Rapid method for obtaining high-quality chromosome banding in the study of hematopoietic neoplasia

The antiemetic effects of six serotonergic 5-HT1A-receptor agonists, 8-hydroxy-2-(di-n-propylamino)tetrarin (8-OH-DPAT), 4-(4-[4-(2-pyrimidinyl)piperazin-1-yl]butyl)-2,3,4,5- tetrahydro-1,4-benzoxazepine-3,5-dione (SUN8399), buspirone, gepirone, ipsapirone and tandospirone, against motion sickness were investigated in Suncus murinus. Subcutaneous injection of all six agonists completely and dose-dependently suppressed motion-induced emesis. Pretreatment with 8-OH-DPAT or SUN8399 dose-dependently inhibited emesis elicited by nicotine (4.0 mg/kg, s.c.), veratrine (0.7 mg/kg, s.c.), cisplatin (20 mg/kg, i.p.) and copper sulfate (40 mg/kg, p.o.). These results suggest that serotonergic 5-HT1A-receptor agonists are effective as anti-motion sickness drugs, and these drugs may block a common mechanism(s) for the emetic reflex of the suncus because the antiemetic effects of the 5-HT1A-receptor agonists were exerted irrespective of the stimulus.     

Mycotic sinusitis

Previous drug discrimination studies have elucidated the importance of gamma-aminobutyric acidA (GABAA), N-methyl-D-aspartate (NMDA) glutamate, and serotonin (5-HT) receptor systems in mediating the discriminative stimulus effects of ethanol. The present study used a three-choice operant drug discrimination procedure in an attempt to determine if salient GABAergic effects could be separated from other stimulus effects of 2.0 g/kg ethanol. Adult male Long-Evans rats (n = 7) were trained to discriminate pentobarbital (10.0 mg/kg; intragastrically (i.g.) from ethanol (2.0 g/kg; i.g.) from water (4.7 ml; i.g.) using food reinforcement. Stimulus substitution tests were conducted following the administration of allopregnanolone (1.0-17.0 mg/kg; intraperitoneally (i.p.)), diazepam (0.1-7.3 mg/kg; i.p.), midazolam (0.0056-17.0 mg/kg; i.p.), dizocilpine (0.01-0.56 mg/kg; i.p.), phencyclidine (1.0-5.6 mg/kg; i.p.), CGS 12066B (3-30 mg/kg; i.p.), RU 24969 (0.1-5.6 mg/kg; i.p.) and morphine (1 or 3.0 mg/kg; i.p.). Within the group, allopregnanolone and midazolam completely substituted (> 80%), and diazepam partly substituted (67%) for the discriminative stimulus effects of pentobarbital. Dizocilpine and phencyclidine partly substituted (58 and 57%, respectively) for ethanol without substantial pentobarbital-appropriate responding. RU 24969, CGS 12066B and morphine did not result in complete substitution for either ethanol or pentobarbital, although RU 24969 resulted in partial (68%) pentobarbital substitution. The ability to train the present three-choice discrimination in rats indicates that the discriminative stimulus effects of 10.0 mg/kg pentobarbital were separable from those of 2.0 g/kg ethanol. The results suggest that the pharmacological effects of ethanol, which can control behavior, may seemingly be modified by training conditions (two-versus three-choice discrimination procedures), to the extent that a receptor system prominently linked to the behavioral activity of ethanol (i.e. GABAA) appears no longer to be involved in the interoceptive effects of the drug.     

