Self-administration of ethanol and saccharin in newborn rats: effects on suckling plasticity

Responsiveness to a surrogate nipple providing water, saccharin, 5% ethanol, or 10% ethanol was tested in newborn rats naive to suckling (3-5 hr old) on Postnatal Day (P) 0 and in older neonates with regular suckling experience on P1 or P2. At all ages, pups demonstrated greater nipple attachment for saccharin or 5% ethanol than for water. Intake of saccharin and 5% ethanol was high in newborns, far exceeding that of water. At P1 and P2, pups exhibited a preference for saccharin, but not for 5% ethanol. Preexposure to a nipple providing ethanol or saccharin (but not a nipple alone or fluids alone) increased subsequent responsiveness toward an empty surrogate nipple (no fluid), both 1 hr and 24 hr after preexposure. Although, during preexposure, pups responded most positively to the nipple providing saccharin, the longest time spent on an empty nipple was observed in pups preexposed to 10% ethanol.     

The inhibitory effect of preexposed olfactory cues on intermale aggression in mice

To explore the effect of preexposure of olfactory cues on aggressive behavior, adult male mice, isolated for 14 days prior to the experiment, were preexposed for 10 days to one of 3 odors: (1) that of the opponent encountered in the test trial; (2) that of a strange mouse not subsequently encountered; and, (3) that of a neutral substance. The results show the greatest amount of aggression, as measured by latency to attack, accumulated attacking time, number of attacks and intensity of fighting, in the neutral preexposure group; an intermediate amount of aggression in the group preexposed to the irrelevant mouse odor; and the least amount of aggression in the group preexposed to the odor of the future-opponent mouse. Furthermore, preexposed animals in the third condition did not respond to attack by assuming the characteristic submissive posture. Results are discussed in terms of learned habituation to the pheromone which purportedly elicits aggression in the mouse.     

Stimulus preexposure reduces generalization of conditioned taste aversions between alcohol and non-alcohol flavors in infant rats

Results of 3 experiments showed that infant rats (age 13-17 days) generalize conditioned taste aversions between alcohol and non-alcohol tastes such as a mixture of sucrose and quinine, apple cider vinegar, or coffee. Nonreinforced preexposure to those tastes reduced generalized aversions between them. Generalization between alcohol and sucrose-quinine was reduced not only after preexposure to both tastes, but also when only the nonconditioned taste was preexposed, whereas with alcohol and vinegar, both tastes had to be preexposed to obtain that effect. In no case was generalization reduced when only the to-be-conditioned taste was preexposed. Previous experience with alcohol alone, as well as with similar gustatory stimuli, may enhance subjects' ability to differentiate them during infantile stages in rats.     

Latent inhibition in the developing rat: an examination of context-specific effects

Latent inhibition (LI) refers to the reduction in conditioned responding when the conditioned stimulus (CS) is preexposed prior to CS-unconditioned stimulus pairings. Experiment 1a demonstrated that preexposure to an odor CS prior to odor-shock pairings markedly reduced conditioned freezing in 25-day-old rats; however, this LI effect was observed only if odor preexposure and odor-shock pairings occurred in the same context (i.e., LI was context-specific at this age). The results of Experiment 1b showed that 18-day-olds also exhibited LI, but this effect was not context-specific at this age. In Experiment 2, rats were preexposed to the odor at 18 days of age and given odor-shock pairings at 25 days of age. These rats exhibited context-specific latent inhibition, suggesting that 18-day-old rats encoded the preexposure context. In Experiment 3, all parameters were identical to Experiment 2, with the exception that odor-shock pairings were given at approximately PN18 and testing occurred at approximately PN25. These rats exhibited latent inhibition at test, but this effect was not context-specific. The results of this study suggest that (a) PN18 rats can exhibit latent inhibition, and (b) the expression of context-specific latent inhibition depends on the age at which conditioning occurs.     

Relationship between preexposure to prey and PCPA-induced filicidal activity in Sprague-Dawley rats

Experiments, involving para-chloro-D,L-phenylalanine-induced pup-killing (filicide), were conducted to determine the effect of preexposure to the goal entity on the initial development and long-term expression of PCPA-induced filicide. Three groups of Sprague-Dawley rats (n = 50) were either preexposed/not preexposed, or preexposed for varying periods (5, 8, or 13 days) prior to receiving PCPA. Two major results were obtained: 1) preexposed animals were less filicidal than those not preexposed; and 2) there was an inverse relationship between the number of preexposures and filicide occurrence. The results are interpreted in reference to a serotonin-depletion habituation hypothesis.     

