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M Papp

Publications and source records attributed to M Papp.

At least 37 records · Page 2Linked to original sources
PubMed1996

Differential effects of agents acting at various sites of the NMDA receptor complex in a place preference conditioning model.

A conditioned place preference paradigm was used to assess the potential rewarding properties of the uncompetitive NMDA receptor antagonist, MK-801 (dizolcipine), the two competitive NMDA receptor antagonists, CGP 37849 (DL-(E)-2-amino-4-methyl-5-phosphono-3-pentonoic acid) and its (R)-enantiomer CGP 40116, as well as the partial agonist at strychnine-insensitive glycine receptors, ACPC (1-aminocyclopropanecarboxylic acid). MK-801 (0.3 mg/kg), CGP 37849 (1.25-10 mg/kg) and CGP 40116 (1.25-10 mg/kg), administered in association with either the initially non-preferred or initially preferred side of the two-arm chamber, caused a significant increase in the time spent on that side in a post-conditioning test. In contrast, ACPC did not support the conditioned place preference. Thus, the time spent on the drug-associated side following conditioning with ACPC (50-400 mg/kg) did not significantly differ from that measured in the pre-conditioning test, irrespective of whether it was associated with the initially non-preferred black side or the initially preferred white side. These results are consistent with both clinical and pre-clinical data demonstrating differences in psychopharmacological properties among compounds acting at the multiple, allosteric regulatory sites on the NMDA receptor complex. Moreover, these results indicate that the abuse potential of ACPC, which acts as a functional NMDA receptor antagonist, may be lower than that of either uncompetitive or competitive NMDA receptor antagonists.

2-Amino-5-phosphonovalerate↗
PubMed1996

Antidepressant-like effects of 1-aminocyclopropanecarboxylic acid and D-cycloserine in an animal model of depression.

Antidepressant activity of partial agonists at strychnine-insensitive glycine receptors, 1-aminocyclopropanecarboxylic acid (ACPC) and D-cycloserine, was studied in a chronic mild stress model of depression. In this model, a substantial decrease in consumption of a palatable sucrose solution is observed over time in rats subjected to a variety of mild stressors. This decrement can be reversed by chronic administration of antidepressant drugs. Chronic (5 weeks) treatment with ACPC gradually reversed chronic mild stress-induced reductions in sucrose consumption, and the magnitude of this effect was comparable to that observed following similar administration of imipramine (10 mg/kg). The time-course for reversal of chronic mild stress-induced deficits in sucrose consumption by ACPC was dose-dependent. Thus, the first statistically significant effect of the low dose of ACPC (100 mg/kg) was observed after four weeks of treatment (comparable to the 3-5 weeks required for imipramine), while only two weeks of treatment was required in the group receiving a higher dose (200 mg/kg) of ACPC. Like imipramine, reversal of chronic mild stress-induced deficits in sucrose consumption by ACPC persisted for at least one week following cessation of treatment. The effects of chronic D-cycloserine were variable, and apparently not dose-related in the chronic mild stress model. D-cycloserine (10 mg/kg) increased sucrose intake in stressed animals, but the magnitude of this effect was smaller than in either imipramine or ACPC treated animals. Lower (2.5 mg/kg) and higher (40, 100 mg/kg) doses of D-cycloserine were ineffective. These results suggest that ACPC may have antidepressant properties comparable to conventional drugs, but with a faster onset of action.

Animals↗
PubMed1996

[Critical evaluation of factors influencing pancreatic cytoprotection].

The authors give a brief survey on adaptive pancreatic cytoprotection and vasoprotection in the framework of which noxious agents and factors of defensive mechanism are made known and critically evaluated. In development of acute pancreatitis intraacinar redistribution of lysosomal hydrolases, colocalization of digestive and lysosomal enzymes, escape of digestive and lysosomal enzymes from pancreatic ductal system into the interstitium, inflammatory modulators released from macrophages and evoking local inflammation, ischaemia, furthermore feedback regulation of pancreatic secretion can be regarded as motives. Factors of defensive mechanism include prostaglandins, nitric oxide and the unobstructed, juice flow which promote the repair of injured membranes in acinar and vascular endothelial cells, respectively. Their whole sum may be called adaptive pancreatic cyto- and vasoprotection or pancreatic "self-defence mechanism".

