Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0344307 (analgesia)
 28,200 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We observed that the spinal cord of rats was involved in development of tolerance and dependence to morphine that was administered systemically by s.c. morphine-pellet implantation. Rats, surgically fitted with intrathecal catheters, were injected intrathecally (i.t.) with saline or 2.4 nmol beta-chlornaltrexamine (beta-CNA), an irreversible opiate antagonist. Twenty-four h later, animals were implanted s.c. with either placebo or morphine pellets. Seventy-two h after implanting pellets, development of tolerance or dependence was assessed. Control animals implanted with morphine pellets became tolerant to analgesia induced by i.p. injections of morphine as determined by the use of tail flick and hot plate analgesic assays. beta-CNA pretreatment antagonized the effects of i.p. injections of morphine and blocked development of tolerance in morphine-implanted animals. Dependence was assessed by observing several characteristic signs of precipitated withdrawal. Treatment with beta-CNA before morphine treatment antagonized naloxone-induced expression of withdrawal for all signs observed, except weight loss. We conclude that the spinal cord plays a significant role in development of tolerance and dependence induced by systemically administered opiates.
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PMID:Spinal antagonism of tolerance and dependence induced by systemically administered morphine. 668 42

The analgesic effects of i.c.v. morphine and the enzyme-resistant enkephalin analogs, D-Ala2-Leu- and D-Ala2-Met-enkephalinamide, measured in the tail-flick test, were compared in nondependent and morphine-dependent rats. Dependence was induced and maintained by scheduled access to 0.05% morphine solution for at least 8 weeks before testing. In the nondependent rats, 1.0 to 10 micrograms of each drug injected into the lateral ventricle produced a dose-related increase in analgesia; on a molar basis, morphine was 1.3 (1.0-1.7) times more potent than the enkephalins. Naloxone (0.3 and 1.0 mg/kg) antagonized the analgesic effect of the three compounds: the effect of morphine was competitively antagonized, whereas the interaction between naloxone and the enkephalins did not appear to be competitive. Chronic morphine treatment produced different changes in the analgesic effects of morphine and the enkephalins. In contrast to the tolerance that was observed after s.c. injection of morphine in morphine-dependent rats, the analgesic effect of i.c.v. morphine was enhanced in these animals. The analgesic effect of D-Ala2-Leu-enkephalinamide was also enhanced in morphine-dependent animals, whereas tolerance developed to the effect of D-Ala2-Met-enkephalinamide. Thus, the analgesic effect of morphine and enkephalins are differentially altered in the presence of naloxone and in morphine-dependent animals. These results could reflect an allosteric interaction between neuronal binding sites for enkephalins and opiate alkaloids.
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PMID:Analgesic effects of intraventricular morphine and enkephalins in nondependent and morphine-dependent rats. 720 Oct 20

1. Differences between sexes and the effect of bilateral surgical gonadectomy on the response to morphine analgesia and dependence were examined in rats and mice. 2. The analgesic response to morphine (5 mg/kg) was assessed by the hot plate and the abdominal constriction tests. Dependence was induced by injecting morphine at increasing doses (5-160 mg/kg) for 6 consecutive days and withdrawal signs elicited by injecting naloxone (2.5 mg/kg). 3. The base line reaction times in the intact control, sham-operated and gonadectomized animals of either sex were not significantly different from each other. 4. After treatment with morphine, the percentage increase in the reaction time in gonadectomized male and female rats and in gonadectomized male mice was significantly higher than in their respective controls. 5. The increase in the reaction time, after morphine treatment, was significantly higher in gonadectomized female rats than in gonadectomized male rats. 6. Naloxone-induced withdrawal signs in morphine-dependent gonadectomized rats and mice were not significantly different from those in sham-operated controls. However, female rats in both groups exhibited a significantly higher number of escape jumping responses than males.
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PMID:Sex differences and the effect of gonadectomy on morphine-induced antinociception and dependence in rats and mice. 755 25

Dependence on opioids and the number of opioid overdose deaths are serious and escalating public health problems, but medication-assisted treatments for opioid addiction remain inadequate for many patients. Glucagon-like pepide-1 (GLP-1) is a gut hormone and neuropeptide with actions in peripheral tissues and in the brain, including regulation of blood glucose and food intake. GLP-1 analogs, which are approved diabetes medications, can reduce the reinforcing and rewarding effects of alcohol, cocaine, amphetamine, and nicotine in rodents. Investigations on effects of GLP-1 analogs on opioid reward and reinforcement have not been reported. We assessed the effects of the GLP-1 receptor agonist Exendin-4 (Ex4) on opioid-related behaviors in male mice, i.e., morphine-conditioned place preference (CPP), intravenous self-administration (IVSA) of the short-acting synthetic opioid remifentanil, naltrexone-precipitated morphine withdrawal, morphine analgesia (male and female mice), and locomotor activity. Ex4 treatment had no effect on morphine-induced CPP, withdrawal, or hyperlocomotion. Ex4 failed to decrease remifentanil self-administration, if anything reinforcing effects of remifentanil appeared increased in Ex4-treated mice relative to saline. Ex4 did not significantly affect analgesia. In contrast, Ex4 dose dependently decreased oral alcohol self-administration, and suppressed spontaneous locomotor activity. Taken together, Ex4 did not attenuate the addiction-related behavioral effects of opioids, indicating that GLP-1 analogs would not be useful medications in the treatment of opioid addiction. This difference between opioids and other drug classes investigated to date may shed light on the mechanism of action of GLP-1 receptor treatment in the addictive effects of alcohol, central stimulants, and nicotine.
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PMID:Glucagon-Like Peptide-1 Receptor Agonist Treatment Does Not Reduce Abuse-Related Effects of Opioid Drugs. 3105 14