Biomedical subjects

R F Westbrook

Publications and source records attributed to R F Westbrook.

At least 37 records · Page 2Linked to original sources

PubMed1997

Cognitive deficits in patients suffering from chronic fatigue syndrome, acute infective illness or depression.

BACKGROUND: Patients with chronic fatigue syndrome (CFS) report neuro-psychological symptoms as a characteristic feature. We sought to assess cognitive performance in patients with CFS, and compare cognitive performance and subjective workload experience of these patients with that of two disease comparison groups (non-melancholic depression and acute infection) and healthy controls. METHOD: A computerized performance battery employed to assess cognitive functioning included tests of continuous attention, response speed, performance accuracy and memory. Severity of mood disturbance and subjective fatigue were assessed by questionnaire. RESULTS: All patient groups demonstrated increased errors and slower reaction times, and gave higher workload ratings than healthy controls. Patients with CFS and non-melancholic depression had more severe deficits than patients with acute infection. All patient groups reported more severe mood disturbance and fatigue than healthy controls, but patients with CFS and those with acute infection reported less severe mood disturbance than patients with depression. CONCLUSIONS: As all patients demonstrated similar deficits in attention and response speed, it is possible that common pathophysiological processes are involved. The differences in severity of mood disturbance, however, suggest that the pathophysiological processes in patients with CFS and acute infection are not simply secondary to depressed mood.

Acute Disease↗

PubMed1997

Bacterial lipopolysaccharides induce peripheral nerve disturbances in rats that mimic human immune-mediated polyneuropathies.

A single injection of Escherichia coli lipopolysaccharide (LPS; i.v. and i.p.) reliably induced peripheral nerve disturbances in male Australian albino Wistar (AaW) rats. Signs developed 6 to 24 h after LPS inoculation and persisted only transiently. Most AaW rats had variable degrees of bilateral hind limb impairment, and rarely had forelimb, tail, or central impairment. Signs included gait abnormalities, proprioceptive loss, and to a lesser extent hind limb weakness and sensory deficits. Signs were more severe in male than female AaW rats and were induced in a number of genetically related rat strains (e.g., AaW and outbred Wistar and inbred Lewis rats, but not Sprague Dawley or inbred Fischer 344 rats). Development and severity of these signs were found not be related to animal body weight, but were dependent on LPS dose. Signs were not associated with LPS-induced alterations in pain perception, or occurrence of spontaneous pain, as indexed by tail-flick and hot-plate tests. Taken together, these data indicate that LPS induced transient peripheral nerve disturbances in rats, the severity of which was influenced by genetic, sex-related, and dose-related factors.

Animals↗

PubMed1996

Midazolam impairs the acquisition of conditioned analgesia if rats are tested with an acute but not a chronic noxious stimulus.

Three experiments investigated the effects of midazolam on acquisition of fear-mediated analgesic responses in rats conditioned on the heated floor of a hot-plate apparatus. Experiment 1 demonstrated that a moderate dose (1.25 mg/kg) of midazolam administered prior to conditioning impaired acquisition of conditioned analgesia in rats retested on the heated floor 24 h later. This effect of midazolam was reversed by the benzodiazepine receptor antagonist flumazenil. In contrast, in Experiment 2, the same or higher (2.5 mg/kg) dose of midazolam did not appear to affect the acquisition of conditioned analgesia in rats tested 24 h later with a formalin-injected paw on the non-heated floor of the hot plate apparatus. By testing rats with the opioid antagonist naloxone, Experiment 3 revealed that the higher dose of midazolam did disrupt the acquisition of conditioned analgesia in rats tested with formalin, but only by preventing acquisition of an immediate but brief analgesic response that was insensitive to naloxone. Midazolam was shown to have no effect on the acquisition of the enduring naloxone-reversible analgesia. These results are discussed in terms of benzodiazepines acting within the amygdala to produce a retrieval deficit whereby fear conditioning that takes place under the influence of a benzodiazepine can only be accessed if the animal is tested in the presence of ongoing noxious stimulation.

