Glenn C. Abrahamsen

Environmental enrichment : the influences of restricted daily exposure and subsequent exposure to uncontrollable stress

Environmental enrichment has been proposed to enhance an animals subsequent ability to learn. While this proposal has received considerable support from experiments involving maze tasks, it has received equivocal support from experiments employing operant and pavlovian tasks. The purpose of the present study is two-fold. The first is to demonstrate that a regimen of restricted daily exposure to environmental enrichment is capable of producing effects similar to those using more standard exposure regimens when compared to the most appropriate control, a group given social exposure. The second is to examine the proposed learning enhancement of environmental enrichment on an operant task both before and following exposure to uncontrollable stress. Uncontrollable stress, as interpreted by learned-helplessness theory, results in the formation of an expectancy of response-reinforcer independence which proactively interferes with the subsequent acquisition of response-outcome associations. It may be possible, then, that environmental enrichment and uncontrollable stress may interact in such a way as to allow the potential learning effects of environmental enrichment to be assessed on an operant task. Rats were exposed to differential environments; one group exposed to an enriched environment and another exposed to a social environment 2 hours daily for 30 days. Each group was then tested on the object-exploration test. Following the acquisition of an appetitive-operant response, a subset of these two groups was exposed to either controllable, uncontrollable, or no stress using parameters known to induce learned helplessness. Animals were then tested on an appetitive-noncontingent test. It was found that, while the enrichment procedure was effective in producing effects on the object-exploration test, environmental enrichment did not modify the acquisition of the operant or the effect produced by uncontrollable stress on the appetitive-noncontingent test.

Sex differences in relation to conditioned fear-induced enhancement of morphine analgesia

A number of studies have reported that both the immediate and proactive effects of exposure to a shock stressor are less pronounced in female than in male rats. A separate area of research has demonstrated that female rats are less sensitive to the analgesic effects of morphine than males. Experiments from our laboratory, as well as others, have found that exposure to a context associated with shock (i.e., conditioned fear context) at the time of morphine administration, enhances the analgesic effects of morphine. Since previous studies have exclusively employed male rats, the purpose of Experiment 1 was to determine if a sex difference exists to this context conditioned fear-induced enhancement of morphine-induced analgesia. The findings of Experiment 1 showed that females do not appear to exhibit conditioned fear-induced enhancement of morphine analgesia as compared to males. Experiment 2 demonstrated that females exhibited higher levels of conditioned fear-induced enhancement of morphine analgesia during diestrus I than estrous. Experiment 3 demonstrated that females exhibited lower levels of conditioned analgesia compared to males, while both groups exhibited similar freezing levels. The findings of the present experiments suggest that the sex difference observed in Experiment 1 may be due to differences in conditioned analgesia.

Modulation of hypoalgesia by morphine and number of shock trials: Covariation of a measure of context fear and hypoalgesia

In a recent series of studies, we observed that exposure to prolonged foot shock increased hypoalgesia induced by morphine. This increase was observed only when testing was conducted in the presence of shock-associated cues, suggesting that it resulted from context-conditioned fear. However, we do not know whether the extended stressor parameters employed in that study are necessary for an observance of the effect. Therefore, in the present study, we assessed the effect of the number of shock trials (either 0, 20, 100, or 200) on the hypoalgesia observed following morphine administration. In addition, we measured activity as an independent index of context-conditioned fear, because in prior studies there had been no independent behavioral assessment of the conditioning of fear to the context. Although others have shown a covariation of conditioned fear and context-induced hypoalgesia using shock parameters and test paradigms different from our own, we sought to assess whether the same covariation would hold for conditioned fear and the hypoalgesia observed following the administration of morphine. The results showed increased hypoalgesia in all groups exposed to foot shock, demonstrating that prolonged exposure to foot shock is not necessary for an observance of this effect. In addition, the results revealed a linear relationship between number of trials of shock and hypoalgesia, but a U-shaped relationship between trials and activity. The pattern of results is considered in light of Fanselows Perceptual-Defensive-Recuperative model.

Pavlovian aversive context conditioning using carbon dioxide as the unconditional stimulus.

Four experiments were conducted to examine the utility of carbon dioxide (CO2) as an aversive unconditioned stimulus (US) in a Pavlovian context conditioning paradigm. Experiment 1 demonstrated that rats exposed to CO2 in a distinctive context showed elevated levels of freezing relative to controls. Experiment 2 replicated this basic effect with a modified conditioning procedure and additionally demonstrated conditioned analgesia. Experiment 3 demonstrated a positive monotonic relationship between US duration and resistance to extinction of freezing behavior as well as conditioned analgesia. Experiment 4 demonstrated extinction and an extinction-related phenomenon, renewal. These studies clearly demonstrate the utility of CO2 as a Pavlovian US.

