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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Spinal reflexes in the rabbit are suppressed tonically by endogenous opioids. The contributions made to this suppression by mu-, delta- and kappa-opioid receptors have been investigated by studying the actions of a range of opioid antagonists and agonists on reflexes evoked by sural nerve stimulation in the ankle extensor gastrocnemius medialis (g.m.), and in the knee flexor semitendinosus (s.t.). When given at a total dose of 88.5 micrograms kg-1 i.v., either of the universal opioid receptor antagonists (-)-naloxone and (-)-quadazocine enhanced the g.m. response to more than 7 times the pre-drug control values, and the s.t. reflex to 1.5 times controls. The effects of quadazocine were stereospecific. The selective delta antagonist ICI 174864 (3.5 mg kg-1 i.v. total) also augmented the g.m. reflex but only to twice pre-drug controls. The mu-agonists fentanyl (100 micrograms kg-1) and morphine (50 mg kg-1) suppressed both g.m. and s.t. reflex responses to less than half control levels by a naloxone-reversible mechanism. The kappa-agonists bremazocine (50 micrograms kg-1 total), tifluadom (100 micrograms kg-1), ethylketocyclazocine (200 micrograms kg-1) and U50488H (1 mg kg-1) potentiated the g.m. reflex and had variable effects on the s.t. response. Naloxone usually added to the facilitatory actions of these drugs. kappa-Opioid receptor agonists also caused a profound, naloxone-reversible depression of arterial blood pressure. It may be concluded that the endogenous opioid-mediated suppression of spinal reflexes in the rabbit is mediated mainly, if not exclusively, through mu-receptors. There are no known endogenous ligands which are specific for the mu-receptor, so in the present case it seems that selectivity is determined by the receptor population rather than by the ligand.
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PMID:The contributions of mu-, delta- and kappa-opioid receptors to the actions of endogenous opioids on spinal reflexes in the rabbit. 303 45

The effects of enkephalin derivates with different opioid receptor subtype specificity and naloxone on cardiovascular responses and kallikrein-kinin system (KKS) were studied in anesthetized rats exposed to 30% hemorrhage. Administration of a mu-receptor agonist (DAGO) in early hemorrhage improved mean arterial blood pressure (MAP) responses to hemorrhage. This effect could be abolished by naloxone pretreatment. Moreover, a delayed MAP recovery after hemorrhage could be observed. Treatment with a delta-agonist (DADL) resulted in transient depression of MAP and heart rate (HR). Hemorrhage by itself caused only a slight activation of KKS as indicated by decreased plasma kallikreinogen concentration and reduced kallikrein inhibitor capacity after 20% blood loss. Enkephalin administration did not exert significant effects on KKS. Naloxone pretreatment, in contrast, induced prehemorrhagic activation of KKS, which was potentiated by subsequent hemorrhage. Naloxone-induced activation of KKS could be confirmed by an in vitro study. Taken together these results suggest that the KKS is not involved in MAP and HR responses to enkephalin administration during hemorrhage, whereas it might be implicated in naloxone-induced delayed posthemorrhagic MAP recovery.
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PMID:Effect of intravenous enkephalin administration on kallikrein-kinin system in experimental hemorrhagic shock. Evidence for activation of kallikrein-kinin system by naloxone. 307 Feb 4

Subcutaneous administration of the enkephalin analogue FK33-824 (FK) elicited a dose-related decrease in rectal temperature and respiratory rate in male ddY strain mice. Naloxone and 3 days' implantation of morphine pellet decreased the effects of FK, suggesting the involvement of opioid receptors and cross-tolerance with morphine to both effects of FK. A positive correlation was found between the FK-induced decrease in rectal temperature and that in respiratory rate among the 6 strains of inbred mice including BALB/c, C3H, A/J, CBA, C57BL/6 and DBA/2. The degree of hypothermia elicited by FK was different among strains, whereas marginal strain difference was seen in the respiratory depression induced by FK. The strain difference in the FK responses may be due to the difference in the opioid receptor subtypes in the brain.
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PMID:Effects of the enkephalin analogue FK33-824 on rectal temperature and respiratory rate in male mice. 322 53

