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PubMed1983

Odor-aversion learning by rats following LiCl exposure: ontogenetic influences.

The influence of LiCl preexposure on odor-aversion conditioning produced by an odor-LiCl pairing was studied in rats 7-31 days old. LiCl preexposure interfered with the acquisition of the odor aversion in both young and old pups. The time course of this effect depended, however, on the age of the pups. It lasted much longer (over 24 hr) if pups 8-17 days old were preexposed to LiCl than if the pups were preexposed when 30 days old (less 12 hr). Alternative interpretations of these data were discussed, and it was suggested that the age-dependent differences in the time course of the LiCl preexposed effect may be determined in part by age-related differences in the rat's excretory processes that clear lithium from the circulatory system.

Aging↗

PubMed1984

Conditioning of aversion to an odor paired with peripheral shock in the developing rat.

Four experiments examined an apparent inability to associate, or severe deficiency in associating, an odor and a footshock during the first 2 weeks of life in the rat, a cue-to-consequence relationship that had formerly seemed age-dependent. With a particular classical conditioning procedure, however, significant conditioning occurred on postnatal Days 6 and 10 with relatively few conditioning trials; the procedure employed an odor explicitly unpaired with footshock (CS-), as well as an odor paired with footshock (CS+) (Experiment I). Experiment II assessed the contribution of a CS- exposure in the conditioning of rats 8, 15, or 50 days of age. For 8-day-olds, exposure to both the CS+ and CS- resulted in conditioned aversion to the CS+ after eight but not one conditioning trials, but neither 1 nor eight trials with only a CS+ produced conditioning. For 15- and 50-day-olds, conditioning to the CS+ odor was significant after one trial with, but not without, a specific CS-; with eight trials, however, conditioning was significant with or without the specific CS-. It was verified with the 50-day-olds in Experiment III that aversion to the CS+ was conditioned with a single trial only if a CS- had been presented, with a slight trend toward superior conditioning if the CS- preceded rather than followed the CS+ during conditioning. Experiment IV tested the hypothesis that exposure to the distinctive CS- odor sensitizes the animal to the specific properties of the CS+ odor. Fifteen and 50-day-old rats were given one conditioning trial with a CS+ odor that was either unaccompanied by a CS- or that was presented with a CS- odor in the same context as the CS+ or in a different context. For both 15- and 50-day-old rats, conditioning to the CS+ occurred only for animals given the CS- in the same context as the CS+, indicating that the hypothesis should be rejected. The results generally indicate rapid and substantial odor-footshock conditioning in rats as young as 6 days of age, with CS- exposure established as perhaps especially significant for conditioning early in life, but important for rats of all ages tested, from infancy to adulthood.

Aging↗

PubMed1984

A specialization of taste aversion learning during suckling and its weaning-associated transformation.

During ontogenesis, altricial mammals advance through different ecological niches which require correspondingly different adaptive strategies. We view learning as an important feature of ontogenetic adaptations and consider the acquisition and expression of taste aversion learning during nursing within this framework. Fifteen-day-old preweanling rat pups fail to acquire conditioned taste aversions while nursing, whereas 20-day-old weanlings readily learn flavor aversions while suckling (Martin & Alberts, 1979). The developmental emergence of taste aversion learning while nursing coincides with reduction in maternal milk supply and the rat pup's transition to a solid food diet. We considered the ontogenetic transformation of learning while nursing as a feeding-related adaptive strategy of the weanling rat and tested two predictions derived from this view: (1) delayed weaning might postpone acquisition or expression of suckling-related taste aversions and (2) conditions that permit weaning (e.g., access to alternate food sources) might induce acquisition or expression of such taste aversions. Both predictions were confirmed.

Animals↗

PubMed1986

Conditioning of aversion to alcohol orosensory cues in 5- and 10-day rats: subsequent reduction in alcohol ingestion.