Learned helplessness inducing foot shock can exacerbate morphine responsiveness

Exposure to inescapable tail shock or foot shock has been shown to produce effects on a number of learning tasks. Tail-shock exposure is also known to influence nociception and morphine reactivity. The present series of experiments investigated the effects of foot shock known to induce learned helplessness effects in our laboratory on the subsequent reactivity to morphine. A first set of experiments investigated the hypoalgesic response to a 4 mg/kg dose morphine over 4 consecutive days following exposure to foot shock. Experiment 1A did not reveal an effect of foot shock on morphine-induced hypoalgesia when testing was conducted in a novel context. In Experiment 1B, we observed an increased hypoalgesic response to morphine when testing was conducted in the shock context. The findings of Experiment 1B were replicated in Experiment 2 and extended to assess the contribution of conditioned fear hypoalgesia to these effects. The possible mechanisms responsible for these findings are discussed.

Conditioned fear exacerbates acute morphine dependence

A variety of physical stressors have been shown to enhance reactivity to opioid drugs. Few studies have examined the effects of nonphysical stressors on opioid drug reactivity. In this regard, it has previously been shown that animals administered morphine in the presence of shock-associated cues demonstrate increases in hypoalgesia relative to nonshock control animals. These findings have typically been viewed as being mediated by the activation of endogenous pain inhibition systems via conditioned fear. In this series, we further examined the nature of these effects by assessing the effects of conditioned fear on acute morphine dependence. Experiment 1 revealed that animals administered 3 mg/kg morphine in the presence of context fear cues demonstrated an enhanced withdrawal response when removed and administered 3 mg/kg naloxone. Because it is known that conditioning effects do not diminish over time, a second experiment examined whether the enhancement of acute dependence by context fear would still be evident 72 h postconditioning. As in Experiment 1, animals administered morphine in a context associated with shock demonstrated an enhancement of acute dependence. Experiment 2b revealed that the shock parameters used in these studies can induce a hypoalgesic response on the test that is opioid mediated. These findings are discussed with regard to the neuroanatomy of fear systems as they relate to the neuropharmacological study of opioid withdrawal.

Enhancement op morphine analgesia in rats following removal from contextual conditioned fear cues

1. Previous studies have shown that morphine analgesia is enhanced when analgesia testing is conducted in an environment that has been previously paired with shock, but not in a novel or neutral environment. 2. Two experiments were conducted to assess if enhanced morphine analgesia could be demonstrated in a neutral context if rats were first exposed to conditioned fear cues. This was done by pre-exposing rats to a context previously paired with shock and testing for enhanced morphine analgesia in a neutral context immediately following removal from the conditioned fear context. To determine if conditioned analgesia contributed to the enhanced morphine analgesia, rats were tested for analgesic responsiveness immediately following removal from conditioned fear cues, prior to morphine administration. 3. In Experiment 1, although conditioned analgesia was not observed, a small enhancement of morphine analgesia was demonstrated in an neutral context in rats pre-exposed to conditioned fear cues, compared to non-conditioned controls. 4. In Experiment 2, which employed more sensitive test procedures, a strong enhancement of morphine analgesia was observed in a neutral context only in those rats that demonstrated conditioned analgesia.

Opiate withdrawal-like behavior induced by naloxone following exposure to a contextual fear stimulus

Abstract 1. 1. Considerable experimental attention has been directed at understanding the role of opioid peptides in mediating stress effects. Fewer studies have utilized non-physical or ‘psychological’ methods to investigate the role of the opioid system in stress. 2. 2. Recent studies have shown that conditioned fear, a psychological stressor, can augment morphine induced analgesia and acute dependence. Two experiments were conducted to assess withdrawal-like behavioral changes induced by the general opioid antagonist naloxone, in the absence of morphine, following exposure to a context conditioned fear stimulus. 3. 3. Experiment 1 demonstrated that a high dose of naloxone (10 mg/kg) produced a specific increase in one behavioral index of negative affect, forepaw tremor behavior, in rats exposed to a context fear stimulus. 4. 4. Experiment 2 assessed the relative effects of several naloxone (0, 1, 5, 10 mg/kg) doses in inducing withdrawal-like behavioral changes in animals exposed to a conditioned fear context. This experiment revealed that low doses of naloxone produced an overall increase in all behaviors. High naloxone doses tended to increase only forepaw tremor behavior. 5. 5. The results are discussed ih terms of opioid systems and stress.