Animals↗

PubMed1995

Effects of benzodiazepine microinjection into the amygdala or periaqueductal gray on the expression of conditioned fear and hypoalgesia in rats.

Four experiments studied the effects of an intracranial microinjection of a benzodiazepine (midazolam) on the expression of conditioned fear (measured as passive avoidance) and conditioned hypoalgesia in rats. Unilateral microinjection of midazolam into the basolateral amygdala reduced both hypoalgesic and avoidance responses, whereas unilateral microinjection of midazolam into the ventrolateral region of the periaqueductal gray (vlPAG) reduced the hypoalgesic response but not the avoidance response. The results are discussed in terms of gamma-aminobutyric acid-ergic inhibition of antinociceptive mechanisms in the vlPAG and of the activation of these mechanisms by amygdala-based fear processes.

Amygdala↗

PubMed1995

Fos expression in the spinal cord is suppressed in rats displaying conditioned hypoalgesia.

Two experiments used c-fos expression as a marker of spinal nociceptive processing to study the neural correlates of hypoalgesic responses to conditioned stimuli (CSs) paired with an aversive event. Immunoreactive (ir) neuronal labeling of Fos, the nuclear protein encoded by the c-fos gene, was examined in the spinal cords of rats killed 2 hr after injection of dilute formalin into a hind paw. Compared with control rats either not conditioned or conditioned in one environment but tested elsewhere, there were significantly fewer Fos-ir neurons in the spinal cords of rats displaying hypoalgesic responses when tested in the presence of aversive CSs. Naloxone abolished hypoalgesic responses and reinstated spinal Fos expression, indicating that aversive CSs activated opioid-based antinociceptive mechanisms. The results confirm that aversive CSs produce hypoalgesia by inhibiting the transmission of ascending nociceptive information.

Animals↗

PubMed1995

Effects of a microinjection of morphine into the amygdala on the acquisition and expression of conditioned fear and hypoalgesia in rats.

A unilateral microinjection of morphine into the amygdala impaired the acquisition of fear and hypoalgesic responses in rats exposed to a heated floor in a hot-plate apparatus. This impairment was dose dependent, receptor specific, and not observed in rats microinjected with morphine into the caudal basolateral amygdala. A microinjection of morphine into the amygdala reduced the expression of fear responses and of naloxone-sensitive hypoalgesic responses, but did not reduce the expression of naloxone-insensitive hypoalgesic responses. The results document an involvement of opioidergic mechanisms in the amygdala in learned danger and of the amygdala in the control of opioid hypoalgesic responses. They also suggest that learned danger can activate antinociceptive mechanisms independently of the amygdala.

Amygdala↗

PubMed1995

Extinction of within-event learning is contextually controlled and subject to renewal.

Five experiments examined within-event learning in rats by inducing an appetite for one of the elements (salt) of a compound stimulus and assessing preference for the other element (almond). Almond preference was conditional upon (1) the almond flavour having been presented in compound with the salt, and (2) the assessment being conducted when the rats were out of sodium balance (Experiment 1). Presentations of the compound in one environment (A) and of the salt and almond elements in a second environment (B) resulted in greater almond preference when rats were tested in A than in B (Experiment 2). Almond preference was reduced when separate presentations of the compound and almond (Experiment 3) or of the compound and salt (Experiment 4) occurred in the same environments but not when these presentations occurred in different environments. Rats exposed to the compound in A and then extinguished to the elements in either A or B showed a reduced almond preference when tested in the extinction environment, but not when tested in the other environment (Experiment 5). Thus, extinction of within-event learning is context-specific and subject to renewal. The results were interpreted in terms of an associative model whereby separate presentations of the elements result in a symmetrical inhibitory link which is contextually gated (Bouton, 1993).

Animals↗

PubMed1994

Effects of midazolam and naloxone in rats tested for sensitivity/reactivity to formalin pain in a familiar, novel or aversively conditioned environment.

