David C. Riccio

Forgetting of stimulus attributes : methodological implications for assessing associative phenomena

Differential responding to changes in the stimulus situation, long central to the concept of stimulus control, also provides the implicit conceptual basis for assessing the nature of a variety of associative relationships. However, there is substantial evidence that the perception of stimulus similarity is not a static property. Generalization gradients to contextual as well as discriminative stimuli flatten over time, and this increase in perceived similarity presumably reflects forgetting of the detailed characteristics or attributes of stimuli. Methodologically, the flattening of the gradient imposes an important constraint: The effect of a stimulus shift will be highly sensitive to the length of the delay interval between training and testing. Conceptually, the loss of memory for stimulus attributes also implies that the sources of interference in retention can increase over time.

Amnesia induced by hypothermia as a function of treatment-test interval and recooling in rats

In Experiment I, a repeated tests procedure was employed to assess hypothermia-induced amnesia of a footshock experience. Rats tested 4 h after training treatment showed no memory loss, but amnesia was present at 24 h. Although recovery of memory was obtained when the same animals were cooled 2 h prior to a 50-h test, repeated testing also tended to attenuate amnesia. In Experiment II, independent groups were tested at 6 or 50 h after training treatment. Again, memory of the footshock was present at the short, but not at the long, interval. Recooling shortly prior to the 50-h test eliminated amnesia. Experiment III indicated that the return of memory produced by recooling did not persist if testing was delayed. These findings suggested that hypothermia may function as an important contextual cue for memory retrieval.

Paradoxical enhancement of conditioned suppression

Summary Groups of rats were given Pavlovian pairings of tone (CS) and electric shock, followed by 15-sec, 10-min, or no exposure to the CS without shock. In a subsequent test, rats in the 15-sec exposure group showed more suppression of licking behavior in the presence of the CS than other subjects (i.e. greater CER than non-exposed controls). This “paradoxical enhancement” phenomenon suggests that unreinforced presentation of fear stimuli (CS without UCS) cannot uncritically be assumed to reduce response strength.

Overshadowing effects in the stimulus control of morphine analgesic tolerance.

This study attempted to replicate previous demonstrations of classical conditioning of morphine analgesic tolerance, with the additional aim of determining whether stimulus overshadowing effects might explain previous conflicting findings. Eight groups of rats received a series of 10 morphine (5 mg/kg) and/or saline injections, differing only with respect to the contingency between a compound visual-auditory conditioned stimulus (CS) and the substance injected. When tested for analgesic responding to morphine in the presence of the compound CS, only those groups for which the CS and morphine injections were paired during the acquisition sequence evidenced tolerance. In a second experiment, tolerant animals were tested in the presence of one component of the compound CS. When a loud (85 dB) tone was used in the compound, less analgesic tolerance was elicited later by the weaker visual stimulus alone. This differential stimulus control of the analgesic response suggests that overshadowing may contribute to failures to replicate conditioned morphine tolerance. That internal morphine-produced stimuli might overshadow external cues is considered.

Hypothermia-induced amnesia for newly acquired and old reactivated memories: Commonalities and distinctions

A series of six experiments compared the characteristics of hypothermia-induced amnesia for newly acquired and old reactivated memories. Old memory, when reactivated by cue exposure, was disrupted by mild or deep hypothermia treatment, while new memory was impaired only by deep cooling. Mild hypothermia had no disruptive influence on either new or old memories. Old, but not new, learning showed recovery from amnesia in a test-retest procedure. The onset of amnesia was more rapid for an old reactivated memory than for a newly acquired memory. The susceptibility of memory to disruption decreased over time following original learning or cue reactivation, although this decrease was, if anything, more rapid following the cuing procedure. Recovery from amnesia could be induced by a recooling reminder treatment and was similar for both new and old memories. It was suggested that activity of, or access to, memory rather than age per se determines susceptibility to disruption. The process of memory reactivation appears somewhat more sensitive, rapid, and brief than the processes) of memory formation. However, that the underlying old memory remains stable over time was supported by the strong retention when specific implicit or explicit reactivation cues were available.

Anomalous properties of hippocampal lesion-induced retrograde amnesia

Retrograde amnesia can result from transient or permanent insults to the central nervous system and is typically manifest as a temporally graded memory loss. This temporal gradient of retrograde amnesia has been considered evidence for memory consolidation, since newly acquired information is vulnerable to amnestic treatments, whereas older information is not. Although investigations of transient insult-induced retrograde amnesia have provided evidence against a consolidation interpretation, hippocampal lesion-induced retrograde amnesia is still considered to represent a consolidation (or storage) failure. In order to investigate the consolidation interpretation of hippocampal lesion-induced retrograde amnesia, two experiments were undertaken. In the first, rats were reminded of “old” memories prior to hippocampal lesions, a procedure that produced retrograde amnesia. This result is difficult to reconcile with current interpretations of retrograde amnesia, since consolidated memories are presumably not vulnerable to amnesia. The second experiment explored the permanence of hippocampal lesion-induced retrograde amnesia by presenting amnestic rats with a portion of the training treatment (reactivation) prior to testing. The reactivation treatment successfully reversed retrograde amnesia. Taken together, the results from these experiments indicate that hippocampal retrograde amnesia may not in all cases arise from storage failure and illuminate new circumstances under which damage to the hippocampus may affect memory.

