Biomedical subjects

J Kotlińska

Publications and source records attributed to J Kotlińska.

18 recordsLinked to original sources

PubMed2002

Orphanin FQ/nociceptin but not Ro 65-6570 inhibits the expression of cocaine-induced conditioned place preference.

The present study investigated the effect of orphanin FQ/nociceptin (OFQ/N), the endogenous ligand of the opioid receptor-like 1 (ORL-1) receptor on the expression of cocaine-induced conditioned place preference (CPP) in rats. To extend this study, the new non-peptidic compound Ro 65-6570 (8-acenaphthen-1-yl-1-phenyl-1,3,8-triaza-spiro[4,5]decan-4-one), with agonist activity at ORL-1 receptors, was examined. The influence of both compounds on cocaine-induced hyperactivity was also studied. Our experiments indicated that intracerebroventricular (i.c.v.) injection of OFQ/N, at doses of 10 and 20 microg/rat, significantly suppressed the expression of cocaine-induced place preference. Ro 65-6570 (3 and 6 mg/kg, i.p.) did not change the effect of cocaine, although its acute injection in control rats significantly increased the time spent in the drug-associated compartment of the CPP apparatus. The substances exhibited opposite effects on cocaine-induced hyperactivity (OFQ/N suppressed it but Ro 65-6570 increased it). Our results suggest that the effect of OFQ/N on the expression of cocaine-induced CPP may be a result of its influence on dopamine (DA) neurotransmission in mesolimbic structures. Ro 65-6570 does not share this effect with OFQ/N.

Animals↗

PubMed2001

Dynorphin A inhibits nociceptin-converting enzyme from the rat spinal cord.

Cysteine proteinase found in the spinal cord of rat, called nociceptin-converting enzyme (NCE), is competitively inhibited by dynorphin A and its fragment des-[Tyr(1)]-DYN A. This proteinase converts orphanin FQ/nociceptin (OFQ/N) to two major fragments: OFQ/N(1-11) and further OFQ/N(1-6) with analgesic properties. Dynorphin A at the concentration of 10 microM increases K(M) from 15.0 to 55.9 microM. The calculated K(i) for this interaction was estimated at 3.7 microM. This observation may suggest an interaction between opioid and nociceptive systems which may be affected by the balance between opioid and antiopioid systems. This balance between particular OFQ/N sequences that are derived from the same precursor and regulated by proteinases may play an important role in pain. Interestingly, dynorphin B does not reveal a similar action on the NCE.

Amino Acid Sequence↗

PubMed2001

C-Terminal glycine is crucial for hyperalgesic activity of nociceptin/orphanin FQ-(1-6).

A C-terminal analog of the hexapeptide orphanin FQ/nociceptin-(1-6), [Ala(6)]-orphanin FQ/nociceptin-(1-6), and a pentapeptide orphanin FQ/nociceptin-(1-5) were tested in vivo for their analgesic/hyperalgesic activity in the hot-plate test with rats. Replacement of the C-terminal glycine by L-alanine (Phe-Gly-Gly-Phe-Thr-Ala) in orphanin FQ/nociceptin-(1-6) abolished the hyperalgesic potency of native orphanin FQ/nociceptin-(1-6) (Phe-Gly-Gly-Phe-Thr-Gly), but analgesic activity was retained and was diminished by naloxone. Removal of the C-terminal amino acid (glycine or alanine) from orphanin FQ/nociceptin-(1-6) caused a significant loss of analgesic activity. It is anticipated that glycine plays a crucial role in the biphasic activity of orphanin FQ/nociceptin-(1-6). This may suggest the existence of a mechanism for terminating the biological action of orphanin FQ/nociceptin.

Amino Acid Sequence↗

PubMed2001

Attenuation of morphine dependence and withdrawal by glycine B site antagonists in rats.