Acute Disease↗
PubMed1996

Pharmacological validation of the chronic mild stress model of depression.

Chronic exposure to mild unpredictable stress has previously been found to depress the consumption of palatable sweet solutions, and this effect was reversed by chronic treatment with a variety of antidepressant drugs. The present study reports three experiments examining the effects in this model of further antidepressant agents, a number of non-antidepressants, and some compounds of indeterminate clinical status. Male Wistar rats were exposed sequentially to a variety of mild stressors, which continued throught the experiments. Drug treatments commenced after 3 weeks of stress, by which time intake of a 1% sucrose solution (measured in a 1-h weekly test) was significantly depressed. No drug effects were seen after 1 week of treatment. Normal levels of sucrose drinking were seen following chronic (3-5 weeks) of treatment with the antidepressants imipramine (10 mg/kg per day), brofaromine (20 mg/kg per day), and buspirone (5 mg/kg per day). Positive effects were also seen following chronic treatment with atropine (1 mg/kg per day) and mepyramine (5 mg/kg per day). d-Amphetamine (1 and 3 mg/kg per day), the neuroleptics haloperidol and chlorprothixene (1 mg/kg per day), and morphine (administered at doses rising to 110 mg/kg per day) were ineffective; amphetamine (3 mg/kg) and morphine decreased sucrose intake in control animals. No inferences can be drawn from the effects of atropine and mepyramine, which are of indeterminate clinical status; data from the other seven agents tested support the hypothesis that the chronic mild stress model responds appropriately to antidepressant and non-antidepressant agents.

Animals↗
PubMed1996

Decreased hedonic responsiveness following chronic mild stress is not secondary to loss of body weight.

Chronic exposure to mild unpredictable stress (CMS) has previously been found to decrease hedonic responsiveness, as measured by the consumption of palatable sweet solutions or sensitivity to brain stimulation reward. These effects are reversed by chronic treatment with antidepressant drugs, and the CMS procedure has been proposed as a relatively valid animal model of depression. It has recently been suggested that the behavioural effects of CMS may be secondary to loss of body weight. This article collates data from five laboratories using the CMS procedure. Data are presented from seven studies using five different rat strains, as well as CD1 mice. Three-week exposure to CMS significantly decreased sucrose consumption by Lister hooded, PVG hooded, Wistar, and Wistar WU rats, and by CD1 mice, and sensitivity to brain stimulation reward in Ibm:Ro Ro rats. Weight loss in different experiments varied between 0 and 10%. Hedonic sensitivity relative to body weight (e.g., mg sucrose/g body weight) decreased significantly in all experiments. Animals maintained on a restricted feeding regime lost weight but did not show decreases in sucrose intake. It is concluded that decreased hedonic sensitivity following chronic mild stress cannot be attributed to loss of body weight.

Animals↗
PubMed1996

Effect of chronic mild stress on circadian rhythms in the locomotor activity in rats.

The purpose of this study was to assess whether the chronic mild stress (CMS) procedure, as a realistic animal model of depression, affects the rhythms of the locomotor activity in rats. Rhythm parameters (period, mesor, amplitude, acrophase, and percent rhythm) were estimated from the best-fitted cosine function curves. Period is the length, mesor is the mean level, amplitude (A) is the extent, acrophase is the timing of the rhythm; percent rhythm represents the variability estimated by the cosine regression and expressed as a percentage of the total variability of raw data. The animals were kept on the 12 L : 12 D cycle during 13 weeks of the experiment and subjected to CMS for first 4 weeks. In week 5 the rats were under the constant light for 24 h a day (LL), and in week 9, under the constant darkness (DD). In LD 12:12 CMS decreased the activity in the dark phase by approximately 50% (p < 0.01) and did not change the activity in the light phase, resulting in a drop of the 24 h activity by about 40% in comparison to controls. The amplitude of diurnal variations of the activity was highly statistically different from zero at p(A = 0) < 0.0001, and the percent rhythm was in range of 40-75% in both the CMS and control groups. The mesor and the amplitude of the diurnal rhythm (with a period of 24 h) in the CMS rats were significantly (p < 0.001) lower than those in the control. In LL, the activity of both groups was diminished about 50% during the subjective dark phase. On the other hand, in the subjective light phase the activity of CMS rats only was diminished. The percent rhythm for the CMS and control rats was 30 and 58%, respectively, and values of mesor, amplitude, and acrophase for both groups were highly statistically different. In DD, the activity in the CMS group was statistically significantly lower in both the subjective dark and light phases. In contrast to the results from LL, the cosine curves from DD were similarly shifted in relation to the subjective light-dark cycle. After a restoration of the LD cycle the levels of the 24-h activity of both groups became equal in the 13th week, but the light and dark phase differences between the groups were still statistically significant (p < 0.05). The present results indicate that CMS exerts distinct and prolonged disturbances of the diurnal and circadian rhythms of the locomotor activity in the rats.