Pharmacological analysis of the heterogeneous discriminative stimulus effects of ethanol in rats using a three-choice ethanol-dizocilpine-water discrimination

The present study used a three-choice operant drug discrimination procedure to determine if NMDA-mediated discriminative stimulus effects could be separated from other stimulus effects of 2.0 g/kg ethanol. Adult male Long-Evans rats (n = 7) were trained to discriminate dizocilpine (0.17 mg/kg; i.g.) from ethanol (2.0 g/kg; i.g.) from water (4.7 ml; i.g.) using food reinforcement. Substitution tests were conducted following administration of the GABA(A) positive modulators allopregnanolone (5.6-30.0 mg/kg; i.p.), diazepam (0.3-10.0 mg/kg; i.p.) and pentobarbital (1.0-21.0 mg/kg; i.p.), the non-competitive NMDA antagonist phencyclidine (0.3-10.0 mg/kg; i.p.), the 5-HT1 agonists TFMPP (0.3-5.6 mg/kg; i.p.) and RU 24969 (0.3-3.0 mg/kg; i.p.), and isopropanol (0.10-1.25 g/kg; i.p.). Allopregnanolone, diazepam and pentobarbital substituted completely (>80%) for ethanol. Isopropanol partially (77%) substituted for ethanol. Phencyclidine substituted completely for dizocilpine. RU 24969 and TFMPP did not completely substitute for either training drug, although RU 24969 partially (62%) substituted for ethanol. Successful training of this three-choice discrimination indicates that the discriminative stimulus effects of 0.17 mg/kg dizocilpine were separable from those of 2.0 g/kg ethanol. The finding that attenuation of NMDA-mediated effects of ethanol occurred without altering significantly GABA(A)- and 5-HT1-mediated effects suggests that the NMDA component may be independent of other discriminative stimulus effects of 2.0 g/kg ethanol.     

The aminoacceptor stem of the yeast tRNA(Lys) contains determinants of mitochondrial import selectivity

The effect of quinine, a cinchona alkaloid, was studied on gastrointestinal transit in mice. Intraperitoneal (i.p.) administration of quinine inhibited the intestinal propulsion of a charcoal suspension at a dose of 100 mg/kg, comparing favorably with 5 mg/kg morphine. In an attempt to probe into the mechanism underlying this inhibition, a possible modulation by minoxidil (1 mg/kg, p.o.) and glibenclamide (1 mg/kg, p.o.), the drugs that, respectively, open and close ATP-sensitive K+ channels was tested on gastrointestinal transit in animals treated or not with quinine or morphine. While minoxidil produced no significant change of normal transit, glibenclamide significantly increased it. However, both drugs blocked the quinine-induced reduction in gastrointestinal transit. In contrast, the inhibitory effect of morphine on gastrointestinal transit was not modified by either drug. The effects of quinine as well as of morphine on gastrointestinal transit were significantly antagonized by naloxone (2 mg/kg, s.c.), a mu-opioid receptor antagonist but not by yohimbine (1 mg/kg, i.p.), an alpha2-adrenoceptor antagonist. Furthermore, quinine at a lower dose (25 mg/kg) that showed no per se effect on gastrointestinal transit, significantly potentiated the response to 2.5 mg/kg morphine. Although the role of ATP-sensitive K+ channels in the action of quinine and morphine was not clarified by the present results, a possible involvement of endogenous opioid(s) in the quinine-induced inhibition of gastrointestinal transit can be suggested.     

Effect of 7-nitroindazole on tolerance to morphine, U-50,488H and [D-Pen2, D-Pen5] enkephalin in mice

The effects of 7-nitroindazole (7-NI), an inhibitor of the neuronal nitric oxide synthase (nNOS) which does not increase blood pressure, on tolerance to the antinociceptive activity of mu-(morphine), kappa-(U-50,488H) and delta-([D-Pen2, D-Pen5]enkephalin, DPDPE) opioid receptor agonists were determined in mice. Male Swiss-Webster mice were made tolerant by twice daily injections of morphine (20 mg/kg, s.c.), U-50,488H (25 mg/kg, i.p.) or DPDPE (20 micrograms/mouse, i.c.v.) for 4 days. When tested on day 5, tolerance to their antinociceptive activity was evidenced by decreased response in chronic drug treated mice in comparison to vehicle-injected mice. Concurrent administration of 7-NI (20, 40 or 80 mg/kg, i.p.) with DPDPE did not modify the development of tolerance to the antinociceptive action of DPDPE. However, 7-NI (40 or 80 mg/kg, i.p.) inhibited the development of tolerance to the antinociceptive activity of morphine and U-50,488H but the lower dose of 7-NI (20 mg/kg, i.p.) was not effective. Chronic administration of 7-NI by itself did not modify the acute response to morphine, U-50,488H or DPDPE. It is concluded that a specific inhibitor of nNOS can inhibit tolerance to the antinociceptive activity of mu- and kappa- but not of delta-opioid receptor agonists in mice.     

