PubMed Health⌕ Search

Biomedical subjects

Pamela S Hunt

Publications and source records attributed to Pamela S Hunt.

12 recordsLinked to original sources

Pharmacological dissociation of trace and long-delay fear conditioning in young rats.

In most studies comparing trace and delay conditioning, CS duration is kept constant across training conditions but the interstimulus interval (ISI), the time from CS onset to US onset, is confounded. In the infrequently used long-delay condition, however, ISI is kept constant across the trace and delay conditions but CS duration varies. A recent study reported that trace and long-delay fear conditioning have the same developmental trajectory, with both emerging later in development than standard-delay conditioning (). Past studies have shown that trace conditioning is mediated by the cholinergic system; given the parallel developmental emergence of trace and long-delay conditioning, the present study examined whether the cholinergic system also mediates long-delay conditioning. Two experiments, both involving Sprague-Dawley-derived rats and using freezing as a measure of learned fear, showed that the cholinergic system is critically involved in trace conditioning but is not involved in long-delay conditioning. Specifically, pre-training injections of the muscarinic receptor antagonist scopolamine impaired acquisition of a CS-US association in 32-day-old rats trained with a trace procedure but had no effect on rats this age trained with a long-delay procedure (Experiment 1). Similarly, pre-training injections of physostigmine, a cholinesterase inhibitor, enhanced acquisition of trace conditioning in 25-day-old rats but had no effect on long-delay conditioning in rats this age (Experiment 2). Taken together, the results indicate that despite the similarities between trace and long-delay conditioning in terms of developmental emergence and level of conditioned responding, they are mediated by different physiological systems.

Age Factors↗

Cholinergic modulation of trace conditioning trained in serial compound: A developmental analysis.

In four experiments the effects of serial compound conditioning on responding to a trace-conditioned CS were evaluated using a fear conditioning paradigm. The subjects were 18- and 25-day-old Sprague-Dawley rats, previously shown to exhibit little or no trace fear conditioning. Here, animals as young as 18 days of age were shown to be capable of trace conditioning between a visual CS1 and a shock US, provided the trace interval was filled with a non-target CS2 during serial conditioning trials (CS1-->CS2-->US). To explore cholinergic mechanisms involved in trace and serial conditioning, additional experiments assessed conditioned responding following pre-training administration of the muscarinic receptor antagonist scopolamine. Scopolamine produced a dose-dependent reduction in responding to the trace CS1, regardless of whether subjects were trained with standard trace (CS1-->trace interval-->US) or serial (CS1-->CS2-->US) trials. Responding to CS2 was unaffected by scopolamine. These data suggest that central cholinergic systems are functional in the young animals, but are not normally sufficiently activated by standard trace conditioning procedures. The results suggest that serial compound conditioning can promote trace conditioning in young rats, as it does in adults, perhaps by enhancing cholinergic activity during training. Implications for the late ontogenetic emergence of trace conditioning as it relates to maturation of neural pathways and their role in the potentiating effects of a gap filler are discussed.

Age Factors↗

Neonatal treatment with a competitive NMDA antagonist results in response-specific disruption of conditioned fear in preweanling rats.

RATIONALE: The N-methyl-D-aspartate (NMDA) receptor has been implicated in processes of neurodevelopment, including cell proliferation, synaptogenesis, and apoptosis. Several studies have reported that administration of NMDA antagonists early in development can cause long-lasting changes in behavior. For example, Gould and Cameron [Behav Neurosci 111:49-56 (1997a)] have shown that a single injection of the competitive NMDA antagonist CGP 43487 on postnatal day (PD) 5 affected behavioral immobility in young rats exposed to the odor of a natural predator. OBJECTIVES: This experiment was undertaken to determine whether the behavioral effects previously reported would also be seen with conditioned cues. Both stimulus-elicited behavioral immobility (freezing) and changes in heart rate were recorded to examine impairments in responding across multiple measures. METHODS: Animals were given a single injection of 0, 2.5, or 5.0 mg/kg CGP 43487 on PD 5. On PD 20 subjects were given paired or unpaired presentations of either an olfactory or auditory conditioned stimulus (CS) with a 110-dB-white-noise unconditioned stimulus. CS-elicited freezing and changes in heart rate were measured. RESULTS: Pups treated with CGP exhibited impairments in conditioned freezing, but were unaffected in their expression of conditioned changes in heart rate, to both olfactory and auditory stimuli. CONCLUSIONS: These results indicate that neonatal treatment with an NMDA antagonist affects the expression of fear in a response-specific manner. The data suggest that antagonist-induced alterations in neural systems involved in the expression of freezing are affected by NMDA receptor blockade early in life.

