[The effect of mu-, delta- and kappa-opiate receptor agonists on the bioelectrical activity of the viscerosomatic convergent neurons in the posterior horn of the spinal cord]. / O vliianii agonistov mu-, del'ta- i kappa-opiatnykh retseptorov na bioélektricheskuiu aktivnost' vistserosomaticheskikh konvergentnykh neironov zadnego roga spinnogo mozga.

The effects of the mu-agonists morphine and DAGO, the delta-agonists D-Pen2, D-Pen5-enkephaline and dalargine and the kappa-agonists U50-488H and dynophine 1-17 on the activity of the spinal dorsal horn neurons receiving both cutaneous and visceral nociceptive inputs were studied. The experiments were performed under chloralose anesthesia in flaxedyl-immobilized rats. Morphine (10(-6)-10(-5) M) and DAGO (5 x 10(-7)-10(-6)) given pneumophoretically or topically onto the spinal cord suppressed the activity evoked by cutaneous nociceptive stimulation to a greater extent than those used by the nociceptive stimulation of the colon and rectum. Intravenous morphine (3-12 mg/kg) suppressed the activity caused by somatic and visceral stimulation to approximately the same extent. The delta-agonists D-Pen2, D-Pen5-enkephaline (10(-6)-10(-5) M) and delargin (10(-6)-10(-5) M) administered pneumophoretically or locally produced the effects similar to those of mu-agonists. All these effects were concentration-dependent and naloxone-sensitive. The kappa-agonists U50-488N (10(-4) M) and dynorphine (10(-4) M) failed to suppress the nociceptive responses of convergent neurons.

The NMDA-receptor antagonist dizocilpine (MK-801) suppresses the memory facilitatory action of thyrotropin-releasing hormone.

Thyrotropin-releasing hormone (TRH) has been shown to improve memory both in animal amnesia models and in humans. In an earlier study we have found that respiratory stimulant action of TRH is mediated through the N-methyl-D-aspartate (NMDA) receptors. Since brain NMDA receptors are implicated in neuronal plasticity, we have investigated whether the non-competitive NMDA antagonist dizocilpine antagonizes the memory-facilitatory action of TRH. TRH (5 mg/kg i.p.) increased passive avoidance scores in the rats in both memory retention and retrieval tests. Dizocilpine (0.2 mg/kg i.p.) caused no significant performance changes. However, it completely blocked the improvement of retention caused by TRH and reversed its effect on retrieval. We conclude that the facilitatory effect of TRH on avoidance retention and retrieval may be mediated by NMDA receptors.

[Viscerosomatic convergence on the lumbar interneurons of the dorsal horn of the spinal cord in cats and rats]. / Vistserosomaticheskaia konvergentsiia na liumbalnykh interneironakh dorsal'nogo roga spinnogo mozga u koshek i krys.

It is shown in experiments on spinalized cats under electrical stimulation of the pelvic nerve branch innervating the rectum as well as of the fibular nerve that 12 of 30 studied neurons to which the effect of these sources was converged were activated both by A- and by C-fibers. Reactions on stimulation of the fibular nerve were, apparently, mediated by the fibers with the conduction velocity not less than 2.2 m/sec. It is detected in experiments on spinalized rats that tension of the lower sections of the large intestine may evoke activation of neurons of the IV-V layers and inhibition of cells from the deeper layers. The inhibition evoked by the visceral stimulation in seven cases from 18 was provided by the effect directly on the postsynaptic membrane of these cells, in 11 cases it was localized in presynaptic (relative to them) structures. Naloxone, strychnine and atropine did not eliminate this inhibition which testifies against possible participation of opioids, glycines and acetylcholine in its creation. phaclofen, a blocker of the GABAB-receptors was also uneffective while bicuculline suppressed this inhibition in three cases from 12 which testifies to a probability of its participation in creation of GABAA-receptors.

Stimulant effect of thyrotropin-releasing hormone and its analog, RGH 2202, on the diaphragm respiratory activity, and their antagonism with morphine: possible involvement of the N-methyl-D-aspartate receptors.