Effects of amphetamine, morphine and dizocilpine (MK-801) on spontaneous alternation in the 8-arm radial maze

The induction of psychomotor activation, behavioural sensitization and of perseverative behaviours, resulting in reduced behavioural variability, have been proposed to be common properties of drugs of abuse. The present investigation tested whether these drug effects could be measured using spontaneous alternation in an 8-arm radial maze. Behavioural effects of repeated treatment with amphetamine (2 and 4 mg/kg, i.p.), morphine (1.25 and 10 mg/kg, i.p.) and the non-competitive NMDA receptor antagonist, MK-801 (0.1 and 0.2 mg/kg, i.p.), on spontaneous alternation were evaluated in this paradigm. All drugs induced psychomotor activation. Sensitized as well as reduced locomotor activity could be observed after repeated treatment depending on drug and dose. Analysis of the sequences of arm entries revealed that all drugs induced perseverative locomotor patterns, but the pattern induced by amphetamine and morphine differed qualitatively from the pattern induced by MK-801.     

An adenosine kinase inhibitor attenuates tactile allodynia in a rat model of diabetic neuropathic pain

The present study was conducted to characterize the development of tactile allodynia in the streptozotocin-induced rat model of diabetes, and to evaluate the antinociceptive effects of systemically administered morphine and the adenosine kinase inhibitor, 5'-deoxy-5-iodotubercidin (5'd-5IT) in this model. Rats were injected with 75 mg/kg streptozotocin (i.p.), and blood glucose levels were determined 3-4 weeks later. Diabetic (blood glucose levels > or = 250 mg/dl) and vehicle-injected rats were examined weekly for the development of tactile allodynia by measuring the threshold for hind paw withdrawal using von Frey hairs. Withdrawal thresholds were reduced to 6.8+/-0.6 g (mean+/-S.E.M.) in approximately one-third of streptozotocin-treated rats 7 weeks after streptozotocin treatment as compared to control thresholds (13.2+/-0.1 g), and this allodynia persisted for at least an additional 7 weeks. In additional experiments, morphine sulfate (5-21 micromol/kg, i.p.) produced dose-dependent antinociceptive effects on tactile allodynia for up to 2 h post-dosing. The adenosine kinase inhibitor, 5'd-5IT (2.5 and 5 micromol/kg, i.p.) also dose-dependently attenuated tactile allodynia. Pretreatment with the opioid receptor antagonist, naloxone (27 micromol/kg, i.p.) or the non-selective adenosine receptor antagonist, theophylline (111 micromol/kg, i.p.) significantly diminished the anti-allodynic effects of morphine and 5'd-5IT, respectively. The present study demonstrates that the potent and selective adenosine kinase inhibitor, 5'd-5IT, is equally effective as morphine in blocking tactile allodynia in this model.     