Two experiments examined in 5- and 10-day-old rat pups the impact of alcohol olfactory aversions upon subsequent alcohol intake. In Experiment 1 it was observed that at both ages, animals given a single pairing of alcohol odor and LiCl subsequently consumed less alcohol than those in any of 4 control conditions (alcohol odor unpaired with LiCl, alcohol odor exposure, lemon odor paired with LiCl, and untreated animals). In Experiment 2, pups of both age groups were given LiCl following exposure to alcohol odor, the infusion of an alcohol solution or both stimuli simultaneously. Rats given explicitly unpaired presentations of the different conditioned stimuli and internal malaise served as controls. It was observed that equivalent aversions to alcohol ingestion were expressed whether the infants had experienced the alcohol odor, the alcohol infusion, or both, paired with toxicosis. These experiments extend the ontogenetic spectrum of circumstances in which olfactory experiences affect subsequent ethanol ingestion and also may indicate an early nondifferentiated processing of odorant and gustatory cues arising from an ethanol stimulus.

Aging↗

PubMed1989

Ontogenetic differences in short-term retention of Pavlovian conditioning.

In the present series of studies 16- and 21-day-old rats acquired an aversion to a black compartment (CS+) paired with footshock, only if given preconditioning exposure to a white chamber (CS-) not paired with footshock. The strength of conditioning was inversely related to the length of the retention interval in both age groups. However, the rate of forgetting was accelerated in the 16-day-old subjects, indicating infantile amnesia for the conditioned aversion. Strength of conditioning was also inversely related to the length of the CS-/CS+ interval in both age groups, indicating that expression of the aversion is critically dependent on an active memory of the CS- at the time of conditioning. Additionally, there was an ontogenetic decrease in the rate of forgetting of the CS-, indicating infantile amnesia for elements of the conditioning episode that did not predict occurrence of US.

Aging↗

PubMed1992

The biphasic effect of morphine on odor conditioning in neonatal rats.

Three experiments examined the dose-dependent biphasic effect of morphine on odor conditioning in neonatal rats. In Experiment 1, a single pairing of an odor and a low dose of morphine (0.5 mg/kg) in 5-day-old rats produced an odor preference, relative to an unpaired control group. In Experiment 2, pairing an odor with a high dose of morphine (2.0 mg/kg) produced an odor aversion, relative to an unpaired control group. A third experiment compared performance of a group given odor and morphine (2.0 mg/kg) paired to that of two unpaired groups: one given morphine 24 hr prior to and the other 24 hr after odor exposure. The paired group showed an odor aversion relative to both of the unpaired groups, which did not differ. The latter finding suggests that even if morphine metabolism is incomplete after 24 hr, behavior is unaffected. These results are discussed in reference to the functional development of the opioid system in rats.

Aging↗

PubMed2004

Consolidation of CS and US representations in associative fear conditioning.

Much attention has been paid to the associative processes that are necessary to fuse together representations of the various components of an episodic memory. In the present study, we focus on the processes involved in the formation of lasting representations of the individual components that make up a fear-conditioning episode. In one-trial contextual fear conditioning experiments, weak conditioning to context occurs if the shock is delivered immediately following placement of the animal in a novel conditioning apparatus, a phenomenon known as the immediate shock deficit. We show that the immediate shock deficit in mice may be alleviated by pre-exposure to either the context or shock. In using this approach to temporally dissect a contextual fear-conditioning task into its constituent representational and associative processes, we are able to examine directly the processes that are important for formation of lasting representations of the context conditioned stimulus (CS) or unconditioned stimulus (US). Our data indicate that the formation of a lasting representation of the context or shock engages protein synthesis-dependent processes. Furthermore, genetic disruption of cAMP-responsive element binding protein (CREB), a transcription factor that regulates the synthesis of new proteins required for long-term memory, disrupts the formation of lasting context memories. We go on to show that the stress hormone epinephrine modulates the consolidation of a context memory, and reverses consolidation deficits in the CREB-deficient mice. Finally we show that disrupting either NMDA or calcium/calmodulin-dependent kinase II (CaMKII) function impairs consolidation of context memories. Together, these data suggest that this approach is particularly suited for the characterization of molecular and cellular processes underlying the formation of stimulus representations.

Animals↗

PubMed1991

Swimming navigation and structural variations of the infrapyramidal mossy fibers in the hippocampus of the mouse.

