Depressant Effects Of Morphine Research Articles

Effects of morphine sulfate on medial bulboreticular response to peripherally applied noxious stimuli

The analgesic action of morphine sulfate and its related agents is thought to be due to an effect on the central nervous system (CNS). The mechanism of action and the site at which morphine exerts its analgesic effect remain unknown. Several reports in the literature have implicated the depression of neuronal activity in the spinal cord as a possible mechanism of morphine analgesia. Neurons in the region of the nucleus gigantocellularis in the brain stem which respond characteristically to peripheral noxious physiological and chemical stimuli or to noxious electrical stimuli have been demonstrated extensively. The action of morphine on the single-unit activity of neurons in n. gigantocellularis in response to peripherally applied noxious stimuli has not been previously reported. Response patterns of single neurons in n. gigantocellularis were recorded extracellularly with glass microelectrodes in unanesthetized, functionally decrebrate cats immobilized with pancuronium. Electrical noxious stimulation of the saphenous nerve evoked two classes of responses in n. gigantocellularis neurons: excitatory and inhibitory. The present study shows that morphine sulfate at analgesic doses of 1 to 2 mg/kg iv has a predominantly depressant action on the neuronal activity of both classes of neuronal responses from n. gigantocellularis. The depressant effects of morphine were reversed by naloxone (0.05 to 0.1 mg/kg, iv). This depression of neuornal activity in the nucleus may partially explain its analgesic action.

Evidence for involvement of central noradrenergic neurons in the cardiovascular depression induced by morphine in the rat.

Morphine caused in the anaesthetized rat reduction in brain noradrenaline (NA) turnover, hypotension and bradycardia, similarly to the antihypertensive, alpha-adrenergic agonist, clonidine. All effects of morphine were antagonized by naloxone, as well as the alpha-receptor antagonist, yohimbine. In contrast, naloxone did not affect the circulatory depression and reduction in brain NA utilization by clonidine which both previously have been found to be antagonized by yohimbine. In contrast to clonidine, morphine even in high doses did not facilitate the flexor reflex activity of acutely spinalized rats. Pretreatment with protriptylin largely attenuated the circulatory depressive effects of morphine, as it has previously been found to block the corresponding effects of clonidine. Thus, the morphine-induced cardiovascular depressive effects are primarily elicited by activation of opiate receptors. However, the inhibition of brain NA neurotransmission by morphine appears critically involved in the mediation of the circulatory depression.

Depressive effects of morphine upon lamina V cells activities in the dorsal horn of the spinal cat

The effects of morphine upon the transmission of nociceptive messages at the spinal level have been investigated in spinal cats by studying its effects on the activities of lamina V dorsal horn interneurons. Morphine (2 mg/kg i.v.) induced a direct depressive action at the spinal level, since it strongly reduced both spontaneous and evoked activities of lamina V cells. The spontaneous firing rate and the responses elicited by natural nociceptive stimulation were decreased by 50%. The responses of these units evoked by supramaximal electrical stimulation were reduced to 67% of their initial value; in this case, the depressive effect was much more prominent on the late component of the long duration responses. The observed depressive effects are specific since they are immediately reversed by administration of opiate antagonists (nalorphine or naloxone).

Respiratory Depressant Effects of Morphine on the Central Nervous System of the Infant Rat

The dose of morphine hydrochloride (1.5 mg/kg) necessary to achieve 50% depression of the ventilatory rates was identical in both 5- and 30-day-old rats. However, at equivalent blood levels, drug concentrations in the brain stem, cerebral hemispheres, and cerebrospinal fluid of the infant rat were approximately 2-fold greater than those found in the older animal. With increased doses (3 mg/kg), the respiratory rate of the infant rat decreased to 15% of resting values, in association with an increased rate of morphine accumulation in the cerebrospinal fluid. Although older rats showed only a 50% depression of the respiratory rate at doses as high as 6 mg/kg, the LD50 (16 mg/kg) was 73% lower than found for the infant animal. In the usual therapeutic dose range, the infant rat appears to be no more sensitive to the toxic effects of morphine than the older animal.

Effects of morphine on the hormonal control of metabolism—VII: Morphine-induced changes in sensitivity of the glucose-uptake system of muscle to extracellular calcium

The effects of morphine and of hydrocortisone on uptake of glucose from media of different calcium content by diaphragm of normal and of chronically morphinized rats have been studied in vitro. The rate of glucose-uptake by diaphragm from chronically morphinized rats, unlike that by diaphragm of normal rats, is not increased by omission of calcium from a standard medium containing 2.73 mM calcium, but it is depressed by a 2–5 fold increase in the calcium content of the medium. The stimulant effect of added morphine on glucose-uptake by normal rat-diaphragm is dependent upon the presence of calcium in the medium and is much increased by an increase of calcium in the medium. The depressant effect of morphine on glucose-uptake by chronically morphinized rat-diaphragm is but little affected by changes in calcium concentration of the medium from 0 to 5.46 mM. The depressant effect of added hydrocortisone on glucose-uptake by normal rat-diaphragm is unchanged by omission of calcium from the medium, but the stimulant effect on chronically morphinized rat-diaphragm is apparently calcium-dependent.

Interactions of morphine and nalorphine with physostigmine on operant behavior in the rat

Morphine and nalorphine were tested alone and in combination with physostigmine (0.0625 mg/kg) in rats trained under a continuous avoidance schedule with an escape contingency. When tested alone, nalorphine increased avoidance rate in doses up to 32 mg/kg but exerted no other effects. Morphine, 1 mg/kg, increased avoidance response rate while higher doses produced a graded depression of all behavior. In the presence of physostigmine, nalorphine produced a well-defined graded depression of avoidance responding and increased the number of shocks received by the animals over a 16-fold dose range. Physostigmine failed to potentiate the prominent depressant effects of morphine in the same test situation. The finding that in the presence of cholinesterase inhibition nalorphine acts as a depressant of operant behavior in the rat supports existing evidence that cholinergic mediation should be considered as a factor in some of the actions of strong analgesics.

The effects of chronic morphine administration on tooth pulp thresholds in dogs and cats.

SummaryThe effects of acute and chronically administered morphine on the threshold voltage required to elicit a response to tooth pulp stimulation in the dog and cat were quantitatively compared. A single dose of morphine elevated tooth pulp thresholds to a greater extent in dogs than in cats. After chronic administration, a decrease in the threshold occurred in cats but not in dogs. In the latter, a tolerance to (but not a reversal) of the threshold elevating effect was observed. Tolerance was seen to the overt depressant effects of morphine in dogs but not to the overt excitatory effects in cats. Studies concerned with attempts to delineate the reason (s) for these differences may be useful in advancing our knowledge concerning the mechanisms responsible for the analgesic effect of morphine and the development of tolerance to this drug.

Antagonism of Benzedrine to the Central Depressant Effects of Morphine

Antagonism of Benzedrine to the Central Depressant Effects of Morphine

Antagonism of Benzedrine to the Central Depressant Effects of Morphine.*

Antagonism of Benzedrine to the Central Depressant Effects of Morphine.*