2-Amino-5-phosphonovalerate↗

Impaired trace fear conditioning following neonatal ethanol: reversal by choline.

Neonatal ethanol exposure in animals results in performance deficits on tests of hippocampus-dependent spatial memory, and recent studies have shown that extra dietary choline can ameliorate some of these impairments. In this experiment, rats were administered 5.25 g/kg ig ethanol per day or sham intubations on Postnatal Days (PD) 4-9 and choline (0.1 ml of an 18.8 mg/ml solution) or saline subcutaneously on PD 4-20. On PD 30, rats were given delay or trace fear conditioning trials and were tested for conditioned stimulus-elicited freezing 24 hr later. Neonatal ethanol produced a profound impairment in trace conditioning that was reversed by choline. Groups did not differ in delay conditioned responding, indicating that neonatal ethanol produces a relatively selective cognitive deficit that can be alleviated with supplemental choline.

Animals↗

The expression of fear-potentiated startle during development: integration of learning and response systems.

Relative to freezing, fear-potentiated startle (FPS) is developmentally delayed. Rats trained on Postnatal Day (PD) 18 expressed conditioned stimulus learning on PD 19 in freezing but not in FPS, whereas rats trained on PD 24 and tested on PD 25 expressed both freezing and FPS (Experiment 1). According to a neural maturation hypothesis, this delay results from functional immaturity of pathways mediating FPS. When rats were trained on PD 18, neither delaying the FPS test, allowing FPS pathways to develop, nor administrating the "reminder" treatment, the expression of FPS was promoted (Experiments 1, 2, and 2A). PD 18 learning was expressed in FPS on PD 25 when nontarget conditioned stimulus-unconditioned stimulus training occurred prior to the test, and this effect was modality dependent (Experiments 3 and 4). The authors conclude that engaging mechanisms of associative encoding when FPS pathways are functional is a critical condition for integrating learning and FPS response systems in development.

Acoustic Stimulation↗

Postnatal ethanol exposure disrupts signal detection in adult rats.

Human prenatal ethanol exposure that occurs during a period of increased synaptogenesis known as the "brain growth spurt" has been associated with significant impairments in attention, learning, and memory. The present experiment assessed whether administration of ethanol during the brain growth spurt in the rat, which occurs shortly after birth, disrupts attentional performance. Rats were administered 5.25 g/kg/day ethanol via intragastric intubation from postnatal days (PD) 4-9, sham-intubation, or no intubation (naïve). Beginning at PD 90, animals were trained to asymptotic performance in a two-lever attention task that required discrimination of brief visual signals from trials with no signal presentation. Finally, manipulations of background noise and inter-trial interval duration were conducted. Early postnatal ethanol administration did not differentially affect acquisition of the attention task. However, after rats were trained to asymptotic performance levels, those previously exposed to ethanol demonstrated a deficit in detection of signals but not of non-signals compared to sham-intubated and naïve rats. The signal detection deficit persisted whenever these animals were re-trained in the standard task, but further task manipulations failed to interact with ethanol pretreatment. The present data support the hypothesis that early postnatal ethanol administration disrupts aspects of attentional processing in the rat.

Animals↗

Early postnatal ethanol administration does not affect prepulse inhibition in rats.