The extent of the infrapyramidal mossy fiber projection in CA3 (IIP-MF) at the midseptotemporal level correlates negatively with two-way avoidance learning and positively with performance in the radial maze, both tasks known to be sensitive to hippocampal lesions. If hippocampal structural variations are causing behavioral variations, one must predict positive correlations between the extent of the IIP-MF and performance in swimming navigation. Thus, the authors studied learning and reversal learning of swimming navigation in mice in which the size of the IIP-MF had been randomized by means of systematic crosses and in 2 mouse strains known for differential infrapyramidal projections (C57BL/6 and DBA/2). In 19 random-bred mice (9 male, 10 female), the extent of the IIP-MF showed negative correlations with swimming time after platform reversal (day 4: r = -0.50, P < .03; day 5 r = -0.73, P < .001), but none during acquisition of the task. In addition, statistical analysis suggested an influence of asymmetrically distributed mossy fiber projections during reversal learning. The strain comparison between 18 DBA/2 and 16 C57BL/6 male mice confirmed these results: no strain difference during days 1-3, and a significantly faster swimming time in the strain C57BL/6 (with large IIP-MF) at day 5 (second day of reversal), associated with significantly more crossings of the former platform location during the early phases of reversal learning. This latter measure was also negatively correlated with asymmetry of the IIP-MF in both strains. Finally, variations of the IIP-MF were correlated partially with adjustment of swimming speed that appeared to depend on size and asymmetry of CA4 as well. Thus, natural variations in the size of the IIP-MF distribution, and, perhaps, of CA4, appear to linearly influence processes directly involved in complex spatial learning.

Animals↗

PubMed1995

Chronically administered 3-nitropropionic acid produces selective lesions in the striatum and reduces muscle tonus.

Systemically administered 3-nitropropionic acid (3- NPA), irreversible inhibitor of succinate dehydrogenase, produced characteristic bilateral lesions in the striatum (STR) in the rat. Inside the lesion, neutrophils invaded and strong immunoreaction for IgG as well as complement factor C3b/C4b receptor (C3b/C4br) were observed. The core of the lesion lost the immunoreaction for glial fibrillary acidic protein (GFAP) while the marginal area had abundant GFAP-labeled astrocytes around the vessels. Intoxicated rats often became somnolent and were awkward in cooperative movement on a pole climbing test, but they had a quite good memory retention in a passive avoidance learning. Muscle tonus in some of the intoxicated rats became hypotonic with low voltage electromyogram (EMG) activity, especially in lower limbs. In summary, 3-NPA intoxicated rats had selective bilateral lesions in the STR and exhibited disturbances in a cooperative movement owing to the impairment in muscle tonus, thus it would be a useful animal model to deduce the central pathogenesis of Huntington's disease.

Animals↗

PubMed1992

Nerve growth factor and choline acetyltransferase activity levels in the rat brain following experimental impairment of cerebral glucose and energy metabolism.

Intracerebroventricular (ICV) injection of streptozotocin (STZ) has been reported to impair cerebral glucose utilization and energy metabolism (Nitsch and Hoyer: Neurosci Lett, 128:199-202, 1991) and also to prejudice passive avoidance learning in adult rats (Mayer et al.: Brain Res 532:95-100, 1990). It is well established that the forebrain cholinergic system, whose integrity is essential for learning and memory functions, depends on the target-derived retrograde messenger nerve growth factor (NGF). Therefore, we measured NGF and choline acetyltransferase (ChAT) activity levels in the forebrain cholinergic system in adult rats that had received a single injection of either STZ or artificial cerebrospinal fluid into the left ventricle 1 or 3 weeks prior to sacrifice. One week after ICV STZ treatment, NGF content was significantly decreased (-32%) in the septal region, where NGF-responsive cell bodies are located and NGF exerts its neurotrophic action after retrograde transport from NGF-producing targets. In contrast, NGF levels in the cortex and hippocampus, which are target regions for the basal forebrain cholinergic neurons, and in the brainstem and cerebellum were increased (+12% to +47%) within 3 weeks after ICV STZ treatment. The alterations in NGF levels were not related to changes in ChAT activity that decreased in the hippocampus by only 15%. This might be due to masking effects exerted by compensatory NGF-mediated stimulation of ChAT activity in remaining functional neurons. It is suggested that impaired behavior which has been observed after STZ-induced impairment of cerebral glucose and energy metabolism may be at least partially related to a diminished capacity of central NGF-responsive neurons to bind and/or transport NGF.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1996

Effect of age and caloric intake on protein oxidation in different brain regions and on behavioral functions of the mouse.

