Fear Retention Research Articles

Active and passive avoidance performances following bilateral olfactory bulbectomy.

Three experiments were performed to study the effects of bilateral olfactory bulbectomy upon active and passive avoidance conditioning. In the first experiment, olfactory bulbectomized rats were found not to be impaired on a one‐way active avoidance task but showed a fear retention deficit. In Experiment 2, sham‐operated rats demonstrated a degree of fear retention that was a positive linear function of the number of shock presentations; olfactory bulbectomized rats showed a total absence of fear retention. In the third experiment olfactory bulbectomized rats failed to demonstrate the inverse relationship between shock intensity and two‐way avoidance performance normally evidenced. The pattern of data obtained suggests that while bulbectomized rats do not show any general avoidance impairment they do seem to be unaffected by the suppressive effects of shock upon ongoing behavior.

Role of olfactory bulbectomy and DSP4 treatment in avoidance learning in the rat.

Olfactory bulbectomized rats and DSP4-treated rats were studied on a two-way active avoidance task as well as on step-down passive avoidance and fear conditioning and retention tasks in three experiments. The DSP4-treated, but not olfactory bulbectomized, rats were impaired in acquiring two-way avoidance; bulbectomized, but not DSP4-treated, rats were found to show notable passive avoidance and fear retention deficits. Bulbectomized rats treated with DSP4 did not show passive avoidance and fear retention deficits, nor did these animals evidence the two-way avoidance impairment of the DSP4-treated rats. No alteration of dopamine-beta-hydroxylase activity in the frontal cortex and hippocampus as a result of the bulbectomy operation was indicated. The double dissociation between bulbectomized and DSP4-treated rats is discussed in terms of opponent behavioral processes, influenced by olfactory bulbectomy and DSP4, which may permit insights into experimental investigations of stress, anxiety, and depression.

Serotonin neurons and aversive conditioning in the rat.

The acute and long‐term effects of p‐chloroamphetamine (PCA) on one‐way and two‐way active avoidance (AA), passive avoidance (PA) learning, fear retention (FR) and on central monoamine concentrations were examined in the male rat. Acute PCA administration (0.63–5 mg/kg i.p.), which releases presynaptic 5‐HT, produced a dose‐related impairment of both one‐and two‐way AA acquisition, AA retention, PA and fear retention. The selective serotonin (5‐HT) uptake inhibitor zimelidine, but not the noradrenaline (NA) uptake inhibitor desipramine, blocked the avoidance deficit induced by acute PCA. Degeneration of brain 5‐HT neurons by a high neurotoxic dose of PCA (2 × 10 mg/kg i.p.) failed to change AA and PA learning but blocked the avoidance deficit induced by acute PCA. Degeneration of locus coeruleus NA neurones with DSP4 (1 × 50 mg/kg), a selective NA neurotoxin, failed to block the acute PCA action. Thus, the acute avoidance learning impairment appears to be specifically related to the acute release of endogenous 5‐HT. Both acute and long‐term PCA treatment affected 5‐HT neurones preferentially in the forebrain while marginal effects were observed in the midbrain and spinal cord. A marked impairment in the retention and retrieval of fear conditioning in the rat was also observed following acute PCA administration. The serotoninergic mechanisms underlying the retrieval deficit were found to be similar but not identical to those involved in AA acquisition. These results suggest an important role for central 5‐HT neurones in aversive learning processes. The possible involvement of 5‐HT neurones in learning, memorial and/or retrieval processes is discussed.

Serotonin involvement in aversive conditioning: Reversal of the fear retention deficit by long-term p-chloroamphetamine but not p-chlorophenylalanine

5-Methoxy-N,N-dimethyltryptamine (5-Meo-DMT), a serotonin (5-HT) agonist, fenfluramine and p-chloroamphetamine (PCA), which are 5-HT releasers, produce deficits in fear retention as indicated by a notable lack of the immobility resulting from inescapable shocks. Depletion of central 5-HT neurones after long-term PCA treatment (2 × 10 mg/kg) completely blocked the retention impairment resulting from acute PCA (2.5 mg/kg) and fenfluramine (5 mg/kg), and partially blocked the deficit produced by 5-MeO-DMT (4 mg/kg). 5-HT depletion after p-chlorophenylalanine (PCPA) treatment (200, 100, 100 mg/kg, 72, 48 and 24 h before) did not do so; this is in agreement with other findings which suggest the involvement of different 5-HT stores in the action of PCA and PCPA. These data further underline the importance of the ascending 5-HT pathway in aversive conditioning in the rat.