Memory Reactivation Effects Independent of Reconsolidation

Memory reactivation is an important process resulting from reexposure to salient training-related information whereby a memory is brought from an inactive to an active state. Reactivation is the first stage of memory retrieval but can result from the exposure to salient cues without any behavioral output. Such cue-induced reactivation, although frequently used by neuroscientists to study reconsolidation, has seldom been considered as a process in its own right and studied as such. This review presents arguments indicating that memory reactivation has two main consequences: (1) to enhance the accessibility of the target memory and (2) to make the memory malleable. Accordingly, reactivation creates a transient state during which the content of the memory is easily accessible and can be modified and/or updated. As both of these aspects can be observed shortly after memory reactivation, this review emphasizes that reconsolidation is not necessarily required for these processes and calls attention to reactivation as a factor in the dynamics of the memory.

Amnesia induced by hyperthermia: An unusually profound, yet reversible, memory loss

The present series of investigations was designed to evaluate whether hyperthermia, produced by whole body immersion in warm (45°C) water, could serve as an amnestic agent. In Experiment 1, previously shocked and experimentally naive rats received one-trial passive avoidance training followed by hyperthermia treatment after delays of either 30 sec, 5, 30, or 60 min. Each of three dependent measures indicated the retention of the experimentally naive rats was susceptible to disruption through treatment delay intervals of 1 hr. In the previously shocked animals, retention was impaired only at the 30-sec interval. No evidence for spontaneous recovery was observed 48 hr after training. Experiment 2 investigated whether hyperthermia or hypothermia would impair memory over multiple training/amnesic treatment/test sequences. On the initial test trial both groups were amnestic. However, over four test sequences each separated by 24 hr the amnestic effects of body cooling, but not of warming, diminished significantly. Anterograde effects of hyperthermia did not appear responsible for the repeated memory loss as good retention was observed 24 hr after a fifth training trial. In Experiment 3, noncontingent footshock produced substantial memory recovery from both hyperthermia- and hypothermia-induced amnesia relative to sham-trained controls which also received the reminder treatment. Despite the unusual potency of hyperthermia as an amnestic agent, the attenuation of the amnesia by reminder treatment suggested an interpretation consistent with a general retrieval-oriented theory.

Hypothermia-induced retrograde amnesia: Role of body temperature in memory retrieval

The relationship of body temperature to the onset, and the subsequent alleviation, of hypothermia-induced retrograde amnesia (RA) was investigated. In Experiment 1, the retention of a passive avoidance task and the body temperature at the time of testing were assessed at intervals of 4, 8, 12, and 16 h after training/amnesic treatment. While retention was evident for up to 12 h posthypothermia treatment, it was clear that body temperature did not index magnitude of RA. A second experiment examined the alleviation of hypothermia-induced RA as a function of body temperature and retention interval. Memory recovery was facilitated at both 1- and 7-day intervals when testing occurred at 29°-31°C but not at 33°–35°C. The possibility of different mechanisms underlying retention after hypothermia and retrieval after recooling was suggested. An alternative explanation in terms of contextual cues and cue utilization was also discussed.

Alcohol self-administration in rats: Modulation by temporal parameters related to repeated mild social defeat stress

Clinical evidence often points to stress as a cause or an antecedent to the development of drinking problems. Yet, animal models of alcohol drinking have yielded inconsistent evidence for a direct contribution of stress, and many studies have shown that stress suppresses alcohol consumption. The aim of the present study was to examine alcohol reward in animals exposed to repeated, mild social stress, and to determine whether alcohol drinking changes as a function of the temporal parameters of alcohol access relative to the stressor. Male Long-Evans rats, trained to self-administer a 6% (wt/vol) alcohol solution using a sucrose-fading procedure, were exposed to five brief (5min) episodes of contact with an aggressive male. Full contact with the resident was limited to a single episode of defeat, whereas the following four encounters occurred with the subjects behind a protective wire mesh cage. Alcohol self-administration was measured 1 week prior to stress (baseline), on each day of stress exposure, and 1 week following stress. Separate groups of animals were randomly assigned to self-administer alcohol immediately prior, immediately following, or 2h following defeat stress. Stress preferentially increased alcohol drinking on stress-exposure days, and further elevated the amount consumed 1 week following stress. Temporal parameters of alcohol access relative to the stressor were found to be important. Average alcohol consumption was greatest for animals drinking 2h postdefeat, whereas animals drinking immediately prior to or following the stressor did not show a significant increase in alcohol consumption. Results suggest that mild social defeat stress is sufficient to elicit increases in alcohol consumption in nonpreferring strains of rodents, provided alcohol access occurs at an optimal time interval after the social defeat experience.