Maternal behavior in the undernourished rat (Rattus norvegicus)

Undernutrition was produced in rat pups and their mothers by allowing the mothers access to only 40 percent of the food that they normally would eat. Undernourished or well nourished rat pups were fostered on undernourished or well nourished mothers when the pups were 8 days old. Retrieving times and maternal behaviors were recorded for a period of 2 hr. Neither the well nourished nor undernourished mothers treated the undernourished pups significantly differently from the well nourished pups. The undernourished mothers spent more time than well nourished mothers in exploratory behaviors (rearing up and sniffing) and took longer to retrieve their pups. No significant differences occurred in the time spent with the pups or other maternal behaviors. Decreases in maternal attentiveness to pups found in previous studies may be a result of competition from exploratory or food seeking behaviors.     

Postconditioning recovery from the latent inhibition effect in conditioned taste aversion

Two experiments were conducted examining the effects of flavor (CS) preexposure on the retention of conditioned taste aversion. In Experiment 1, rats received preexposure to sucrose solution followed by a sucrose-illness pairing. The expected “latent inhibition” effect was obtained when testing occurred after a two-day but not an eleven-day training-to-test interval. Experiment 2 extended these results by employing five- and twenty-one-day training-to-test interval parameters and provided evidence that the stronger taste aversion displayed by preexposed subjects following long retention intervals is not attributable to differences in training consumption of sucrose solution. This posttraining increase in conditioned taste aversion (CTA) suggests that preexposure blocks expression of memory.     

Taste aversion following backward conditioning procedures in preweanling and adult rats

Laboratory rats, 18 and 90 days old, received an intraperitoneal injection (2% body weight) of .15M lithium chloride or .9% saline 10 or 30 min before 15-min access to 12% sucrose. Additional control groups received LiCl injection followed by tap water access. Testing with a 2-bottle choice procedure revealed reliable aversion effects for both age groups at each toxicosis-flavor interval. Adult rats showed reliably greater persistence of aversion following training with the 10- than with the 30-min interval. Rat pups showed no reliable differences in aversion across training intervals. Reliably greater aversion effects occurred for adults than for pups following training at the 10-min interval. Following training at the 30-min interval a similar reliable age effect occurred on Test Trial 1; but from Trial 2 onward the magnitude of aversion was similar for pups and adult rats.     

Signaling the unconditioned stimulus during the preexposure phase does not attenuate the unconditioned stimulus preexposure effect in preweanling rats

The unconditioned stimulus preexposure effect (US‐PE) is defined as an attenuation of the conditioned response after preexposure to the US prior to conditioning. Evidence exists that this effect can be weakened or eliminated by the presence of a signal predicting the US during the preexposure phase. This evidence has been found consistently across a variety of procedures in adult rats. The aim of the present study was to evaluate whether, in infant rats, signaling the US (LiCl) during preexposure with a salient cue (almond odor) attenuates the US‐PE. During the preexposure phase, preweanling rats received three (Experiment 1) or one (Experiment 2) preexposures to LiCl, preceded by exposure to almond odor. Appropriate control groups were also included in these experiments. After preexposure, two conditioning trials were carried out in which subjects were given LiCl after saccharin consumption. During preexposure, three (Experiment 1a), although not one (Experiment 2a), contingent exposures to almond odor and LiCl resulted in a strong odor aversion. Extinction of the learned taste aversion was facilitated by prior experience with LiCl (Experiments 1b and 2b). This effect was observed regardless of whether or not LiCl was signaled by the almond odor. These results do not coincide with the associative hypotheses proposed to explain the US‐PE, nor are they concurrent with alternative explanations based on the learned helplessness phenomenon. © 2011 Wiley Periodicals,Inc. Dev Psychobiol 54: 808–817, 2012     

Spatial exploration is required for the formation of contextual fear memory

The acquisition of contextual fear in mice is thought to require the formation of a conjunctive representation of the conditioning chamber. This can be achieved during a minimum of 20 to 40 s of exploration immediately prior to the shock or during preexposure to the context at an earlier time. An animal receiving less time in the chamber will show reduced freezing 24 hr later, a condition termed the immediate shock deficit (ISD). In this study, the authors have attempted to uncouple the formation of a contextual representation, based on the conjunction of a defined set of cues, from the establishment of a spatial representation, which requires active exploration, by inserting a transparent plastic partition in the center of the chamber. Taking advantage of the ISD and the context preexposure effect, the authors found that animals preexposed to one side of the chamber on Day 1, but shocked on the other side on Day 2, show significantly less fear than animals exposed to and shocked on the same side. Our results indicate that spatial exploration is necessary for mice to benefit from contextual preexposure.     