Numerous data indicate that noncompetitive and competitive N-methyl-D-aspartate (NMDA) receptor antagonists inhibit the development of physical dependence on opioids when these substances are administered together, and NMDA receptor antagonists are used at lower range of doses. Higher doses of these antagonists can enhance some opioid-induced effects. The present study extends these findings to the effects of NMDA/glycine (glycine(B)) site antagonists. Wistar rats were rendered dependent on morphine by implantation of morphine pellets. Both of the glycine(B) site antagonists used, 7-chloro-4-hydroxy-3-(3-phenoxy)-phenyl-2(H)-quinolone (L-701,324; 2.5 and 5.0 mg/kg) and 5,7-dichlorokynurenic acid (5,7-DCKA; 25, 50, and 100 mg/kg), suppressed the expression of morphine withdrawal syndrome estimated as wet dog shakes. Furthermore, L-701,324 (2.5 and 5 mg/kg), given twice a day during the development of morphine dependence, attenuated the development of morphine dependence, and the results were comparable to those obtained after administration of noncompetitive NMDA receptor antagonist - MK801 (0.1 mg/kg). Our data suggest that glycine(B) site antagonists may attenuate wet dog shakes (withdrawal) and the development of dependence, both being induced by chronic morphine administration in rats.

Animals↗

PubMed2000

Orphanin FQ/nociceptin inhibits morphine withdrawal.

The influence of orphanin FQ/nociceptin (OFQ/N) on the morphine-withdrawal symptom was investigated. Withdrawal syndrome was induced in the morphine-dependent rats by an intraperitoneal (i.p.) injection of 2 mg/kg naloxone hydrochloride--an opioid receptors antagonist. Wet-dog shakes were used as a measure of the abstinence syndrome. Intraventricular injections of OFQ/N (5-20 microg/animal) caused significant inhibition of the withdrawal signs at doses between 15-20 microg, in the morphine-dependent rats. OFQ/N alone did not change behavior of the morphine-dependent animals. The obtained results indicate that OFQ/N can inhibit the morphine withdrawal symptoms induced by naloxone.

Animals↗

PubMed2000

Determination of nociceptin-orphanin FQ metabolites by capillary LC-MS.

Nociceptin-orphanin FQ (OFQ/N) is a newly discovered peptide involved in pain transmission. The method is described to identify metabolic pathway of this neuropeptide in the spinal cord of rats using capillary size-exclusion liquid chromatography coupled to electrospray ionization mass spectrometry. The applied technique is rapid and selective, and allows for simultaneous measurement and quantitation of several fragments in the incubation mixture.

Animals↗

PubMed1995

Influence of CGS 8216 on some acute effects of ethanol.

The central pharmacological effects of ethanol are well known and resemble those of the benzodiazepines (BZD). In addition BZD may interact with ethanol, resulting in enhanced cerebral depression. Ro 15-4513, BZD inverse agonist, potentially antagonizes a lot of effects of ethanol but not all. In our study, another BZD inverse agonist, CGS 8216, reverses the hypnotic effect of ethanol and hypoactivity in mice and rats. CGS 8216 increased also ethanol's locomotor stimulation in mice. This supports the hypothesis that some effects of ethanol are mediated by the GABA-BZD-chloride channel receptor complex. Our behavioural experiments described in this report suggest that CGS 8216, like Ro 15-4513, may act on the alpha-6 subunit of this receptor complex.

Animals↗

PubMed1987

Cross-tolerance between morphine and ethanol and their antinociceptive effects.

Morphinization of mice (37.5 mg morphine) and rats (75 mg) with subcutaneously implanted pellets has resulted in tolerance to the antinociceptive effect of morphine, measured in the tail-immersion test. All animals also developed cross-tolerance to the analgesic effects of ethanol (2.8 g/kg intraperitoneally for mice, per os for rats). These results suggest a commonality between morphine and ethanol antinociceptive action.

Analgesics↗

PubMed1987

Does the blockade of opioid receptors influence the development of ethanol dependence?

We have tested whether the opioid antagonists naloxone (2 mg/kg), naltrexone (2 mg/kg) and diprenorphine (0.2 mg/kg), and the agonist morphine (4-8 mg/kg) given subcutaneously (10 min before ethanol for 7 days) modify the ethanol withdrawal syndrome (audiogenic seizures) following chronic ethanol intoxication in rats. We found that naloxone, naltrexone and diprenorphine modified the ethanol withdrawal syndrome. These findings do not rule out the possibility of a biochemical link between the action of ethanol and opiates at the level of opioid receptors.

Alcoholism↗

PubMed1986

Audiogenic seizures during ethanol withdrawal can be blocked by a delta opioid agonist.

