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  • 1
    ISSN: 1432-2072
    Keywords: Key words Morphine ; Opioid receptor ; NMDA ; Tolerance ; Rat ; Tail flick
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Rationale: Pairings of a sweet taste and injection of morphine result in a learned avoidance of that taste and learned analgesic tolerance. This avoidance is mediated by the drug’s peripheral effect, while learned tolerance involves activation of N-methyl-d-aspartate (NMDA) receptors. Exposure to a sweet taste also reduces morphine analgesia. We studied whether this taste-mediated reduction was reversed by an NMDA or peripheral opioid receptor antagonist. Objectives: To determine whether an intraoral infusion of saccharin would modulate morphine analgesia in rats, and to study the contribution of NMDA as well as peripheral opioid receptors to this modulation. Methods: Six experiments used the rat’s tail-flick response to study the effect of an intraoral infusion of a sodium saccharin solution on morphine analgesia, and the effects of the quaternary opioid receptor antagonist methylnaltrexone as well as the non-competitive NMDA receptor antagonist MK-801 on this modulation of analgesia. Results: An intraoral infusion of saccharin reduced the analgesic effects of an intraperitoneal (i.p.) injection of morphine across a range of doses (experiment 1a), which was not attributable to an influence on tail-skin temperature (experiment 1b). This reduction was mediated by opioid receptors in the periphery and activation of NMDA receptors because morphine analgesia was reinstated by an i.p. injection of either methylnaltrexone (experiment 2a) or MK-801 (experiment 3a), which was not due to the effect of methylnaltrexone (experiment 2b) or MK-801 (experiment 3b) on morphine analgesia in the absence of saccharin. Conclusions: These results document evidence for an antagonism of morphine analgesia by actions of the drug at peripheral opioid receptors and excitatory amino-acid activity at NMDA receptors. They are discussed with reference to the aversive motivational effects of peripheral opioid receptors and pain facilitatory circuits.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-2072
    Keywords: Midazolam ; Hypoalgesia ; Fear ; Novelty ; Hot-plate ; Naloxone
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract 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.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-2072
    Keywords: Formalin test ; Hypoalgesia ; Fear ; Novelty ; Conditioning ; Midazolam ; Naloxone
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract 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.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Psychopharmacology 103 (1991), S. 177-182 
    ISSN: 1432-2072
    Keywords: Naloxone ; Analgesia ; Hypophysectomy ; Adrenalectomy ; ACTH ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract 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.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-2072
    Keywords: Stress ; Anxiety ; Rat ; Metabolism ; Energy expenditure ; Energy substrate utilisation ; Respiratory quotient ; Midazolam ; FG-7142 ; RO 15-1788 ; Panic ; Hyperventilation ; Sympathetic nervous system ; Benzodiazepine ; Conditioned stimulus ; Respiration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract 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 × 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 footshock (20 × 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.
    Type of Medium: Electronic Resource
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