Human prenatal ethanol exposure is associated with relatively widespread cognitive deficits but it is unclear whether general deficits in responsivity to sensory stimuli contribute to or underlie the deficits in later or more complex stages of information processing. The present experiment assessed the effects of early postnatal ethanol administration in rats on prepulse inhibition, with animals tested in adolescence (postnatal day (PD) 35) and early adulthood (PD 70). Animals were assigned to receive ethanol (5.25 g/kg) via intragastric intubation on PD 4-9, sham-intubation, or to a naive control group. Pre-exposure to ethanol did not differentially affect the magnitude of the response to the startle stimulus alone nor did it affect the percent inhibition of the startle response on trials with a prepulse stimulus. Male rats exhibited a greater percent inhibition than female rats on PD 35 at all interstimulus intervals (ISIs) except the shortest, 4 ms. Female rats exhibited a greater percent inhibition than male rats at all ISIs on PD 70. Collectively, these data demonstrate that cognitive deficits associated with early exposure to ethanol may not be attributable to deficits in sensorimotor gating, at least to the extent this construct is measured by prepulse inhibition.

Animals↗

Trace and long-delay fear conditioning in the developing rat.

In two experiments with rats, we examined the developmental emergence of conditioned freezing following trace and short-delay conditioning and also included a long-delay comparison group. In the short-delay and trace groups, a 10-sec conditioned stimulus (CS) was paired with shock; for the trace rats, a 10-sec trace interval followed CS termination. The long-delay groups received a 20-sec CS paired with shock, to equate for the longer interstimulus interval (ISI) in the trace group. Trace conditioning emerged later in development than did short-delay conditioning (see Moye & Rudy, 1987). Importantly, long-delay conditioning emerged in parallel with trace conditioning, at a similar time, and with similar strength. These findings suggest a role for the longer ISI, as opposed to the unfilled gap per se, in the late emergence of trace conditioning. The role of the hippocampus in trace conditioning and the possibility that young rats encode the temporal relationship between CSs and unconditioned stimuli are also considered.

Animals↗

Social learning about ethanol in preweanling rats: role of endogenous opioids.

The role of the endogenous opioid system in social learning about ethanol was examined in three experiments using preweanling rats. Experiment 1 showed that interactions with intoxicated siblings in the home cage on postnatal Days (PD) 12, 14, and 16 results in increased voluntary intake of ethanol when subjects are tested 24 hr after the final exposure. The results also suggested that the endogenous opioid system is not involved in acquisition. Administration of naloxone during social exposure to ethanol had no effect on later ethanol intake. Experiment 2 examined the effects of receptor-selective antagonists administered prior to test. For subjects that had social exposure to ethanol, intake of ethanol was completely suppressed by either naloxone or the delta antagonist naltrindole. For ethanol-naïve subjects, intake also was completely suppressed by naloxone. However, intake was partially blocked by naltrindole or the micro antagonist beta-FNA. Experiment 3 confirmed the differential involvement of micro and delta receptors in ethanol intake through a more comprehensive dose-response analysis of beta-FNA and naltrindole. Collectively, these data reveal that learning about ethanol from intoxicated conspecifics not only affects voluntary intake of ethanol but also alters the opioidergic response to ethanol consumption.

Animals↗

Postnatal binge ethanol exposure affects habituation of the cardiac orienting response to an olfactory stimulus in preweanling rats.