In rats the influence of the delta opioid agonists [Leu]enkephalin, [D-Ala2-D-Leu5]enkephalin, [D-Ala2]methionine enkephalinamide and synthetic analogue of [Met]enkephalin: Tyr-D-Ala-Gly-Phe-D-Leu-OMe on audiogenic seizures was tested during ethanol abstinence. All investigated drugs significantly inhibited this ethanol withdrawal symptom. The results are compatible with the hypothesis of opioid involvement in the ethanol abstinence syndrome.

Acoustic Stimulation↗

PubMedDate not supplied

Blockade of the acquisition of ethanol-induced conditioned place preference by N-methyl-D-aspartate receptor antagonists.

We have examined the influence of two different N-methyl-D-aspartate (NMDA) receptor antagonists on acquisition of the reinforcing properties of ethanol measured in the conditioned place preference (CPP) paradigm in rats. After receiving 15 daily injections of ethanol (0.5 g/kg, i.p.) before the conditioning trials, rats acquired the preference to the compartment paired with ethanol injections during conditioning. Both dizocilpine (0.1 mg/kg, i.p.), a non-competitive antagonist of the NMDA receptor, and L-701,324 (5 mg/kg, per os), an antagonist acting at the strychnine-insensitive glycine site of NMDA receptor complex, when co-administered repeatedly with ethanol, prevented the acquisition of ethanol-induced CPP. Dizocilpine alone provoked the development of CPP, having some intrinsic rewarding properties. In contrast, L-701,324 alone did not affect the CPP. These results suggest that the rewarding properties of ethanol could be, at least in part, due to its action at the NMDA receptor complex. Additionally, we can speculate that NMDA receptor antagonists can be useful in the treatment of ethanol dependence. Glycine receptor antagonists having no abuse potential might have advantages in terms of safety compared to non-competitive NMDA receptor antagonists.

Animals↗

PubMedDate not supplied

Effects of the NMDA/glycine receptor antagonist, L-701,324, on morphine- and cocaine-induced place preference.

Effects of the novel NMDA/glycine receptor antagonist, L-701,324, on morphine- and cocaine-induced conditioned place preference (CPP) were examined in male Wistar rats. After determination of initial preference, animals were conditioned with morphine (5 mg/kg, i.p.) or cocaine (5 mg/kg, i.p.) for 3 conditioning trials, alone or in combination of these drugs with L-701,324 (2.5 mg/kg and 5 mg/kg, p.o.). L-701,324 prevented acquisition of the place preference produced by morphine and cocaine. Administration of L-701,324 on the test day attenuated the expression of morphine-induced CPP, whereas it had no effect on cocaine CPP. When L-701,324 was given alone it did not affect dependent variables (i.e. time spent in non-preferred compartment) suggesting that L-701,324 did not display any reinforcing properties by itself. Our current data suggest that glycine site on the NMDA receptor complex may be involved in the mediation of the rewarding effects of drugs of abuse.

Analgesics, Opioid↗

PubMedDate not supplied

Memantine and ACPC affect conditioned place preference induced by cocaine in rats.

The influence of uncompetitive NMDA receptor antagonist, 1-amino-3,5--dimethyl-adamantane (memantine) and partial glycineB site agonist, 1-amino-cyclopropanecarboxylic acid (ACPC) on cocaine-induced conditioned place preference (CPP) were examined in male Wistar rats. After determination of initial preference, animals were conditioned with cocaine (5 mg/kg, ip) for 3 conditioning trials, alone or in combination with memantine (7.5 mg/kg, ip) or ACPC (50.0 mg/kg, ip). Memantine prevented acquisition and expression of the place preference produced by cocaine, while ACPC prevented only acquisition effect. Neither of the NMDA antagonists displayed any reinforcing properties by itself. Our current data suggest that the NMDA receptor complex may be involved in the rewarding effect of cocaine.

Amino Acids, Cyclic↗

PubMedDate not supplied

NMDA antagonists inhibit the development of ethanol dependence in rats.

The influence of non-competitive NMDA receptor antagonist, 1-amino-3,5-dimethyl-adamantane (memantine), and glycineB site antagonist, 7-chloro-4-hydroxy-3-(3-phenoxy)phenyl-2(1H)-quinolone (L-701,324), on the development of ethanol dependence was investigated in Wistar rats. The development of ethanol dependence was induced by intragastric administration of 20% w/v ethanol, three times a day at increasing doses. The results were quantified using withdrawal audiogenic seizures, 12 h after the last ethanol administration. Memantine (3.75 or 7.5 mg/kg) and L-701,324 (2.5 or 5 mg/kg), given before ethanol administration, prevented the development of ethanol dependence. Our results support the data that NMDA receptors are involved in the development of ethanol dependence.

