS-preexposure effect in hamsters were generally similar to those observed in rats.

Animals↗

Danger at the waterhole.

The effects of declining accessibility of water and risk of electric shock on drinking patterns in rats were examined. Rats chose between two conditions to obtain their daily intake of water. In one condition, accessibility of water decreased systematically. In the other condition, water was readily accessible, but responses occasionally were followed by electric shock. Both variables affected drinking patterns similarly. As accessibility to water decreased, the number of drinking bouts initiated decreased but the quantity of water consumed increased. In response to risk of electric shock, the number of drinking bouts decreased but bout size increased. Results are considered in light of findings by Fanselow, Lester, and Helmstetter, (1988), Collier, Hirsch, and Hamlin (1972), and Marwine and Collier (1979).

Animals↗

Taste aversion after ingestion of lithium chloride: an associative analysis.

In five experiments with rats we examined the aversion established by consumption of a solution of lithium chloride (LiCl). Experiment 1 showed that consumption of LiCl established an aversion to saline (NaCl). Experiment 2 showed that the size of the aversion was reduced in rats given pre-exposure to saline (a latent inhibition effect). Experiment 3 showed that experience of a sucrose-saline compound prior to consumption of LiCl generated an aversion to sucrose (a sensory preconditioning effect). Experiments 4 and 5 examined the effects produced by consumption of a sucrose-LiCl compound and demonstrated reciprocal overshadowing between the two tastes. These results confirm that consumption of LiCl establishes an aversion to the taste of this substance. Their implications for the use of orally consumed LiCl as a technique for the control of predatory behaviour are discussed.

Animals↗

The role of injection cues in the associative control of the US pre-exposure effect in flavour aversion learning.

Two experiments, using rats as subjects, examined the role of contextual cues in producing the unconditioned stimulus (US) pre-exposure effect in conditioned taste aversion. Experiment 1 showed a significant US pre-exposure effect, when the pre-exposure was conducted in a familiar context, and that a change of context between the pre-exposure and conditioning phases did not attenuate this effect. Experiment 2 demonstrated that extinction of injection-related cues after the pre-exposure stage attenuated the US pre-exposure effect, when the pre-exposure was conducted in either a familiar or a novel context. Taken together, these results support the associative explanation of the US pre-exposure effect in terms of blocking, incorporating a role for injection-related cues in the context blocking analysis of the US pre-exposure effect.

Animals↗

Depression of an instrumental response by a single devaluation of its outcome.

In three experiments rats were trained to make two different instrumental responses for different outcomes. Then the outcomes were given a single differential conditioning experience with lithium chloride. That differential treatment was sufficient to produce differential instrumental responding in a subsequent test. Re-exposure to the devalued outcome was not necessary for an impact on instrumental performance.

Animals↗

Brain mitochondrial aldehyde dehydrogenase: relation to acetaldehyde aversion in low-alcohol-drinking (UChA) and high-alcohol-drinking (UChB) rats.

Previous reports indicate that the low-drinker (UChA) rats, when compared to high-drinker (UChB) rats, display lower mitochondrial aldehyde dehydrogenase (ALDH2) activity due to a mutation of the Aldh2 gene. Because a later study found line differences in sensitivity to the aversive effects of acetaldehyde (AcH) administered intraperitoneally (i.p.), which were not associated with the line difference detected in blood AcH levels, the present study examined the contribution of brain ALDH2 activity to AcH aversion in UChA and UChB rats. In experiment 1, we established the dose - response curves for AcH aversion (25, 50 or 100 mg/kg i.p.) in rats of both lines by using a conditioned taste aversion (CTA) paradigm. The results confirm our previous finding that UChA and UChB rats presented marked differences in their AcH aversion thresholds, which were not associated with the line differences detected in blood AcH levels. In experiment 2, the possibility that the inhibition of the brain ALDH2 would lower the AcH aversion threshold in both lines was studied by determining the effect of cyanamide (10 mg/kg i.p.) pretreatment, an inhibitor of ALDH, on AcH aversion, blood AcH levels and brain ALDH2 activity. The finding that blocking the brain ALDH2 (52%) by cyanamide can make a non-aversive dose of AcH (25 mg/kg) aversive to UChA and UChB rats at blood AcH levels comparable to those induced by a non-aversive dose of AcH (100 mg/kg) in control UChB rats indicates that the line difference in AcH aversion is associated more with brain ALDH2 activity than with liver ALDH2 activity.

Acetaldehyde↗

Effects on the development of offspring of female mice exposed to platinum sulfate or sodium hexachloroplatinate during pregnancy or lactation.

On d 7 or 12 of gestation or on d 2 postpartum, Swiss ICR dams were administered either (1) a single intragastric dose of Pt(SO4) at the LD1 level or dilute H2SO4 at an equivalent volume, pH, and sulfate content, or (2) a single subcutaneous dose of Na2PtCl6 or phosphate-buffered saline at an equivalent volume and pH. To differentiate prenatal from postnatal effects of the compounds on the offspring, a full cross-fostering design was employed. Rate of growth (as a function of weight gain) and gross activity of the neonates were assessed on d 8 or 13 postpartum. On d 60-65 postpartum, open-field behavior (ambulations and rearings), rotarod performance, and passive avoidance learning of the adult offspring were investigated. Exposure to Pt(SO4)2 resulted in reduced offspring weight from d 8 to 45 postpartum, whereas the major effect of Na2PtCl6 was a reduction in activity level of the offspring of mothers exposed on d 12 of gestation.

Analysis of Variance↗

Limitations on representation-mediated potentiation of flavour or odour aversions.

Odour aversion learning is often potentiated in the presence of flavour stimuli. Establishment of an aversion to an odour is greater when an odour + flavour compound is paired with illness than when the odour alone is paired with illness. Holland (1983) showed that under some circumstances auditory or olfactory stimuli previously paired with flavours may also potentiate odour aversion learning. The present experiments examined limitations on this representation-mediated potentiation of aversion learning. The results indicated that conditioned stimuli (CSs) that activate representations of potentiating cues are themselves immune to potentiation by other CS-activated representations, but remain susceptible to potentiation by their real stimulus associates.

Animals↗

Mediated conditioning and retrospective revaluation with LiCl then flavour pairings.

It is becoming accepted that the associative strength of a cue can change in its absence, despite this being difficult to explain using existing theories of Pavlovian conditioning. To investigate the influence of timing on learning about the representation of an absent cue, lithium chloride (LiCl) or a flavour previously paired with LiCl was presented in a distinctive context that had previously been paired with a neutral target flavour. The former treatment produced an aversion to the target flavour whether the LiCl was presented 10 min before, or immediately after, exposure to the context. However, presenting the flavour associate of LiCl created an aversion to the target flavour only if it had been presented 10 min after LiCl during initial training. This pattern of results cannot be explained in the terms of a simple timing account, and it is proposed that an explanation will require different associative rules operating in simultaneous and successive training schedules.

Animals↗