Effects of mu and delta opioid agonists and antagonists on affective vocal and reflexive pain responses during social stress in rats

The present experiments evaluated the influence of intraventricular mu and delta opioid receptors on affective vocal and reflexive responses to aversive stimuli in socially inexperienced, as well as defensive and submissive responses in defeated, adult male Long-Evans rats. Defeat stress consisted of: (1) an aggressive confrontation in which the experimental intruder rat exhibited escape, defensive and submissive behaviors [i.e., upright, supine postures and ultrasonic vocalizations (USV)], and subsequently, (2) protection from the resident stimulus rat with a wire mesh screen for 10-20 min. Defeat stress was immediately followed by an experimental session with tactile startle (20 psi). The mu opioid receptor agonists morphine (0.1-0.6 microg i.c.v.) and [D-Ala2-N-Me-Phe4-Gly5-ol]-enkephalin (DAMGO; 0.01-0.3 microg i.c.v.), and the delta opioid receptor agonist [D-Pen2,5]-enkephalin (DPDPE; 10-100 microg i.c.v.) dose-dependently decreased startle-induced USV and increased tail-flick latencies in socially inexperienced and defeated rats. Of greater interest, morphine, DAMGO and DPDPE increased the occurrence of the submissive crouch posture, and defeated rats were more sensitive than socially inexperienced rats to the startle-induced USV-suppressive and antinociceptive effects of morphine and DPDPE. The antinociceptive effects of DAMGO were likewise obtained at lower doses in defeated rats. Finally, the USV-suppressive effects of morphine and DAMGO were reversed with the mu receptor antagonist naltrexone (0.1 mg/kg i.p.), but the USV-suppressive effects produced by DPDPE were not reversed with the delta receptor antagonist naltrindole (1 mg/kg i.p.). These results confirm mu, but not delta opioid receptor activation as significant in affective vocal, passive-submissive behavior, as well as reflexive antinociception. Furthermore, similar to previous studies with restraint and electric shock stress, the facilitation of mu opioid effects on vocal responses and antinociception is consistent with the proposal that defeat stress activated endogenous opioid mechanisms.     

Selenium and iodine deficiencies and selenoprotein function

The present study was designed to evaluate the roles of 5-HT2 and 5-HT3 receptors in the mouse forced swimming test, by using selective agonists and antagonists of 5-HT(2A/C) and 5-HT3 receptor sites. Agonists/antagonists and antidepressants were administered 45 min and 30 min, respectively, prior to testing. Pretreatment with (+/-)-2,5-dimethoxy-4-iodoamphetamine (DOI) (4 mg/kg, i.p.) or 2-methyl-5-HT (4 mg/kg, i.p.) had no effect on the anti-immobility effects of any antidepressant tested. Prior administration of ritanserin (4 mg/kg, i.p.) or ketanserin (8 mg/kg, i.p.), on the other hand, potentiated the effects of sub-active doses of imipramine (8 mg/kg, i.p.) and desipramine (16 mg/kg, i.p.) but not of maprotiline (8 mg/kg, i.p.), fluoxetine (16 mg/kg, i.p.), citalopram (16 mg/kg, i.p.) or fluvoxamine (8 mg/kg, i.p.). Pretreatment with ondansetron (1 X 10(-5) mg/kg, i.p.) enhanced the antidepressant-like effects of sub-active doses of the selective serotonin reuptake inhibitors. The results of the present study suggested that, in the forced swimming test, the selective serotonin reuptake inhibitors act partially through 5-HT3 receptor sites, whereas the tricyclic antidepressants exert effects at 5-HT(2A/C) receptor sites. Anti-immobility effects of the selective noradrenaline reuptake inhibitor, maprotiline, do not seem to be mediated by 5-HT(2A/C) or 5-HT3 receptor function.     

Prior morphine exposure enhances ibogaine antagonism of morphine-induced dopamine release in rats

The present study examines the effect of prior morphine exposure on ibogaine antagonism of morphine-induced dopamine release. Female Sprague-Dawley rats were pretreated once a day for 2 days with morphine (20 mg/kg, i.p.) or saline and given a low dose of ibogaine (10 mg/kg, i.p.) or saline 5 hr after the last morphine or saline injection. Nineteen hours later, rats (awake and freely moving) were challenged with morphine (5 mg/kg, i.p.), and dopamine and its metabolites were monitored in the striatum and nucleus accumbens using in vivo microdialysis. Neither saline pretreatment, morphine pretreatment, nor ibogaine alone altered morphine-induced increases in extracellular dopamine and dopamine metabolites in either structure. However, when morphine pretreatment was combined with ibogaine, the morphine-induced elevation of dopamine, but not of metabolites, was completely blocked. These data suggest that prior morphine exposure enhances an opioid antagonist action of ibogaine on dopaminergic systems and that prior drug exposure may be a clinically significant determinant of ibogaine efficacy and/or potency in the treatment of opioid addiction.     