Rats tested for sensitivity/reactivity to formalin-induced pain in either an aversively conditioned or a novel environment displayed immediate but transient hypoalgesic responses that were insensitive to either a benzodiazepine (midazolam) or an opioid antagonist (naloxone). Exposure to the aversively conditioned, but not to the novel environment also provoked a more enduring hypoalgesic response that was abolished by either midazolam or naloxone. The results were taken to mean that fear is sufficient but not necessary for the production of hypoalgesic responses to environmental stimuli.

Analgesia↗

PubMed1994

Stress-induced changes in respiratory quotient, energy expenditure and locomotor activity in rats: effects of midazolam.

Changes in O2 consumption, CO2 production and locomotor activity were examined in rats exposed to (1) brief footshock, (2) an aversive conditioned stimulus (CS) predicting footshock, or (3) the anxiogenic drug FG-7142. Respiratory quotient (RQ = CO2 produced/O2 consumed) and energy expenditure [EE = O2 consumed (364 + 113RQ)] were derived to give an estimate of the energy substrate (fat, carbohydrate or protein) being utilised and total substrate oxidation respectively. In experiment 1, footshock (4 x 5 s 0.6 mA shocks over 2 min) produced an immediate increase in RQ, EE and activity. The RQ and EE effects were attenuated by the benzodiazepine midazolam (1 mg/kg). In experiment 2, an aversive CS, consisting of flashing light and buzzer that had 24 h earlier been repeatedly paired with foot-shock (20 x 5 s 0.6 mA shocks) caused a pronounced drop in RQ, an increase in EE and locomotor activity suppression. The effects of the aversive CS on RQ and EE were reversed by midazolam (1 mg/kg). In experiment 3, FG-7142 (10 mg/kg) produced a steep drop in RQ that persisted for at least 2 h and which was reversed by midazolam (1 mg/kg) and delayed by the benzodiazepine antagonist RO 15-1788 (10 mg/kg). FG-7142 also tended to inhibit EE and locomotor activity, but these effects did not reach statistical significance. Overall, these data show that stress causes profound alterations in RQ, EE and activity and that the pattern of change in these parameters differs with the nature of the stressor involved.

Animals↗

PubMed1994

Effects of the interval between exposure to a novel environment and the occurrence of shock on the freezing responses of rats.

Rats were exposed to a novel environment (E1) at time T1, given a footshock at time T2, and tested for freezing in E1 or in a second environment (E2). The function relating freezing to the T1-T2 interval among rats tested in E1 was an inverted U-shape. Rats exposed to short T1-T2 intervals displayed just as much freezing in E2 as in E1, whereas rats exposed to longer intervals froze less in E2 than in E1. These differences between the freezing responses in E1 and in E2 were obtained when the T1-T2 intervals were varied, but time spent in the shocked E1 was equated. Rats given two shocks in E1 differentiated between E1 and E2 when the initial shock occurred some time after exposure to E1, but not when the initial shock was presented shortly after that exposure. Rats shocked some time after exposure to E1 on Day 1 and shortly after exposure to that environment on Day 2 differentiated between E1 and E2 more than did rats exposed to the reverse sequence of T1-T2 intervals. The results were attributed to the formation of a network of connections among the E1 cues in rats exposed to moderate or long T1-T2 intervals, and to an impairment in the formation of this network as a result of the conditioning of a subset of cues in rats exposed to short T1-T2 intervals.

Animals↗

PubMed1994

The NMDA receptor antagonist MK-801 blocks acquisition and extinction of conditioned hypoalgesic responses in the rat.

