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K S Yakimova

Publications and source records attributed to K S Yakimova.

9 recordsLinked to original sources
PubMed2000

A post-ischaemic single administration of galanthamine, a cholinesterase inhibitor, improves learning ability in rats.

Transient forebrain ischaemia is widely observed in clinical practice. We have examined the effect of a single administration of the cholinesterase inhibitor galanthamine (2mg kg(-1) i.p.) 25 min after reperfusion in male Sprague-Dawley rats (180 +/- 20 g) after a 20-min common carotid artery occlusion. Twenty-four-hours post-ischaemia there was no difference in motor co-ordination or muscle tonus of the rats treated with or without galanthamine as assessed by the rota-rod test. Learning ability was examined using the shuttle-box test, evaluating the latency time and the number of errors for six days in succession. The performance of the ischaemic saline-injected rats was significantly impaired on days 4, 5, 6 (latency time) compared with the non-ischaemic rats and with the ischaemic animals administered galanthamine (P < 0.05). Similar results were obtained when counting the number of errors (failure to cross the cage during conditioned or unconditioned stimulus). The monitoring of body temperature during the first 12-h post-ischaemia did not show any significant difference between the groups. The data showed a beneficial effect of galanthamine on the recovery of learning ability when administered once only post-ischaemia. This suggests a direct effect on the early pathologic mechanisms of CNS damage. Cholinesterase inhibitors may prove useful in the early clinical treatment of ischaemic conditions.

Animals↗
PubMed1999

Effect of nociceptin and [Phe1psi (CH2-NH) Gly2]-nociceptin-(1-13)-NH2 on tonic activity of rat hypothalamic neurons.

The effect of nociceptin, an endogenous ligand for a unique member of the cloned opioid receptor family ORL1-receptor, on tonic activity of neurons in the preoptic area/anterior hypothalamus (PO/AH) has been examined in rat brain slices using extracellular recordings. Nociceptin (1, 10 and 100 nM) decreased dose-dependently tonic activity of PO/AH neurons. This effect was not significantly different from the effect of [Phe1psi (CH2-NH) Gly2]-nociceptin-(1-13)-NH2 (1, 10 and 100 nM), recently proposed as a selective antagonist of the nociceptin receptor. Thus, [Phe1psi (CH2-NH) Gly2]-nociceptin-(1-13)-NH2 appears to be an agonist rather than an antagonist of nociceptin (ORL1) receptor in rat PO/AH neurons. However, there was neither antagonism nor additive synergism when nociceptin and [Phe1psi (CH2-NH) Gly2]-nociceptin-(1-13)-NH2 were applied simultaneously at equimolar concentrations. The effect of nociceptin on tonic activity of rat PO/AH neurons was not blocked by selective mu-, kappa- and delta-opioid receptor antagonists (D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2 (CTOP), nor-binaltorphimine and naltrindol, respectively) at 10 times higher concentrations than nociceptin. These data suggest that the effect of nociceptin on tonic activity of PO/AH neurons is not due to an action on mu-, kappa-, or delta-opioid receptors but results from a specific effect on the ORL1-receptor.

Animals↗
PubMed1999

Nociceptin/orphanin FQ: effects on thermoregulation in rats.

Nociceptin/orphanin FQ is a 17 amino acid peptide which acts as a potent endogenous agonist of the opioid receptor-like 1 (ORL1) receptor. ORL1 receptor is a G protein-coupled unique member of the cloned opioid receptor family. We have investigated the effects of nociceptin (1, 10 and 100 nM) on the temperature sensitivity of neurons from the preoptic area of the anterior hypothalamus (PO/AH) in rat brain slices. The body temperature of male Wistar rats was measured after intrahypothalamic application of nociceptin (1 nM) via cannulas in the PO/AH. Low dose nociceptin (1 nM) significantly increased (p < 0.05) temperature sensitivity (TC) of warm-sensitive PO/AH neurons, while the high concentration (100 nM) decreased TC in both warm-sensitive and temperature-insensitive neurons. Similar agonistic activity was obtained after addition of [Phe1 psi (CH2-NH) Gly2]-nociceptin-(1-13)-NH2 (1, 10 and 100 nM), recently proposed to be a selective antagonist of the nociceptin receptor. Neither antagonism nor additive synergism were observed when nociceptin and [Phe1 psi (CH2-NH) Gly2]-nociceptin-(1-13)-NH2 were applied simultaneously in equimolar concentrations. The selective opioid OP3 receptor antagonist CTOP, the selective opioid OP2 receptor antagonist nor-binaltorphimine and selective opioid OP1 receptor antagonist naltrindol had no influence on the effects of nociceptin on temperature sensitivity in PO/AH neurons. In vivo experiments showed that nociceptin (1 nM; 1 microliter/rat) significantly decreased body temperature (p < 0.05) between 30 and 60 min after intrahypothalamic application. These data are in agreement with the hypothesis that the specific action of endogeous substances on body temperature appears to be closely related to a specific change in the temperature sensitivity of warm-sensitive PO/AH neurons.