The effects of morphine, nicotine and epibatidine on lymphocyte activity and hypothalamic-pituitary-adrenal axis responses

Acute administration of morphine alters various neuroendocrine and immune parameters via opioid receptors located within the central nervous system. Similar effects have been reported after systemic nicotine treatment. To examine the possible relationship between opioid and nicotinic receptor activation on the immune system, we compared the effects of morphine with both nicotine and the highly selective nicotinic agonist, epibatidine. Male Sprague-Dawley rats were treated with either morphine (10 mg/kg, s.c.), nicotine (2.85 mg/kg, s.c. = 1 mg/kg freebase), or epibatidine (5 microg/kg, s.c.) and sacrificed 2 hours later. Each drug increased plasma corticosterone levels and decreased the magnitude of the peripheral blood lymphocyte proliferation response to the T cell mitogen concanavalin A. None of the treatments had a significant effect on splenic or thymic lymphocyte responses. The effects of nicotine treatment were dose-dependent. Pretreatment with the quaternary ganglionic antagonist chlorisondamine (0.5 mg/kg, i.p.), completely blocked the effect of epibatidine on blood lymphocytes without altering the elevation of corticosterone levels. Although naltrexone (10 mg/kg, s.c.) blocked all effects of morphine, the effects of epibatidine were not blocked by the opioid receptor antagonist. Furthermore, in contrast to morphine (), central injection of neither nicotine (30 or 240 nmol) nor epibatidine (5, 50, or 500 ng) altered blood lymphocyte responses. These results suggest that, like morphine, nicotinic agonists decrease blood lymphocyte proliferation responses, apparently independent of elevated corticosterone. However, unlike morphine, nicotinic agonists appear to act predominantly at peripheral receptors, suggesting that nicotinic receptors are downstream of opioid receptors in a centrally mediated opioid-induced immunomodulatory pathway.     

Comparison of the stimulus properties of ethanol and the Ca2+ channel antagonist nimodipine in rats

A variety of L-type Ca2+ channel antagonists, including the dihydropyridine derivative nimodipine, have been shown to be effective in reducing ethanol intake and preference in animal models of alcoholism. The behavioral mechanism involved in the anti-alcohol effects of nimodipine are, however, not clear yet. The aim of the present study was to investigate the possibility that the effects of nimodipine on ethanol intake are based on stimulus substitution. Therefore, rats were trained to discriminate ethanol (12.5% w/v, 1000 mg/kg i.p.) from saline in a two-lever food-reinforced drug discrimination procedure (dose range of ethanol tested: 125-1000 mg/kg i.p., ED50 value: 488 mg/kg). In cross-generalization tests with nimodipine (0.15-15 mg/kg i.p.), stimulus substitution was not noted. In addition, a cross-familiarization conditioned taste aversion paradigm was utilized. In rats, 1000 mg/kg i.p. ethanol was used as the reference drug producing a conditioned taste aversion. Effects of preexposure to ethanol (500-1500 mg/kg i.p.) and nimodipine (7.5-30 mg/kg i.p.) on the magnitude of the ethanol-induced conditioned taste aversion were investigated as an index for stimulus similarity between preexposure and reference drug. Preexposure to both ethanol and nimodipine prevented the development of a conditioned taste aversion. Contrary to the drug discrimination results, these latter findings suggest that there may be similarities between the stimulus properties of nimodipine and ethanol. Moreover, the apparent discrepancy between the results obtained in drug discrimination and cross-familiarization conditioned taste aversion suggests that different stimulus properties of ethanol control behavior in both procedures. The finding that, under particular conditions, ethanol and nimodipine appear to share common stimulus properties needs to be further evaluated, as this may be related to the reported anti-alcohol effects of nimodipine and other Ca2+ channel antagonists.     