The role of the N-methyl-D-aspartate (NMDA) receptor in Pavlovian conditioning of hypoalgesic responses in the hotplate apparatus was examined using the non-competitive NMDA antagonist MK-801. Either MK-801 or saline were administered before the training phase, test phase, or both, and MK-801 disrupted the acquisition and extinction but not the expression of conditioned hypoalgesic responses. All rats received counterbalanced injections of both MK-801 and saline after the training phase, therefore the learning decrements could not be attributed to a delayed, non-specific action of the drug. MK-801 did not augment paw-lick latencies on either the training or test days, indicating that its behavioural effects are not due to alterations in nociceptive sensitivity or motor performance. Similarly, MK-801's effects upon acquisition and extinction could not be attributed to state-dependent generalization decrement or impairments in processing of the hot-plate apparatus cues during training, as rats displayed normal hypoalgesic responses when tested with MK-801, and MK-801-treated animals displayed normal habituation of novelty-induced hypoalgesia in the hot-plate apparatus. These data suggest that the NMDA receptor system is involved in the acquisition and extinction, but not the expression of conditioned hypoalgesia and parallels the effects of NMDA receptor antagonists on the acquisition and expression of long-term potentiation (LTP) both in vitro and in vivo. It is plausible that an endogenous NMDA-mediated form of LTP plays a vital role in the acquisition and storage of aversive representations mediating conditioned hypoalgesic responses.

Animals↗

PubMed1993

Low and high doses of midazolam differentially affect hypoalgesia in rats conditioned to a heat stressor.

These experiments examined the effects of a benzodiazepine (midazolam) on rats' sensitivity-reactivity to the heated floor of a hot-plate apparatus. Rats were either previously exposed to the heated floor, or naive to the hot-plate apparatus, while control rats were familiarized with the apparatus in the absence of pain. A low dose (0.63 or 1.25 mg/kg) of midazolam attenuated the conditioned hypoalgesic response resulting from pre-exposure to a heated floor, but did not affect the hypoalgesic response elicited by exposure to a novel hot-plate apparatus nor the "baseline" sensitivity-reactivity among control rats. A high dose (2.5 mg/kg) of midazolam resulted in a naloxone-insensitive increase in both the conditioned and the novelty-induced hypoalgesia, and provoked a small, but naloxone-reversible increase in paw-lick latencies among control rats. The results were taken to mean that exposure to the heated floor results in hypoalgesic responses as a consequence of fear conditioning and the reinstatement of novelty. Midazolam was assumed to attenuate conditioned hypoalgesia by reducing fear but at the high dose to augment the hypoalgesic effects of novelty.

Analgesia↗

PubMed1993

Naloxone-induced hypoalgesia: evidence from the formalin test.

Two experiments examined the hypoalgesic effects that accrue from pairing exposure to a heat stressor with the opioid antagonist naloxone. Experiment 1 confirmed that rats given separate exposures to a heated floor and to naloxone are hypoalgesic when then tested on that floor. Further, the results confirmed that pairing the initial exposure to the heat stressor with naloxone resulted in a more profound hypoalgesic response. Experiment 2 provided new evidence for the hypoalgesic effects of separate exposures to the heat stressor and to naloxone, and for naloxone's enhancement of acquisition of the hypoalgesia, in rats tested for responsiveness to formalin. These results, therefore, demonstrate generalisability of the hypoalgesic effects across assays for acute and chronic pain.

Animals↗

PubMed1993

Effects of exposure to a to-be-shocked environment upon the rat's freezing response: evidence for facilitation, latent inhibition, and perceptual learning.

Three experiments used the freezing response of rats to examine the effects of pre-exposure to an environment upon (1) its associability with shock and (2) its discriminability from a second environment. Experiments 1 and 2 demonstrated that freezing was proportional to the interval between exposure to the environment at time T1 and the occurrence of shock at T2. This function was shifted by pre-exposure to the to-be-shocked environment, with brief pre-exposures increasing (facilitation) and extended pre-exposures decreasing (latent inhibition) the impact of a given T1-T2 interval on freezing. Experiment 3 provided evidence that the facilitatory and latent inhibitory effects resulting from brief and extended exposures to the to-be-shocked environment were accompanied by an increase in discriminability. The results were taken to have supported the claim that pre-exposure changes associability as well as discriminability (Hall & Honey, 1989) and were discussed in terms of the model for perceptual learning proposed by McLaren, Kaye, and Mackintosh (1990).