2-Amino-5-phosphonovalerate↗

PubMedDate not supplied

Are glycineB sites involved in the development of morphine tolerance?

Numerous data have indicated that competitive and non-competitive N-methyl-D-aspartate (NMDA) receptor antagonists attenuate the development of tolerance to the analgesic effect of morphine. This study extends these findings on the effects of glycine(B) site antagonist, L-701.324. Tolerance to the analgesic effect of morphine was measured in hot-plate test in Wistar rats. For 9 days, animals were first injected with vehicle or glycine(B) receptor antagonist, L-701.324 (2.5 and 5 mg/kg, po). The non-competitive NMDA receptor antagonist, MK-801 (0.05 or 0.1 mg/kg, ip) was used as a reference compound. The injection of L-701.324, MK-801 or saline was followed, 20 min later, by the injection of morphine (10 mg/kg, sc). Hot-plate latencies were determined 20 min after the second injection on odd-numbered days. The results indicated that chronic administration of glycine(B) site antagonist, L-701.324 decreased the analgesic effect of morphine and they may suggest that this substance at both used doses increased the development of morphine tolerance, whereas non-competitive NMDA antagonist, MK-801 at the dose of 0.1 mg/kg potentiated the analgesic effect of morphine and attenuated the development of morphine tolerance.

Administration, Oral↗

PubMedDate not supplied

The lack of effect of opioid agonists and antagonists on some acute effects of ethanol.

We studied the ability of opioid antagonists: naloxone, naltrexone and diprenorphine and an opioid agonist morphine to influence the effects of ethanol on hypothermia, sleeping time and impairment of aerial righting reflex. Naltrexone (2-16 mg/kg) and naloxone (2-16 mg/kg) were not able to attenuate effects of ethanol, while diprenorphine decreased ethanol sleeping time (4 microgram/kg) and antagonized the ethanol hypothermia (8 microgram/kg). Naltrexone in a dose of 8 mg/kg sc antagonized the ethanol impairment of aerial righting reflex. The present behavioral studies did not provide any evidence for the participation of the opioid system in the mediation of acute ethanol effects in rats.

Animals↗

PubMedDate not supplied

Involvement of opioid and other systems in ethanol abstinence audiogenic seizures in the rat?

The action of opiate receptor agonists: (D-Ala2)-methionine enkephalinamide (D-MEA), morphine, heroin, etorphine, and antagonists: naloxone and diprenorphine on audiogenic seizures was tested during ethanol abstinence. The action of diazepam and clonidine was also tested Morphine (5 and 20 mg/kg), but not heroin and etorphine, given intraperitoneally inhibited the seizures, similarly as intraventricularly administered D-MEA did. However, morphine given by this route was ineffective. Diazepam and clonidine inhibited audiogenic seizures: the action of clonidine was counteracted by yohimbine, but not by prazosin. The results may be considered as supporting the hypothesis on the participation of opioid system in ethanol abstinence. However, the participation of gabergic and noradrenergic systems cannot be ruled out: these systems may possibly interact with the opioid system in evoking the symptoms of ethanol abstinence.

Acoustic Stimulation↗

PubMedDate not supplied

Ethanol-opioid interaction in mice.

The influence of opiate receptor antagonists: naloxone, naltrexone and diprenorphine, and of an agonist: morphine on ethanol-induced sleep, hypothermia and motor coordination impairment was investigated. Naloxone and naltrexone evidently antagonized the sleep and hypothermia, and improved the motor coordination impaired by ethanol. Naltrexone was the most, and diprenorphine the least potent ethanol antagonist. Morphine potentiated only ethanol-induced sleep, and this effect was opiate dependent (reversible by naloxone). The present results may partially support the hypothesis about participation of opioid system in ethanol action. However, ethanol effects were affected only by high doses of opiate antagonists, exceeding by far the doses antagonizing the morphine effects. Therefore the participation of additional, unspecific mechanisms, in addition to an opiate-mediated one, cannot be excluded.

Animals↗