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Biomedical subjects

E L Way

Publications and source records attributed to E L Way.

At least 145 records · Page 8Linked to original sources
PubMed1975

Regional sensitivity of the rat brain to the inhibitory effects of morphine on wet shake behavior.

The aim of this investigation was to determine the brain regions which were most sensitive to the inhibitory effects of morphine on the shaking response of pentobarbital-anesthetized rats to ice water. The median inhibitory dose (ID50) of morphine sulfate administered intraventricularly was found to be 0.35 mug/rat. When morphine was bilaterally injected into different regions of the brain, the ID50 values ranged from 0.04 to 17.9 mug/rat. The lowest ID50 values (0.04-0.20 mug) were found in the periaqueductal gray, the medial preoptic area and the locus ceruleus. The ID50 values ranged from 0.65 to 1.6 mug for areas around the nucleus accumbens, the fasciculus retroflexus, the medical thalamus and the septal area; from 5.6 to 7.3 mug for various hypothalamic nuclei; and from 11.0 to 17.9 mug for the basal ganglia, reticular formation substantia nigra and the reticular nucleus of the thalamus. The brain areas with the lowest ID50 values are known to have thermoregulatory functions. The similarity of the shaking response to shivering is discussed. It is concluded that the central inhibitory effects of morphine on shaking are subserved by discrete neuroanatomical substrates located in medial subcortical structures.

Anesthesia↗
PubMed1975

Brain acetylcholine and choline following acute and chronic morphine treatment and during withdrawal.

Levels of brain acetylcholine and choline were measured with a gas chromatograph in Swiss-Webster or ICR mice and Sprague-Dawley rats: a) 30 minutes after various single doses of morphine sulfate s.c.; b) rendered highly tolerant to and dependent on morphine by pellet implantation for 3 days; c) at various times after abrupt withdrawal (pellet removal); or d) during abstinence precipitated by the narcotic antagonist naloxone. The specific activity of brain acetylcholinsterase was determined in treatment d. Brain choline levels generally remained unaffected by the above manipulations. It was found that analgetic doses of morphine did not alter the steady-state levels of brain acetylcholine, but slight increases were observed after high doses and in morphine-tolerant animals. Abrupt withdrawal of morphine in the mouse caused a significant increase in brain acetylcholine levels, which was observed at 6 hours but not at 12 and 24 hours. In rats, abrupt withdrawal had no effect on acetylcholine levels at 6 and 18 hours. Nalonone-precipitated withdrawal significantly lowered the brain acetylcholine in both mice and rats without affecting acetylcholinesterase activity. This lowering was observed in animals that jumped after naloxone, but not in those failed to jump. It is concluded that this decrease in brain acetylcholine may be related to an increased neuronal release.

Acetylcholine↗
PubMed1975

Effects of divalent cations, cation chelators and an ionophore on morphine analgesia and tolerance.

The analgesic effect of morphine was antagonized in mice by intracerebroventricular injection of Ca++, Mg++ and Mn++ and was potentiated by ethylene glycol tetraacetic acid but was not altered by Sr++, Ba++, Ni++, Hg++, Cd++ or ethylenediamine tetraacetic acid. The antagonistic effect of Ca++ was not altered by pretreatment with pargyline or 6-hydroxydopamine indicating that altered release of catecholamines or serotonin was not involved in this action of Ca++. Induction of morphine tolerance by pellet implantation also did not alter the antagonistic effect of Ca++. The antagonistic effects of Ca++ and naloxone were additive in both nontolerant and tolerant animals and the apparent affinity of naloxone for its receptors, as estimated by in vivo pA2 determinations, was not altered by Ca++. However, the ionophore X537A was found to increase greatly the narcotic antagonist effect of a low dose of Ca++ although the ionophore alone did not alter the effects of morphine. This indicates that Ca"++ must penetrate cell membranes in order to reduce the analgesic effects of morphine. These findings indicate the importance of Ca++ localization in the actions of narcotic agonists and antagonists.

Analgesia↗
PubMed1975

Central sites of naloxone-precipitated shaking in the anesthetized, morphine-dependent rat.

Naloxone hydrochloride, an opiate antagonist, administered via the intracranial or parenteral route precipitates shaking behavior in the morphine-dependent rat. We made localized bilateral injections of naloxone HCl, 1.5 mug/rat, into 60 subcortical sites of the pentobarbital-anesthetized, morphine-dependent rat and found that two circumscribed areas of the brain, the medial hypothalamus and the periaqueductal-4th ventricular spaces, were selectively sensitive to naloxone-precipitated shaking. In the nondependent rat, morphine injections into the anterior diencephalon inhibited the shaking response to ice water; injections of morphine into the medial diencephalon were less effective. However, naloxone antagonized the morphine-inhibited shaking more effectively when injections of naloxone were made in the medial diencephalon than when injections were made in the anterior diencephalon. These results suggest that the reciprocal relationship of morphine and morphine-naloxone effects on shaking behavior may be regulated by topographically different structures in the diencephalon.

Animals↗
PubMed1975

Influence of L-tryptophan on morphine analgesia, tolerance and physical dependence.

Four hours after the acute administration of L-tryptophan (75 mg/kg) to either, nontolerant or morphine-tolerant mice, the antinociceptive effect of morphine was partially and significantly antagonized. Daily tryptophan administration to rats and mice during a 3-day morphine pellet implantation period increased the rates of both morphine tolerance development and development of physical dependence. The accelerating effect of tryptophan on tolerance and dependence development in mice was antagonized by pretreatment with the tryptophan hydroxylase inhibitor, p-chlorophenylalanine. Acute tryptophan administration (75 mg/kg) significantly increased mouse brain 5-hydroxytryptamine levels for at least 4 hours. Although chronic tryptophan treatment increased 5-hydroxytryptamine turnover in morphine-treated mice, no effect of chronic morphine or tryptophan treatment on the particulate tryptophan hydroxylase activity of whole mouse brain was observed. Slight increases in tryptophan hydroxylase activity were observed in the caudate-putamen and septal areas of rat brain 3 and 6 days, respectively, after s.c. morphine pellet implantation. These and previous studies from our laboratory indicate that the development of morphine tolerance and dependence can be modified by agents affecting serotonergic mechanisms.

Analgesia↗