Evidence for a role of N-methyl-D-aspartate receptors in L-arginine-induced attenuation of morphine antinociception

Twice daily injections of L-arginine (50, 100 or 200 mg/kg, i.p.) for 4 days dose-dependently, decreased morphine antinociception in male Swiss-Webster mice as measured by the tail-flick test. To determine the possible role of N-methyl-D-aspartate (NMDA) receptor in the action of L-arginine, the effects of MK-801, a noncompetitive antagonist of the NMDA receptor and of LY 235959, a competitive antagonist of the NMDA receptor on L-arginine-induced attenuation of morphine antinociception were determined. MK-801 (0.01-0.10 mg/kg, i.p.) or LY 235959 (1.0-4.0 mg/kg, i.p.) given 10 min before each injection of L-arginine (200 mg/kg, i.p.) reversed the action of the letter in a dose-dependent manner on morphine antinociception. It is concluded that NMDA receptors are involved in the action of L-arginine in attenuating morphine antinociception.     

In vivo functional interaction between phencyclidine binding sites and sigma receptors to produce head-weaving behavior in rats

To investigate the in vivo functional interaction between phencyclidine (1-(1-phenylcyclohexyl)piperidine; PCP) binding sites and sigma receptors, we examined the effects of sigma receptor ligands on stereotyped head-weaving behavior induced by PCP, a putative PCP/sigma receptor ligand, and (+)-5-methyl-10,11-dihydroxy-5H-dibenzo(a,d)cyclo-hepten-5,10-imin e ((+)-MK-801; dizocilpine), a selective PCP binding site ligand, in rats. PCP (7.5 mg/kg, i.p.)-induced head-weaving behavior was inhibited by both N,N-dipropyl-2-[4-methoxy-3-(2-phenylethoxy)-phenyl]-ethylamine (NE-100; 0.03-1.0 mg/kg, p.o.), a selective sigma1 receptor ligand, and alpha-(4-fluorophenyl)-4-(5-fluoro-2-pyrimidinyl)-1-piperidine butanol (BMY-14802; 3 and 10 mg/kg, p.o.), a prototype sigma receptor ligand, in a dose-dependent manner, whereas NE-100 (0.1-1.0 mg/kg, p.o.) and BMY-14802 (3 and 10 mg/kg, p.o.) did not inhibit dizocilpine (0.25 mg/kg, s.c.)-induced head-weaving behavior. These results suggest that NE-100 and BMY-14802 act via sigma receptors. Dizocilpine-induced head-weaving behavior was potentiated by 1,3-di-o-tolyl-guanidine (DTG; 0.03-0.3 microg/kg, i.v.) and (+)-3-(3-hydroxyphenyl)-N-(1-propyl)piperidine ((+)-3-PPP; 3 and 6 mg/kg, i.p.), sigma1/sigma2 receptor ligands, as well as by (+)-N-allyl-normetazocine ((+)-SKF-10,047: 8 mg/kg, i.p.), a sigma1 receptor ligand, while DTG (0.3 microg/kg, i.v.), (+)-3-PPP (6 mg/kg, i.p.) and (+)-SKF-10,047 (8 mg/kg, i.p.) did not induce this behavior. Potentiation of dizocilpine-induced head-weaving behavior by DTG (0.3 microg/kg, i.v.), (+)-3-PPP (6 mg/kg, i.p.) and (+)-SKF-10,047 (8 mg/kg, i.p.) was completely blocked by NE-100 (0.1 mg/kg, p.o.) and BMY-14802 (10 mg/kg, p.o.). These results suggest that PCP binding sites and sigma receptors are involved in PCP-induced head weaving behavior, and that sigma1 receptors play an important role in modulation of the head-weaving behavior.     