Animals↗

PubMed1992

Effects of an infusion of morphine into the accumbens nucleus upon acquisition of hypoalgesic and fear responses in rats exposed to a heart stressor.

Four experiments examined the effects of an infusion of morphine into the accumbens nucleus upon the aversive conditioning that can occur in rats exposed to the heated floor of a hot-plate apparatus. An infusion of morphine into the accumbens nucleus but not into the caudoputamen or into the prefrontal cortex impaired the acquisition of a conditioned hypoalgesic (Experiment 1) and fear (Experiment 4) response. This impairment was dose-dependent (Experiment 2) and mediated by opioid receptors in the accumbens nucleus, because it was removed by a systemic (Experiment 3a) or by an accumbal (Experiment 3b) infusion of naloxone. The results were attributed to an antagonism between the reinforcement process for aversive conditioning and the appetitive properties of an accumbal infusion of morphine.

Analgesia↗

PubMed1992

Conditioned tolerance to morphine hypoalgesia: compensatory hyperalgesia in the experimental group or conditioned hypoalgesia in the control group?

Five experiments used rats to examine the role of noxious stimulation in the development of contextually controlled morphine hypoalgesic tolerance and in the mediation of this tolerance by an associated hyperalgesic response. There was evidence for contextually controlled tolerance to morphine's hypoalgesic effects and an associated hyperalgesic response in rats injected with morphine and trained with noxious stimulation, but not in rats repeatedly exposed to morphine in the absence of that stimulation (Experiments 1 and 5). Latent inhibition (Experiment 2) and extinction (Experiment 3) of tolerance also depended upon pairing drug-related cues with noxious stimulation. The level of sensitivity-reactivity to noxious stimulation in morphine-tolerant rats tested with the drug was related to the intensity of the noxious stimulation that had been paired with the test context (Experiment 4). The results were interpreted to mean that some of the evidence for a Pavlovian involvement in tolerance development can be explained in terms of morphine's interference with the acquisition, but not with the expression of the hypoalgesic response otherwise acquired by cues paired with noxious stimulation.

Animals↗

PubMed1992

Potentiation by a taste of toxicosis-based context conditioning: effects of varying the test fluid.

Rats that drank water in a distinctive environment and were then injected with lithium chloride (water-lithium condition) were compared with those given an added taste on those conditioning sessions (sucrose-lithium condition). In three experiments this taste potentiated a conditioned aversion to the context, as measured by suppression of intake of another solution: either a novel sour taste (Experiments 1 and 2) or a familiar saline solution (Experiment 3). In contrast, this potentiation effect was not detected when subjects were tested with water, whether a high or low dose of lithium was used (Experiment 2). Instead, in Experiments 1 and 2 water-lithium subjects drank less water than did the sucrose-lithium subjects on such tests i.e. an apparent overshadowing effect, which was the opposite outcome to that found previously using almost identical procedures. Intake on recovery sessions in another context suggested that, when water is used as the test fluid, potentiation can be masked by two factors: a context-dependent aversion to water in water-lithium subjects, and a conditioned inhibition effect of water in sucrose-lithium subjects. These may account for previous failures to detect potentiation of context conditioning.

Animals↗

PubMed1991

Effects of hypophysectomy and adrenalectomy on naloxone-induced analgesia.

Experiment 1 demonstrated that pairings of the opiate antagonist, naloxone, with a heated floor came to induce analgesia, as indexed by the latencies with which rats licked their paws. This analgesia appears to be neurally mediated because it is unaffected by either hypophysectomy (experiment 2) or adrenalectomy (experiment 3). However, there was evidence for a pituitary involvement, as its removal potentiated the analgesic effect accruing from naloxone-stressor pairings.

Adrenalectomy↗