Familiarization and cross-familiarization of wheel running and LiCl in conditioned taste aversion

Familiarization with an unconditioned stimulus (US) interferes with the learning of subsequent Pavlovian conditioned associations. We conducted a series of experiments exploiting this US preexposure effect to elucidate the underlying mechanism of conditioned taste aversion in rats induced by voluntary wheel running. Experiment 1 demonstrated that running-induced taste aversion was alleviated if rats had sufficient experience of running in advance. In Experiments 2A and 2B, preexposure to wheel running had no effect on subsequent taste aversion conditioning by lithium chloride (LiCl) injection. In Experiment 3, however, we observed a weak partial interference from the LiCl injection pretreatment to the subsequent conditioning by wheel running US. This US crossover effect suggests the possibility that wheel running and LiCl injection share a common or similar physiological mechanism in inducing taste aversion.     

Cholecystokinin octapeptide and lithium produce different effects on feeding and taste aversion learning

The strengths of taste aversion induced by sulphated cholecystokinin 26-33 (CCK-8; 1,2,4 and 8 micrograms/kg IP) and lithium chloride (LiCl; 7.5, 15, 30 and 60 mg/kg IP) were determined in order to assess the relative aversiveness of the two compounds. All doses of LiCl induced strong aversion, but only the highest dose of CCK-8 induced aversion, which was mild. Effects of CCK-8 and LiCl on food intake were then compared in the hour (hr) following 8 hr of food deprivation; rats were on this food deprivation schedule for a relatively long time (78 days) throughout testing. All doses of CCK-8 reduced food intake significantly. Most doses of LiCl either did not affect or significantly increased food intake. Although 60 mg/kg LiCl did not affect food intake when administered 15 or 30 min before food presentation, it significantly increased food intake when administered 1, 2 or 3 hr before food presentation. Overeating of solid food may be an illness-induced behavior. Although a very high dose of LiCl (120 mg/kg) decreased food intake markedly, the rats were obviously distressed, not satiated. Failure of CCK-8 to affect feeding behavior like LiCl is indirect evidence that the reduction of food intake by CCK-8 is not merely the result of aversiveness, but is an extremely potent and specific behavioral effect.     

Lesions of basolateral and central amygdala differentiate conditioned cue preference learning with and without unreinforced preexposure

In the separated arms conditioned cue preference (CCP) task rats are trained by confining them in one arm of an eight-arm radial maze with food and in another arm on the opposite side of the maze with no food on alternate days. After two such trials, rats prefer the food-paired arm when allowed to move freely between the two arms, neither of which contains food. However, if the rats are preexposed to the maze by exploring it without food before training, no preference is observed and at least 4 training trials are required to produce a CCP, suggesting that unreinforced preexposure to the maze latently inhibits acquisition. If this interpretation is correct, preexposure should reduce the size of the preference acquired with both 2 and 4 training trials. In Experiment 1, this prediction was replicated for 2 training trials; however, with 4 training trials, eliminating preexposure also eliminated the CCP. A previous finding that basolateral amygdala lesions impair the CCP with preexposure and 4 training trials was replicated in Experiment 2, but similar lesions had no effect on the CCP in non-preexposed rats given 2 training trials. In contrast, lesions of the central nucleus impaired the 2 training trial CCP but had no effect on the 4 training trial CCP. This double dissociation suggests that the BLA-mediated 4 training trial CCP may be due to learning about the reward features of the maze space, while the central-nucleus-mediated 2 training trial CCP may be due to a conditioned approach response.     

The effects of preexposure to the drug on state dependent retention.

The present experiment examined whether previous experience with a drug would decrease the potential of the drug to produce state dependent retention (SDR) for a passive avoidance response in rats. In the first experiment, a single injection of sodium pentobarbital (20 mg/kg) given on six consecutive days before the training day slightly reduced, but did not block, pentobarbital-induced SDR. In Experiment Two, four preexposure injections of 5 IU/kg insulin reduced the magnitude of memory loss produced by administration of the hormone prior to training. As with pentobarbital, however, preexposure to insulin did not completely block the amnestic effect of the hormone. A subsequent experiment demonstrated that the decrease in the strength of insulin-induced SDR in insulin preexposed rats was not the result of enhanced acquisition. Collectively, these data indicate that noncontingent preexposure to an amnestic treatment may decrease the magnitude of memory loss that would normally result from the administration of that treatment during training.     

Enhancement of IgE antibody production by ovalbumin aerosol in mice

The effect of aerosolized ovalbumin (OA) on the induction of IgE antibody production was investigated in BALB/c mice. Enhancement of anti-OA IgE antibody production was obtained after the administration of 10 micrograms OA in mice preexposed to 1% aerosolized OA for 6 or 30 min, and after the administration of 1 microgram OA in mice preexposed to aerosolized OA for 30 min. IgE antibody production could also be induced by preexposure to aerosolized OA at a concentration as low as 0.1%. A carrier effect was observed by preexposure to aerosolized OA using a hapten-carrier system. In the latter system, whole body irradiation (200 R) could not enhance IgE response, suggesting that irradiation-sensitive suppressor T cells might be generated in insufficient amount or not at all by aerosolized OA. Preexposure to aerosolized dinitrophenol-OA could not enhance anti-dinitrophenol IgE response. These results suggest that the exposure to aerosolized antigen primed preferentially T helper cells.     