The objective of this study was to determine if oxidative stress/damage is a possible causal factor in the senescence-related loss of brain functions in the mouse. If such a relationship indeed existed, it was expected that oxidative protein damage would increase with age within regions of the brain associated with senescence-related functional loss, and that calorie restriction, an intervention which retards certain aspects of age-associated functional loss, would reverse such increases. Dietary restriction was found to retard age-associated decline of sensorimotor coordination and improve performance of aged mice on an avoidance learning problem. Protein carbonyl concentration, one measure of protein oxidation, increased from 8 to 27 months of age in most regions of the mouse brain, with the most notable increases occurring in the striatum and hippocampus, regions of the brain strongly implicated in age-associated functional loss. Age-associated loss of protein sulfhydryls was more uniform across brain regions and did not involve the hippocampus. Dietary restriction resulted in reversal of the age-associated regional trends in carbonyl and sulfhydryl concentration, with the largest changes occurring within the striatum. Cross over studies in aged calorie restricted and ad libitum fed mice indicated that lowering of carbonyl content by calorie restriction could be induced or reversed within a time frame of 3 to 6 weeks. These findings suggest that the beneficial effects of dietary restriction upon brain function and life span may depend upon its ability to acutely reduce steady-state levels of oxidative stress.

Aging↗

PubMed2001

Can receiver psychology explain the evolution of aposematism?

The evolution of aposematism is difficult to explain because: (1) new aposematic morphs will be relatively rare and thus risk extinction during predator education; and (2) aposematic morphs lack the protection of crypsis, and thus appear to invite attacks. I describe a simple method for evaluating whether rare aposematic morphs may be selectively advantaged by their effects on predator psychologies. Using a simulated virtual predator, I consider the advantages that might accrue to dispersed and aggregated morphs if aposematic prey can cause neophobic avoidance, accelerate avoidance learning and decelerate predator forgetting. Simulations show that aposematism is very hard to explain unless there are particular combinations of ecological and psychological factors. If prey are dispersed throughout a locality then aposematism will be favoured only if (1) there is neophobia, learning effects and forgetting or if (2) there are learning effects and warning signals reduce forgetting rates. However, the best scenario for aposematic advantage involves learning rates, forgetting and neophobia when prey are aggregated. Prey aggregation has two important effects. First, it is a highly effective way to maximize the per capita benefits of the neophobia. Second, after an attack on a single prey the benefits of learnt aversions will be immediately conferred on the surviving members of an aggregation without the diluting effects of forgetting. Aggregation therefore provides good protection against forgetting. The simulations thus provide new insights into the complexities of aposematic protection and suggest some important directions for empirical work. Copyright 2001 The Association for the Study of Animal Behaviour.

Journal Article↗

PubMed1995

Scopolamine selectively disrupts the acquisition of contextual fear conditioning in rats.

Muscarinic cholinergic antagonism produces learning and memory deficits in a variety of hippocampal-dependent tasks. Hippocampal lesions produce both acquisition deficits and retrograde amnesia for contextual fear conditioning, but do not impact fear conditioning to discrete cues. In order to examine the effects of muscarinic antagonism in this paradigm, rats were given scopolamine (1 mg/kg) either before or for 3 days after a Pavlovian fear-conditioning session in which tones were paired with aversive footshocks. Fear to the context and the tone was assessed by measuring freezing in separate tests. It ws found that pretraining, but not posttraining, scopolamine severely impaired contextual fear conditioning; tone conditioning was not affected under either condition (cf., Young, Bohenek, & Fanselow, Neurobiology of Learning and Memory, 63, 174-180, 1995).

Animals↗

PubMed1995

The influence of flavored solution concentration on the poisoned-partner effect.

Two experiments are reported in which we attempted to replicate the poisoned-partner effect, varying the concentration of a novel-tasting solution. Unpoisoned rats exhibited an aversion to a saccharin solution that had been consumed previously in the presence of a poisoned rat when it had a concentration of 0.6% but did not when it was of 0.15%. These results seem to show that the poisoned-partner effect depends upon the intensity of the solution employed and to suggest that it may be facilitated by a low initial consumption.