The role of endogenous nitric oxide in the gastroprotective action of morphine

Morphine in a dose of 1 mg/kg s.c. decreased mucosal lesions induced by 100% ethanol or acidified aspirin by 79% and 85%, respectively, in rats. When the animals were pretreated with NG-nitro-L-arginine (40 mg/kg i.v.), the mucosal lesions were aggravated in both tests and the gastroprotective action of morphine decreased to 17% and 20%, respectively. This decrease in morphine protection was antagonized by L-arginine but not by D-arginine in the case of ethanol-induced lesions; however, L-arginine failed to restore the gastroprotective effect of morphine when the mucosal damage was induced by acidified aspirin. The protective action of either prostaglandin E2 (0.1 mg/kg orally) or cysteamine (50 mg/kg orally) was not influenced by NG-nitro-L-arginine (L-NNA). When L-NNA was given simultaneously with either indomethacin (10 mg/kg p.o.) or N-ethyl-maleimide (50 mg/kg s.c.), compounds which also reduced the gastroprotective action of morphine, almost complete inhibition of the gastroprotective action of morphine against 100% ethanol-induced lesions was observed as a result of the addition of the inhibitory activities of the latter substances. These results suggest that: (1) Endogenous nitric oxide is likely to be involved in the gastroprotective action of morphine. (2) The protective action of nitric oxide is independent of both mucosal prostaglandins and sulfhydryls.     

Action of prostanoids on the emetic reflex of Suncus murinus (the house musk shrew)

Several prostanoids were investigated for a potential to induce emesis in Suncus murinus. The TP receptor agonist 11alpha,9alpha-epoxymethano-15S-hydroxyprosta-5Z,13E-dienoic acid (U46619) induced emesis at doses as low as 3 microg/kg, i.p. but the DP receptor agonist 5-(6-Carboxyhexyl)-1-(3-cyclohexyl-3-hydroxypropyl) hydantoin (BW245C) was approximately 1000 times less potent. The emetic action of U46619 (300 microg/kg, i.p.) was antagonized significantly by the TP receptor antagonist, vapiprost (P<0.05). EP (prostaglandin E(2), 17-phenyl-omega-trinor prostaglandin E(2), misoprostol and sulprostone), FP (prostaglandin F(2alpha) and fluprostenol) and IP (iloprost and cicaprost) receptor agonists failed to induce consistent emesis at doses up to 300-1000 microg/kg, i.p. Fluprostenol reduced nicotine (5 mg/kg, s.c.)-but not copper sulphate (120 mg/kg, intragastric)-induced emesis; the other inconsistently emetic prostanoids were inactive to modify drug-induced emesis. The results indicate an involvement of TP and possibly DP and FP receptors in the emetic reflex of S. murinus.     

Repeated treatment with high doses of morphine produces comparable tolerance to low- and high-dose discriminative stimulus effects of morphine.

Morphine tolerance was studied in 9 pigeons (Columba livia, N?=?9) trained to discriminate among a low dose of morphine (1.8 mg/kg), a high dose of morphine (10 mg/kg), and saline. Doses of morphine required for low-dose or high-dose stimulus effects were determined before, during, and after a 4-week treatment period, during which training was suspended. Treatment with 56 mg/kg, but not 10 mg/kg, morphine, b.i.d., increased the doses required for either low-dose or high-dose stimulus effects by approximately 10-fold. Both treatments increased doses required for rate suppression. Sensitivity recovered after a week of saline treatment. Acute treatment with 56 mg/kg morphine did not change sensitivity. These results suggest that chronic morphine treatment can produce surmountable, reversible tolerance to morphine acting as a discriminative stimulus, without disrupting a discrimination between low-dose and high-dose stimulus effects. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Abdominal non-Hodgkin''s lymphoma in childhood