BACKGROUND: Prenatal exposure to alcohol can result in intellectual impairments, reduced habituation and distractibility, visual-spatial deficits, and problems in attention. Dysfunction in attention, including habituation of responses to nonsignal stimuli, can have devastating consequences for cognitive development. This research examined whether binge exposure to ethanol on postnatal days (PD) 4 to 9 would affect cardiac orienting or response habituation to an olfactory stimulus in preweanling rats. METHODS: Ethanol-exposed subjects were given ethanol 5.25 g/kg/day on PD4 to 9. Controls were either sham intubated or unhandled during this time. To assess baseline and phasic cardiac function, PD16 subjects were tested under differential pharmacological blockade of the sympathetic or parasympathetic nervous systems by administration of the peripherally acting antagonists atenolol or atropine methyl nitrate. In a second experiment, separate groups of subjects were tested for habituation of the cardiac orienting response to an olfactory stimulus. RESULTS: Results indicate that postnatal ethanol had no observable effect on the functional development of autonomic control over heart rate. Similarly, ethanol exposure had no effect on the form or magnitude of the cardiac orienting response. However, neonatal ethanol exposure did result in a deficit in orienting response habituation; ethanol-exposed subjects continued to respond to the stimulus with a large-magnitude bradycardia after control subjects exhibited complete response habituation. In addition, ethanol-exposed subjects had longer orienting response latencies than controls. CONCLUSIONS: The results indicate that this animal model has the potential to contribute to investigations designed to understand basic forms of memory impairments observed in humans with a history of prenatal alcohol exposure. The postnatal binge ethanol model of fetal alcohol effects produces deficits in nonassociative memory that are similar to those observed in human infants exposed prenatally to ethanol. Deficits in response habituation have important implications for cognitive development.

Animals↗

Intermittent ethanol exposure in adolescent rats: dose-dependent impairments in trace conditioning.

BACKGROUND: Recent studies have revealed that the adolescent brain may be especially vulnerable to ethanol-induced toxicity. Corticolimbic regions are more severely damaged following ethanol exposure during adolescence than during adulthood. The consequences of adolescent ethanol exposure on cognition however, have only recently begun to be explored. METHODS: Male and female rats were administered 0, 1.5, 2.5 or 4.5 g/kg ethanol (20% v/v) by acute intragastric gavage during adolescence (postnatal days [PD] 28, 30, 32 and 34). On PD 40, half of the subjects in each dose group were given 5 pairings of a 10-sec flashing light (CS; conditioned stimulus) immediately followed by mild footshock (US; unconditioned stimulus), a procedure known as delay conditioning. The other half were also given 5 CS-US pairings, but the US was presented 10 sec after CS offset, a procedure known as trace conditioning. All subjects were tested for CS-elicited freezing 24 h later. RESULTS: There was no effect of adolescent ethanol exposure on delay conditioned responding, with all subjects demonstrating comparable levels of CS-elicited freezing. In contrast, the amount of freezing in the trace conditioned subjects was negatively correlated with prior ethanol dose. Specifically, exposure to 2.5 or 4.5 g/kg during adolescence resulted in a deficit in trace conditioned responding. CONCLUSIONS: These data indicate that intermittent exposure to ethanol during adolescence results in impairment in hippocampal-dependent trace conditioning that persists beyond the period of ethanol exposure. Delay conditioning was unaffected by prior ethanol treatment, indicating that there was no difficulty in detecting the CS or US, or in the ability to engage in freezing behavior. These results suggest that the adolescent brain may be particularly vulnerable to the effects of repeated exposure to ethanol that can have consequences for nonspatial, hippocampal-dependent cognitive abilities.

Age Factors↗

Modality-specific impairments in response habituation following postnatal binge ethanol.

The rate of habituation of the heart rate orienting response (OR) to both olfactory and auditory cues was examined in subjects neonatally exposed to ethanol. Subjects were administered 5.25 g/kg/day ethanol in a binge-like manner on either postnatal days (PDs) 4-9 or 10-15. Controls were given sham intubations. Ethanol exposure had no effect on the form or magnitude of the heart rate OR; all subjects exhibited a monophasic bradycardia to the olfactory and auditory cues. However, ethanol treatment severely affected the rate of response habituation to an olfactory cue, regardless of the timing of that exposure. Ethanol treatment on either PDs 4-9 or 10-15 resulted in a failure of animals to show complete heart rate response habituation. For the auditory cue, rate of response habituation was unaffected by ethanol treatment. These results indicate that response habituation deficits in a postnatal model of human fetal-alcohol exposure are modality specific. The response habituation paradigm may be useful for studying mechanisms of short-term recognition memory deficits following early alcohol exposure, although modality of the test stimulus needs to be taken into account. The results suggest that central nervous system structures affected by ethanol may be specific to those involved in olfactory processing, such as the olfactory bulb or hippocampus.

Acoustic Stimulation↗