From the evidence reviewed above, there is little doubt that ECS activates endogenous opioids and modifies their receptors. Thus, this form of SIA is accompanied by many other corollaries of opioid-like actions, including catalepsy, similar EEG patterns, common autonomic effects, and increases in opioid receptor binding sites. Investigations have further indicated that the amnestic effects of ECS can also be attenuated by naloxone, and that pituitary-derived opioids may play an important role as a predominant source of opioids that contribute to these opioid-like effects following ECS. It is hoped that these many attempts to correlate SIA with other behavioral and physiological endpoints following ECS will provide a more global perspective on the role of endogenous opioid systems in ECS. From these results, it is suggested that other forms of SIA may also share many of these properties in common with ECS-induced SIA. Nonetheless, ECS and other forms of SIA, such as cold water exposure and restraint, share with ECS a common history of clinical use in the treatment of human depression. It is possible that the common thread linking these experimental observations to endogenous opioid systems may provide new insights into the cause and treatment of mental disorders as well as the perception of pain.
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PMID:Electroconvulsive shock activates endogenous opioid systems: behavioral and biochemical correlates. 352 81

Opioid drugs in high doses can obtund the stress response to major surgery but only at the expense of marked cardiorespiratory depression. The postoperative hormonal response to surgical stress was measured in 20 patients undergoing hysterectomy who were given either meptazinol 100 mg or morphine 15 mg intramuscularly at the end of the surgery. Both drugs at the doses used failed to diminish the stress response. Those patients who received meptazinol showed elevated prolactin levels: this may be an indicator of agonist activity at the mu 1 opioid receptor.
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PMID:Influence of meptazinol on metabolic and hormonal responses following major surgery. A comparison with morphine. 399 81

The effect of morphine on the cutaneo-adrenal nerve reflex was studied in rats anesthetized with urethane-chloralose. Morphine (1 mg/kg, i.v.) significantly depressed the reflex increase in adrenal nerve activity induced by noxious lower chest pinching. Morphine (10 mg/kg, i.v.) significantly inhibited the reflex decrease in adrenal nerve activity induced by innocuous lower chest and hindlimb brushing, as well as the response induced by noxious lower chest pinching. Reversal by naloxone of the morphine-induced depression of the cutaneo-adrenal nerve reflexes indicates that the opioid receptor is associated with these effects of morphine.
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PMID:Effect of morphine on the adrenal sympathetic reflex elicited by mechanical stimulation of the skin in rats. 406 57

The prototype sigma opioid receptor agonist N-allyl-normetazocine (SKF 10,047) was injected into the third cerebral ventricle of conscious, unrestrained cats, and their temperature was monitored automatically from the retroperitoneal space. In a cold environment (0 degrees C) a small, but not dose-related, hypothermia occurred after doses of 100-500 micrograms. This response was not antagonized by naloxone given intraventricularly either 15 min before or 1 hr after the opioid. A smaller hypothermia resulted after 250 micrograms SKF 10,047 when the environmental temperature was 22 degrees C, whereas hyperthermia developed in a hot environment (34 degrees C). Thus SKF 10,047 appears to allow body temperature to drift, upward in the heat and downward in the cold, a pattern indicative of thermoregulatory depression. These results are similar to those obtained in the first 2-3 hr after pentazocine administration, and they support a previous classification of the initial temperature response to centrally injected pentazocine as due to stimulation of sigma opioid receptors.
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PMID:Central injection of a sigma opioid receptor agonist alters body temperature of cats. 626 55