Transition from pup killing to parental behavior in male and virgin female albino rats

In the first part of this study, the effect of habituation to pups was examined in virgin female and male Sprague-Dawley rats that committed infanticide in a screening test. With repeated exposure to test pups (5-10 days old), the rats ceased to commit infanticide and came to behave parentally. Preexposure to inaccessible pups (confined inside wire-mesh baskets) did not accelerate the rate of disappearance of infanticide during subsequent contact with young, which suggests that pup killing is not a neophobic response to the novelty of young. In the second part of the study, three groups of infanticidal male Wistar rats were mated and tested for their responses towards unrelated pups after different intervals of cohabitation with their mates. The males continued to commit infanticide at the time that their mates were at midpregnancy or 24 hr before parturition, but males that cohabited with their mates till day 9 postpartum no longer attacked the young. Thus, the mother rat, presumably by means of postpartum aggression, renders her mate noninfanticidal, thereby reducing the likelihood of her offspring being harmed when she is away from the nest.     

Age-related differences in avoidance behavior in rats following CS preexposure

Weanling and adult rats were exposed to either 0 or 10 conditioned stimulus (CS) presentations prior to 1-way active-avoidance (AA) training. Although CS exposure retarded avoidance acquisition in the adults, it produced no effect in the pups during avoidance learning. Neither adult nor young rats demonstrated preexposure effects in extinction. A general extinction analysis showed that pups had less resistance to extinction than the adults, despite a comparable avoidance learning criterion between age groups. The lack of preexposure influences on performance by the pups was compared to previous findings of response inhibitory deficits in immature rats. The results were considered in light of selective attention interpretations of latent inhibition.     

NMDA receptor modulation of incidental learning in Pavlovian context conditioning

Rats exposed to a footshock show conditional fear when reexposed to the shock context. Immediate presentation of shock after placement in the context significantly reduces this fear. Preexposure to the context in the absence of shock, coupled with a minimum preshock interval during training, overcomes this immediate shock deficit. Because rats learn about the context during preexposure and express that learning after being reinforced, the context preexposure effect is an aversive analogue of latent learning. The authors examined the effect of the N-methyl-D-aspartate (NMDA) receptor antagonist D,L-2-amino-5-phosphovalerate (APV) on the facilitatory effect of context preexposure. Rats were preexposed to a chamber after APV administration. The next day they were placed in the same chamber without drug and received shock 35 s later. APV blocked the facilitatory effect of preexposure. Therefore NMDA receptors are important for contextual latent learning.     

Disruption of contextual freezing, but not contextual blocking of fear-potentiated startle, after lesions of the dorsal hippocampus

The role of the dorsal hippocampus in contextual fear conditioning was investigated with a contextual blocking paradigm. In Experiment 1, rats were given pairings of a light conditioned stimulus (CS) and footshock after preexposure either to footshock or to the context alone. The group preexposed to footshock showed poorer fear conditioning to the light CS, as measured by the fear-potentiated startle reflex. In Experiment 2, a group preexposed to footshock in the same context showed poorer fear conditioning to the light CS than did a group preexposed to footshock in a different context, indicating contextual blocking of fear-potentiated startle. In Experiment 3, lesions of the dorsal hippocampus had no effect on contextual blocking, even though contextual freezing was disrupted. The sparing of contextual blocking indicated that contextual memory was intact following hippocampal lesions, despite the disruption of contextual freezing.     

Cocaine and ethanol interaction in the conditioned taste aversion paradigm.

The aim of this study was to examine the relationship between cocaine and ethanol in a variant of the conditioned taste aversion (CTA) paradigm. The preexposure CTA procedure formed the basis of the following set of experiments. Experiments 1a and 1b assessed whether cocaine and ethanol were functionally related with overlapping stimulus properties as reflected in the preexposure CTA procedure. Male Wistar rats with restricted water access were preexposed to cocaine or ethanol for 3 consecutive days. Twenty-four hours after the last preexposure session, rats were conditioned to either ethanol or cocaine, respectively. The results of this set of experiments revealed a symmetrical interaction between cocaine and ethanol, where cocaine and ethanol effectively blocked CTA to one another. These findings suggested that there may be overlapping stimulus properties between cocaine and ethanol, which may be detected in this procedure.