Thyrotropin-releasing hormone (TRH) was reported to stimulate respiration and abolish the respiratory depressant effect of morphine-like analgesics. Some TRH analogs which have a diminished hormonal activity may be of interest as potential non-specific opioid antagonists. The mechanism of this effect of TRH and its analogs is still unclear. Thus, in the present work the respiratory stimulant effect of TRH and its analog RGH 2202 was studied in the urethane-anesthetized vagotomized artificially-ventilated rats. The integrated diaphragmatic electromyogram was used to evaluate the effects of the drugs. TRH and RGH 2202 administered either i.v. or directly onto the dorsal medullary surface significantly increased the respiratory activity of the diaphragm. TRH and RGH 2202 also effectively antagonized the diaphragm activity depression caused by morphine. The latency, time course and activity of RGH 2202 turned out to be close to those of TRH. The possible involvement of N-methyl-D-aspartate (NMDA) receptors in the mechanism of action of TRH and RGH 2202 was also investigated. It was shown that the non-competitive NMDA antagonists ketamine and MK-801 and the competitive antagonist D-amino-5-phosphonovalerate after local or i.v. administration prevented or discontinued the diaphragm activity stimulation by TRH and RGH 2202. Moreover, they blocked the antagonistic action of TRH and RGH 2202 on the morphine-induced diaphragm activity depression. Thus, we conclude, that TRH and RGH 2202 cause similar stimulant effects on the respiratory activity of the diaphragm and effectively antagonize its depression by morphine. These effects are likely to be mediated by the NMDA receptors located in the central respiratory structures.

[The mediator spectrum of the action of morphine and the pentapeptide FK 33-824 on the neurons of the cerebral cortex]. / O mediatornom spektre deistviia morfina i pentapeptida FK 33-824 na neirony kory golovnogo mozga.

Morphine and pentapeptide FK 33-824 were shown to reduce spontaneous and evoked neuronal discharges in the IInd somatosensory zone of the cortex on microiontophoretic and intravenous administration of cats. The neurons were identified by electric stimulation of thalamocortical fibers. The agents tested decreased neuronal responses to glutamate and acetylcholine. They failed to change responses to dopamine and enhanced responses to GABA. Morphine and pentapeptide FK 33-824 appeared to decrease slightly the inhibitory neuronal action of serotonin on microiontophoretic administration and increased it when injected intravenously. Beta-adrenoblocker propranolol decreased the inhibitory action of morphine and pentapeptide FK 33-824 on the cortical neurons.

[The possible participation of N-methyl-D-aspartate receptors in the stimulating action on respiration of thyroliberin and its analog RGH 2202]. / Vozmozhnoe uchastie retseptorov N-metil-D-aspartata v stimuliruiushchem deistvii na dykhanie tiroliberina i ego analoga RGH 2202.

The effects of ketamine and an antagonist of N-methyl-D-aspartate receptors dibenzocyclohepteniline maleate (MK-801) on the changes in the bioelectrical activity of the diaphragm induced by thyroliberine and its analogue L-pyro-2-aminoadipil-L-leucyl-proline amide (RGH 2202) were studied in experiments on vagotomized urethane-anesthetized rats. It was shown that ketamine (5 mg/kg, intravenously) and MK-801 (1 mg/kg, intravenously) eliminate and prevent an increase of the index of pulmonary ventilation caused by thyroliberine (5 mg/kg, intravenously) and RGH 2202 (5 mg/kg, intravenously). The data obtained suggest the involvement of N-methyl-D-aspartate receptors in the mechanism of the stimulating effects of thyroliberine and its analogue on respiration.

[Possibilities of the pharmacologic regulation of potassium channel function]. / O vozmozhnostiakh farmakologicheskoi reguliatsii funktsii kalievykh kanalov.

Potassium channels of excitable membranes are a heterogeneous group of channels among which one can distinguish potential-dependent, Ca2+-dependent, receptor-dependent and others. The substances contributing to the activation of these channels decrease excitability of membranes and the substances suppressing the activity of potassium channels increase it. A number of agents (narcotic analgetics, ligands of sigma-opiate receptors, GABA -mimetics, M-cholinergic agent) might modulate the activity of potassium channels indirectly through the corresponding receptors. Also, some drugs used in medical practice exert the immediate effect on these channels. Among them there are myotropic hypotensive drugs diazoxide, pinacidyl, BRL 34915 and minoxydyl, antidiabetic agents -- the derivatives of sulfon urea (butamide). The transfer of potassium ions through membranes is probably one of the fundamental mechanisms of the action of pharmacological agents.

[Neurotropic effects of tranquilizers administered intrathecally]. / Issledovanie neirotropnykh éffektov riada trankvilizatorov pri ikh intratekal'nom vvedenii.