Serotonin and fear retention in the rat.

p-Chloroamphetamine (PCA), which releases serotonin (5-HT) stores in brain regions, injected (5 mg/kg, ip) into male rats 40 min prior to the presentation of four inescapable shocks (.065 W) in the right-hand compartment of a normal shuttle box resulted in a profound fear-retention deficit as characterized by the total loss of the freezing and immobility posture that is normally the aftermath of shock presentation; zimelidine (10 mg/kg) 60 min before PCA completely blocked the disruption of fear. The "PCA effect" on fear retention was found at the 2.5 mg/kg but not quite at the 1.25 mg/kg dose, and when PCA (5 mg/kg) had been injected at least 8 hr before conditioning. The selective 5-HT uptake inhibitors zimelidine and fluoxetine, but not the noradrenaline (NA) uptake inhibitor desipramine, blocked the PCA effect, as did the 5-HT antagonist methergoline, but not the selective dopamine antagonist pimozide. A total retention impairment with a conditioning-testing delay of just 60 min was also evidenced, and the administration of PCA up to 2 hr before fear-retention testing also produced the retention deficit; these findings suggest some "retrieval failure." The 5-HT specificity of the PCA effect on fear retention was established by the demonstration that 5-HT-depleted rats (PCA, 2 X 10 mg/kg), but not NA-depleted rats, showed a nearly complete blockade of the fear-retention deficit. These experiments describe a role for 5-HT in both memory storage and retrieval processes.

DSP4 (N-2-chloroethyl-N-ethyl-2-bromobenzylamine), a new noradrenaline neurotoxin, and stimulus conditions affecting acquisition of two-way active avoidance.

Several stimulus (conditioned stimulus [CS] and unconditioned stimulus) variables known to affect the rate of acquisition of the two-way active avoidance task were investigated in rats treated with the novel selective noradrenaline neurotoxin DSP4 (50 mg/kg, ip). Although the DSP4 rats did not demonstrate the linear relation between CS duration and avoidance acquisition to the same extent as the control rats, their avoidance performance was as drastically disrupted as that of the controls both by preexposure to the CS and by increasing levels of shock intensity. The DSP4 rats also evidenced fear retention for the shuttle box cues previously associated with inescapable shocks to as marked a degree as control rats. Biochemical data indicated profound noradrenaline depletion in the cortex and hippocampus and a lesser depletion in the hypothalamus. It seems unlikely that the small serotonin depletions evidenced here can account for the avoidance deficits. The present findings offer a behavioral characterization of the consistent DSP4-induced impairment of two-way active avoidance acquisition.

Ovarian hormones and retention of learned fear in rats

The present series of investigations was designed to evaluate whether naturally occurring or exogenously induced hormonal changes might influence memory in a state-dependent paradigm. Rats in four experiments received Pavlovian fear conditioning to static environmental cues, followed by passive avoidance testing. In Experiment 1 animals were trained and tested in either the same stages of the estrous cycle (E-E, P-P) or in different stages (E-D, D-E, P-D, D-P). In Experiment 2 rats were trained during one stage of pregnancy, and tested for retention when hormonal conditions were presumably similar (same state) or altered (mismatched). No convincing evidence was found which would indicate that naturally occurring changes in hormonal levels associated with either stages of estrous (Exp 1) or stages of pregnancy (Exp 2) modulate retention of fear. Exogenous administrations of progesterone were employed in Experiments 3 and 4 in order to permit more direct experimental control over internal states and to enhance the salience of changes in internal environment. With a 7-day retention interval progesterone manipulations failed to influence retention performance in a state-dependent manner (Experiment 3), but with a 1-day interval asymmetrical state-dependent effects were obtained. Implications of these findings with respect to boundary conditions on the role of internal contextual cues in memory retrieval were discussed.

The acute effect of p-chloroamphetamine on the retention of fear conditioning in the rat: Evidence for a role of serotonin in memory consolidation

The acute effect of the 5-hydroxytryptamine (5-HT) releasing compound p-chloroamphetamine (PCA) on the acquisition and retention of shock-elicited fear conditioning to the contextual cues of a normal two-compartment shuttlebox in the rat was studied in three experiments. PCA (5 mg/kg) did not impair the acquisition of fear conditioning (Experiment 1). PCA, administered either 30 or 60 min before fear conditioning, caused a total blockade of fear retention when tested 24 h after acquisition. This retrograde amnesic effect was blocked by the 5-HT uptake blocker zimelidine (10 mg/kg) when PCA was injected 60 min before shock. These findings indicate that 5-HT neurones, possibly in the forebrain, may exert an inhibitory influence upon the long-term aspects of information consolidation in memory.

Age-dependent effects of preconditioning aversive experiences on the retention of conditioned fear in weanling rats

Two experiments investigated the effect of prior noncontingent shock experience upon the retention of fear in young rats. Rats given Pavlovian fear conditioning at 20 days of age and tested 2 or 4 weeks later showed less forgetting if they had received preconditioning shocks in infancy. The magnitude of this protection effect was inversely related to the age at which the prior experience had occurred. As preshock treatments did not appear to affect acquisition, the improved retention does not seem to be based upon changes in original learning. Early experience may enhance memory processes by increasing cue utilization.