Effect of 3, 4-dihydroxyphenylserine (DOPS), a norepinephrine precurosr, on harmaline tremor was investigated in mice to elucidate the role of norepinephrine in the genesis of tremor. 1) Spontaneous motor activity was inhibited by L-threo-DOPS (200 mg/kg i.p.). 2) Tremor induced by harmaline (5 and 7 mg/kg i.p.) was enhanced by alpha-methyl-p-tyrosone (200 mg/kg i.p.). 3) The development and duration of tremor induced by harmaline (10 mg/kg i.p.) were inhibited significantly in a dose dependent manner by L-threo-DOPS (50, 70, 100, 150 and 200 mg/kg i.p.), but neither by D-threo-DOPS (200 mg/kg i.p.) nor DL-erythro-DOPS (200 mg/kg i.p.). 4) L-threo-DOPS (200 mg/kg i.-.) had no effect on the development of tremor induced by tremorine (5 and 10 mg/kg i.p.), while lacrimation and diarrhea caused by tremorine was markedly inhibited. 5) Administration of harmaline (10 mg/kg i.p.) produced an increase in brain 5-hydroxytryptamine content but not in that of norepinephrine. Administration of L-threo-DOPS (100 mg/kg i.p.) increased the norepinephrine content but not the 5-hydroxytryptamine content in the brain. Inhibition of harmaline tremor induced by L-threo-DOPS is attributed to the L-norepinephrine converted from L-threo-DOPS and the involvement of a noradrenergic mechanism in harmaline tremor has to be considered.     

Motor effects of lamotrigine in naive and dopamine-depleted mice

Lamotrigine (3,5-diamino-6-[2,3-dichlorphenyl]-1,2,4-triazine) has been hypothesised to possess antiparkinsonian activity, by inhibiting the release of glutamate from basal ganglia neurones. This study therefore examined the motor effects of lamotrigine in naive and reserpine-treated mice and its interactions with dopaminergic agonists. In normal mice, lamotrigine (5-80 mg/kg i.p.) decreased spontaneous locomotor activity with high doses (> or = 40 mg/kg) causing moderately severe impairment to posture and gait. In mice treated 24 h beforehand with reserpine (5 mg/kg i.p.), lamotrigine (5-40 mg/kg i.p.) had no effect on akinesia by itself and did not alter the locomotion induced with the selective dopamine D1 receptor agonist 2,3,4, 5-tetrahydro-7,8-dihydroxy-1-phenyl-1 H-3-benzazepine hydrochloride (SKF 38393, 30 mg/kg i.p.). By contrast, motor responses to the dopamine D2 receptor-selective agonist N-n-propyl-N-phenylethyl-p-(3-hydroxyphenyl)ethylamine (RU 24213, 5 mg/kg s.c.) and to the dopamine precursor L-3,4-dihydroxyphenylalanine (L-DOPA, 150 mg/kg i.p. in the presence of benserazide, 100 mg/kg i.p.), were significantly potentiated by 10 and 40 mg/kg i.p. lamotrigine respectively. It is suggested that lamotrigine may enhance the antiakinetic action of L-DOPA in parkinson-like mice by increasing motor responding mediated by dopamine D2 but not dopamine D1 receptors. This interaction profile of lamotrigine with dopamine D1 and D2 receptor mechanisms is opposite to what one sees with antagonists of glutamate receptors.     

Activation or frustration of anti-tumor responses by T-cell-based immune modulation

Cataleptogenic effects of haloperidol (1 mg/kg i.p.) in rats was antagonized by caffeine and theophylline (10-50 mg/kg i.p.), and by selective adenosine A2 receptor antagonist (3,7-dimethyl-1-propargylxanthine) (3 and 6 mg/kg i.p.). Selective A1-adenosine receptor antagonist (8-cyclopentyltheophylline) (1.5 and 3 mg/kg i.p.) was not able to reduce this effect of haloperidol. These results confirm the antagonistic interaction between adenosine A2A and dopamine D2 receptors, and suggest the involvement of adenosine A2 receptors in the mechanisms of catalepsy.