The effects of intrathecally administered benzodiazepines diazepam, flurazepam and flunitrazepam on the pain thresholds in rats were studied by using chronically implanted catheters. Despite benzodiazepine-induced marked muscle relaxation and sedative effect, benzodiazepines produced no significant changes in the thresholds during tests of tail flick and paw compression whereas morphine was effective in both tests. Experiments with 14C-diazepam and 3H-flunitrazepam showed that after intrathecal administration these substances rapidly enter the brain. It was found that 10-15 minutes after intrathecal administration 3H-flunitrazepam concentration in the frontal parts of the brain is 1/4 of its concentration in the lumbar spinal cord. The data suggest that these benzodiazepines possess no antinociceptive activity at intrathecal administration to rats and that way of administration fails to prevent their action on the brain.

[Study of magnet-controlled transport of curare-like preparations of diadonium and dipyronium in animal experiments]. / Izuchenie magnitoupravliaemogo transporta kurarepodobnykh preparatov diadoniia i dipironiia v éksperimentakh na zhivotnykh.

The experiments on cats have shown that liposomes containing ferrocolloid and neuromuscular blocking agents (diadonium or dipyronium) cause selective muscle relaxation in the animal limb placed into the magnetic field, compared to the control limb kept outside the field. This effect was not related to the action of the magnetic field per se on neuromuscular transmission or the potency of neuromuscular blocking agents not contained in liposomes, but was induced by the accumulation of magnet-controlled liposomes in the target limb. The use of magnet-controlled liposomes for diadonium and dipyronium transport to one of the animal limbs decreases their unfavourable effect on respiratory muscle function.

[Use of a magnetic field for guided transport of curare-like substances]. / Ispol'zovanie magnitnogo polia dlia napravlennogo deistviia kurarepodobnykh sredstv.

Magnetically carried microspheres were used to investigate whether the curare-like drugs can be selectively transported to the muscles of one of the limbs of the cat. Pyrocurine and diadonium incorporated in such microspheres primarily suppressed neuromuscular transmission in the limb placed in magnetic field as compared with the control placed outside the field. The use of magnetic microspheres cointaining pyrocurine and diadonium produced no changes in systemic arterial blood pressure, local blood flow, EEG or ECG. The method also diminished the respiratory depression produced by the curare-like substances when they are routinely used for body muscle relaxation.

[Effect of opioid peptides on the transmission of nociceptive excitation in the spinal cord afferent tracts]. / Vliianie opiatnykh peptidov na peredachu notsitseptivnogo vozbuzhdeniia v afferentnykh traktakh spinnogo mozga.

The effects of methionine-enkephalin, leucine-enkephalin and of their two synthetic analogs on nociceptive transmission in the afferent tract of the spinal cord were studied in anesthetized spinal rats. All the opioid peptides inhibited the bradykinin-induced discharges in axons of the ventrolateral tract. However, the preparations had dissimilar effects on spontaneous activity. Naloxone blocked the action of the opioids.

[Effect of narcotic analgesics of nociceptive transmission in the spinal cord]. / O vliianii narkoticheskikh anal'getikov na peredachu notsitseptivnogo vozbuzhdeniia v spinnom mozge.

The action of morphine, promedol, fentanyl and pentazocin on nociceptive transmission in the spinal cord was studied in unanesthetized spinal rats with the use of intraarterial injection of bradykinin. When used in the same doses, the opiates also reduced the firing of the axons of the ascending portions of the spinal cord. Naloxon rapidly antagonized the action of the narcotics.

[Effect of opiate peptides on interneuronal transmission in the spinal cord]. / O vliianie opiatnykh peptidov na mezhneironnuiu peredachu v spinnom mozge.

It has been shown that leucin- and methionine-enkephalins (200 microgram into the lateral brain ventricle), as well as synthetic opiate peptides FK 33-824 (2 mg/kg) and tetrapeptide (25 mg/kg) disturb the excitation transmission in the cat ventrolateral columns. The effects of opiate receptors was more pronounced in animals with the intact central nervous system as compared with spinal animals. Naloxone (1 mg/kg) eliminated the effect of opiate peptides.

[Antinociceptive effect of serotonin]. / Ob antinotsitseptivnom éffekte serotonina.

Chronic experiments on rats have shown that serotonin in a dose of 50-160 micrograms injected into the lateral ventricle of the brain raised the threshold of the vocalisating response of the animals to the stimulation of tail tissues by single electric impulses. Methisergide (0.5 mg/kg, i.p.), a blocker of serotonin receptors, prevented the development of the antinociceptive effect of serotonin. Naloxon (2 mg/kg, s. c.), a morphine antagonist, did not affect the antinociceptive effect of serotonin.