Forgetting of a CS attribute in a conditioned suppression paradigm

Although a number of studies have demonstrated nearly complete retention of fear in a conditioned suppression task, they provide little information about the nature of the memory for the CS. The purpose of the present experiment was to investigate the retention of an attribute of a tonal CS that had been paired with shock and was thus capable of eliciting a conditioned emotional response (CER) in rats. The Kamin blocking effect was utilized to detect changes in the memory of CS attributes. Either 1 or 21 days following conditioning to a tone, separate groups of rats received compound conditioning in which either the original or a novel tone was combined with a light. Subsequent measurement of suppression to the added element (light) indicated that only the original CS produced blocking at the short delay, but that both original and novel tones resulted in blocking at the 21-day interval. This increase in the extent of blocking suggests that memory for specific attributes of the CS does diminish as a function of time.

Reduction of ontogenetic retention decrements in rats by pretraining stressful experiences.

Pretraining stressful experiences, either similar to or qualitatively different from the conditioning unconditioned stimulus, reduced ontogenetic retention decrements without directly influencing response acquisition. Rats that received pretreatment with footshock, hypthermia, or restraint on Days 16, 17, and 18 of age showed substantially improved long-term retention of conditioned fear learned at 20 days of age. It was also found that preshock enhanced retention of both an appetitive approach response and punishment of the approach response. Several experiments involving extinction and undertraining manipulations indicated that the facilitation of retention was not directly attributable to acquisition strength.

Fear Conditioning and Extinction in Rats at Different Times of Day

Summary Random bred male animals (N = 48 rats) underwent classical fear conditioning, an extinction trial, and a subsequent fear retention test either in the morning or in the afternoon. Half of the animals in both groups had been deprived of food for 18 hours prior to testing and were offered some food in the final fear retention test, whereas the others carried on feeding ad lib. The four groups were further split up into groups of three animals with a duration of the extinction trial of either 0, 15, 30, or 60 sec. Food deprivation had no significant effect on the fear retention data. But animals which had been tested in the afternoon showed greater fear reduction following a short duration of extinction than after a long duration. Animals tested in the morning, on the other hand, profited more from longer duration of extinction.

Forgetting of conditioned fear inhibition

Three experiments assessed retention of conditioned fear and of fear inhibition over long-term retention intervals (35 days in two experiments, 25 days in the third). Although excitatory conditioning was retained well, conditioned inhibition was not. This effect occurred when inhibition was assessed by compounding stimuli on an appetitive baseline and when it was assessed by testing cues on a baseline of unsignalled avoidance responding. Inhibition was also forgotten when the initial conditioning treatment was designed to reduce the role of possible proactive interference processes.

Effects of Cannabis sativa extract on conditioned fear

Male and female rats were chronically or acutely treated with marihuana extract before or after being subjected to a conditioned emotional response (CER) paradigm. Acute administration of the marihuana compound partially blocked both acquisition and retention of conditioned fear. After chronic administration, however, only retention of the conditioned suppression was affected.

Acute sympathectomy by 6-hydroxydopamine in the adult rat: effects on cardiovascular conditioning and fear retention.

Acute sympathectomy by 6-hydroxydopamine in the adult rat: effects on cardiovascular conditioning and fear retention.

Retrograde amnesia: production of skseletal but not cardiac response gradient by electroconvulsive shock.

Rats given a single electroconvulsive shock immediately after but not 60 seconds after an aversive conditioning trial exhibited behavioral retention deficits 24 hours later in a one-trial passive avoidance task. In contrast to these differential performance deficits, similar heart-rate changes, indicative of fear retention, were seen in punished animals irrespective of the time of delivery of the shock. These data suggest retention of a generalized fear to the training experience that was not revealed by the behavioral measure. The potential usefulness of concomitant behavioral and physiological response assessment in consolidation research is discussed.

Conditions influencing the retention of learned fear in young rats.

Conditions influencing the retention of learned fear in young rats.

Conditioned inhibition of exploration in young rats

The inhibition of exploratory behavior, and responses to the CS were used as measures of conditioned fear in young rats. Comparisons with control groups indicate that any experience with shock produces equal amounts of fear retention in the early and middle stages of extinction. The differential effects produced by the various procedures became apparent only later in extinction when the group that had experienced CS-US pairings in acquisition exhibited significantly more residual fear than the controls on both response measures.

Genetic analysis of acquisition and retention of a conditioned fear in mice.

Genetic analysis of acquisition and retention of a conditioned fear in mice.

Retention of fear

Retention of fear decreased over intervals of 22 hrs., 30, 60 and 90 days after classical fear conditioning. Fear retained at 22-hr. and 30-day intervals was sufficient to provide the basis for new instrumental learning.