Animals↗

PubMed1995

Latent inhibition in conditioned taste aversion: the roles of stimulus frequency and duration and the amount of fluid ingested during preexposure.

Two experiments examined the effects of total stimulus preexposure on latent inhibition (LI) in a conditioned taste aversion procedure with rats. Experiment 1 varied the frequency and duration of saccharin preexposures. LI was an increasing function of the product of frequency x duration. Experiment 2 kept saccharin exposure time constant but varied the amount of saccharin consumed by manipulating number of hours of fluid deprivation prior to exposure. Deprivation schedule conditions affected the amounts consumed which, in turn, modulated LI magnitude, at least with a 1-day acquisition-test interval, as in Experiment 1. The data clearly indicate that LI is a function of total amount of contact with the preexposed saccharin solution. In addition, half of the subjects in Experiment 2 were tested 21 days after the conditioning event. LI was not present in any group tested at this interval. These data were discussed in regard to the controversy regarding whether LI represents a failure to acquire the CS-US association or a failure to retrieve that association.

Animals↗

PubMed1995

Neuroanatomical and functional specificity of the basolateral amygdaloid nucleus in taste-potentiated odor aversion.

The present study aimed at documenting the neurobiological substrate of taste-potentiated odor aversion (TPOA) in the rat. The role of several temporal lobe structures in discriminative TPOA learning was questioned. The effects of excitotoxic lesions (ibotenate) of the basolateral amygdaloid nucleus, the central amygdaloid nucleus, the caudate putamen nucleus, and aspirative lesion of the entorhinal cortex were studied. The results show that only basolateral amygdaloid nucleus (ABL) damage impaired TPOA. This effect was selective of TPOA, since it spared conditioned taste aversion (CTA) and olfactory perception. In order to find out which process in TPOA requires normal functioning of the ABL, the effects of microinjections of a GABAA agonist (muscimol) into the ABL at various stages of the experiment were examined. The results show that application of muscimol during the acquisition, before or after the presentation of the odor-taste stimulus, impaired TPOA without affecting CTA. Contrastingly, application of muscimol before the test impaired neither TPOA nor CTA. These results suggest that ABL is involved in the acquisition but not in the retrieval of TPOA. The efficacy of muscimol microinjected after the presentation of the odor-taste stimulus further suggests that the deficit is not due to a sensory impairment but rather to the disruption of a memory process, critical for TPOA.

Amygdala↗

PubMed1997

The NMDA-receptor antagonist ketamine as an unconditioned stimulus in taste aversion learning.

Three experiments studied the effectiveness of ketamine acting as an aversive unconditioned stimulus (UCS) in a conditioned flavor aversion procedure. In Experiment 1a, three conditioning trials where sucrose was paired with ketamine produced a weak but significant aversion to sucrose; Experiment 1b showed that this effect was not due to a reduced consumption of sucrose caused by ketamine-induced neophobia. In Experiment 2, acquisition of an aversion to sucrose paired with lithium chloride (LiCl) injections was retarded by prior repeated exposure to LiCl but not to ketamine. These results are not consistent with an interpretation of previous results, showing that ketamine impairs the acquisition of flavor aversions based on LiCl-induced illness, as an example of the UCS preexposure effect.

Animals↗

PubMed2001

CAMKII inhibition in the parabrachial nuclei elicits conditioned taste aversion in rats.

The conditioned taste aversion (CTA) paradigm was used to assess the role of Ca(2+)/calmodulin-dependent protein kinase (CAMKII) in associative learning. KN62, a specific inhibitor of CAMKII, was injected into the parabrachial nuclei (PBN) either immediately after saccharin drinking (CS) or after saccharin drinking and i.p. injection of LiCl (US). Injection of KN62 into the PBN after saccharin drinking elicited clear CTA (Exp. 1). This effect was dosage-dependent and site-specific (Exp. 2). The results are discussed in relation with an earlier report showing that CTA acquisition is disrupted by injection of Ca(2+)/phospholipid-dependent protein kinase (PKC) inhibitor chelerythrine into the PBN during CS-US interval. It is suggested that the principal serine/threonine kinases play different roles in CTA learning: whereas PKC activity is necessary for the gustatory short-term memory formation, CAMKII acts similarly to the US itself-an unexpected role of CAMKII in associative learning.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