The cardiorespiratory effects of prototype mu (morphine and beta-casomorphine 1-4) and delta (D-Ala2-D-Leu5Enkephalin-DADLE) opioid ligands were compared following microinjection into third and fourth ventricular spaces in conscious and anesthetized rats. The direction of change in arterial pressure produced by ventricular opioid injections varied according to ligand, site of administration, and state of consciousness of the animal. In general, pentobarbital anesthesia blocked or reversed the pressor response to these opiate agonists; depressor responses became magnified following pentobarbital. Qualitatively, the predominant effect of third ventricular DADLE in anesthetized rats was to produce a depression of arterial pressure and pulse pressure, suggesting an involvement of hypothalamic delta opioid receptors in decreasing sympathetic outflow. By contrast, morphine exerted pronounced bradycardic effects following fourth ventricular administration, suggesting an action at mu opioid receptors which influence vagal parasympathetic activity. Both ligands lowered respiratory rates upon fourth ventricular injection, indicating a possible involvement of either opioid receptor subtype in the depression of brainstem respiratory centers. These depressant effects of opioids upon cardiorespiratory function were readily reversed by naloxone. The qualitative similarity between the cardiovascular effects of third ventricular DADLE administration and various forms of circulatory shock may indicate that both phenomena involve delta opioid receptors at hypothalamic sites.
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PMID:Cardiorespiratory effects of mu and delta opiate agonists following third or fourth ventricular injections. 630 Aug 3

A new partial agonist-antagonist analgesic drug, dezocine, was evaluated in rats for its anesthetic potency using a MAC-reduction model. Respiratory effects as shown by changes in PaCO2 were also analyzed. A reduction of approximately 50% in cyclopropane MAC was found with doses of 6 mg/kg or more. This is the largest reduction for any drug of this class. PaCO2 levels increased up to 52 mm Hg with doses of dezocine up to 2 mg/kg. No evidence of reversal of respiratory depression or of further respiratory depression was found with increasing dosages. Combining dezocine with morphine resulted in a further reduction in cyclopropane MAC without a significant change in PaCO2. This suggests that dezocine acts primarily on the same receptor (mu) as morphine and that this receptor activity is further modulated by effects of dezocine on a second opioid receptor.
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PMID:Anesthetic potency of dezocine and its interaction with morphine in rats. 641 96

The use of naloxone (NAL), an opioid receptor antagonist, has provided indirect evidence that endogenous opioids contribute to cardiovascular depression during shock. To determine if endogenous opioids act centrally to influence cardiovascular function, injections of D-Ala2-Met-enkephalinamide (DAME), a potent Met-enkephalin analog, were made into the 3rd cerebral ventricle (ICV) of 5 conscious cynomulgus monkeys restrained in primate chairs. Systolic blood pressure (SBP) and heart rate (HR) were determined every 10 min during a 30-60 min control period and for up to 5 hr post-injection. Colonic temperature (Tc) was monitored continuously. SBP declined from baseline values with 50 and 100 micrograms (85.2 and 170.4 nM) doses but was significant (p less than 0.001) for only the 100 micrograms dose between 15-125 min post-injection. HR also decreased but did not exhibit any significant variation with time. However, when averaged across time, HR fell significantly (p less than 0.001) from baseline: -9.1 +/- 2.3 and -15.0 +/- 2.1 b/min for 50 and 100 micrograms DAME, respectively. Tc displayed a nonsignificant, delayed (greater than 2 hr) rise in Tc with the 50 micrograms dose, whereas the 100 micrograms dose caused a significant (p less than 0.001) decline in Tc (from 65-125 min post-injection). NAL injected ICV attenuated the effects of DAME but had no effect on SBP, HR or Tc when injected alone. Systemic injection of DAME (300 micrograms) in one monkey produced a transient decline in SBP (26 mmHg within 2 min) which returned to baseline values 4 min post-injection. HR and Tc were unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Autonomic effects of central injections of D-Ala2-Met-enkephalinamide (DAME) in the conscious monkey. 649 24


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