Animals↗
PubMed1998

Effects of kappa and delta opioid agonists on activity and thermosensitivity of rat hypothalamic neurons.

Extracellular recordings were made from 161 warm-sensitive, six cold-sensitive and 153 temperature-insensitive neurons in slices of the preoptic area/anterior hypothalamus (PO/AH) of rats, to investigate the effects of the kappa-receptor opioid agonist dynorphin A1-17 and the delta-receptor opioid agonist DPDPE on neuronal response characteristics. While 61% of the neurons exhibited kappa-receptors, delta-receptors were only present in 37% of the neurons. No co-localization was observed between kappa- and delta-receptors, whereas mu-receptors could be co-localized with kappa- as well as delta-receptors. Antagonistic effects on tonic activity were induced by different concentrations of the kappa-agonist dynorphin A1-17. At 0.5 nM, the excitatory effect was predominant, while 50% of the neurons were already inhibited at 5 nM and inhibition was the major effect at 100 nM. A significant increase in temperature sensitivity was observed in warm-sensitive neurons during administration of 0.5 nM dynorphin A1-17; in contrast, the temperature sensitivity was significantly decreased at the high dose of 100 nM. In most of the neurons responding to the delta-receptor agonist DPDPE (0.5-100 nM) the firing rate was decreased. The temperature sensitivity was only affected in warm-sensitive neurons, and was increased in the majority of neurons at 0.5 and 5 nM, but predominantly decreased at higher concentrations. The effects of low concentrations of dynorphin A1-17 and DPDPE were prevented by pre- and co-perfusion of the appropriate antagonists. The present results suggest that changes of the temperature sensitivity of warm-sensitive PO/AH neurons are an important mechanism for the effect of low doses of opioids on body temperature.

Animals↗
PubMed1996

Neuronal basis for the hyperthermic effect of mu-opioid agonists in rats: decrease in temperature sensitivity of warm-sensitive hypothalamic neurons.

The effect of the selective mu-opioid receptor agonist Tyr-Pro-N-MePhe-D-NH2 (PL-017) on tonic activity and temperature sensitivity of neurons in the preoptic area/anterior hypothalamus (PO/AH) has been examined in rat brain slices using extracellular recordings. The tonic activity of both warm-sensitive and temperature-insensitive neurons was inhibited in a dose-dependent manner by superfusion with the mu-agonist (0.5-100 nM). The temperature sensitivity was selectively decreased in warm-sensitive neurons in concentrations up to 10 nM. Only in the high concentration of 100 nM did the mu-agonist reduce the temperature coefficient of both types of neurons. Pretreatment with equimolar concentrations of the mu-antagonist D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2 (CTOP) prevented the effects of the mu-agonist (0.5-10 nM) on tonic activity as well as temperature sensitivity. The results suggest that a specific change of the temperature sensitivity of PO/AH neurons is involved in the hyperthermia induced by mu-agonists in rats.

Animals↗
PubMed1988

Hyperthermia and antinociceptive activity of thyrotropin-releasing hormone and morphine following central administration in rats.

This is an assessment of thyrotropin-releasing hormone (TRH) and morphine effects on nociceptive activity and temperature reaction in male Wistar rats following introduction of the substances into the periaqueductal gray matter or preoptic anterior hypothalamic nuclei via before hand cannulation. Morphine (10 micrograms) had marked antinociceptive activity, as shown by the tail flick-test, hot plate-test and mechanical pressure according to Randall-Selitto. TRH (5 micrograms) showed antinociceptive activity upon introduction into the periaqueductal gray matter, better expressed in the mechanical pressure test. Morphine (10 micrograms) and TRH (5 micrograms) gave rise to a hyperthermic reaction. The antinociceptive activity of morphine reduced upon preliminary administration of TRH, while its hyperthermic effect remained unchanged. These data are in support of the hypothesis that TRH may act as a functional opiate antagonist in the central nervous system.

Analgesics↗