Animals↗
PubMed1996

Discriminative stimulus effects of the NMDA receptor antagonists MK-801 and CGP 37849 in rats.

Rats were trained to discriminate MK-801 (0.05 mg/kg, IP), an uncompetitive, or CGP 37849 (3 mg/kg, IP), a competitive NMDA receptor antagonist from saline, using a two-lever, operant drug discrimination paradigm. In generalization tests the role of dopaminergic and serotonergic systems in the discriminative stimulus effects produced by both NMDA receptor antagonists was studied with amphetamine (0.5 mg/kg), cocaine (5.0 and 7.5 mg/kg), and fenfluramine (2.5 and 5.0 mg/kg). Additionally, memantine (5.0, 7.5 and 10.0 mg/kg), an uncompetitive NMDA receptor antagonist, was tested. The discriminative stimuli produced by MK-801 and CGP 37849 were not generalized to each other. Among the tested drugs only memantine generalized to the MK-801 discriminative stimulus. None of the tested drugs showed CGP 37849-like discriminative stimulus properties. The different mechanisms underlying NMDA antagonism by MK-801 and GP 37849 might explain the observed lack of cross-generalization. The results suggest that dopaminergic and serotonergic systems are not of major importance in the discriminative stimulus effects produced by both MK-801 and CGP 37849.

2-Amino-5-phosphonovalerate↗
PubMed1996

Age-dependent influence of octreotide on stimulated pancreatic growth in the postnatal period of rats.

OBJECTIVE: To investigate the effect of long-acting octreotide (SMS 201-995) on the plasma growth hormone level in preweaning rats and to study the growth and composition of the exocrine pancreas in these rats after stimulation by caerulein- and camostate-induced endogenous cholecystokinin (CCK). METHODS: Wistar rats of both sexes were treated as littermate pairs in two periods of postnatal age, from days 1 to 11 and from days 11 to 21. To stimulate pancreatic growth, caerulein (3 micrograms/kg subcutaneously three times daily) was given from days 1 to 11, and oral camostate (200 mg/kg given once daily) or CCK-8 (10 micrograms/kg subcutaneously three times daily) was administered from days 11 to 21. Octreotide (6 or 15 micrograms/kg subcutaneously twice daily) was administered alone or in combination with caerulein or camostate. The rats were exsanguinated on days 11 or 21, and each pancreas was removed, weighed and analysed. RESULTS: Caerulein stimulated pancreatic growth and raised the trypsin concentration; camostate induced pancreatic hypertrophy and hyperplasia. By day 11, octreotide had decreased the plasma growth hormone level and the basal pancreatic trypsin concentration and content. Given in combination with caerulein, octreotide reduced the growth hormone level and the stimulated trypsin and DNA contents. By day 21, rats treated with octreotide in the camostate group showed a reduced basal pancreatic trypsin concentration and a decreased basal trypsin content (although the changes were not significant). Plasma growth hormone levels were not significantly reduced. CONCLUSION: The antitrophic pancreatic action of octreotide and its plasma growth hormone-lowering effect were shown in rats during the first 10 days after birth. These effects were less notable from days 11 to 21, a period when CCK receptors increase in number and components of the stimulus-secretion mechanism are mature.

Analysis of Variance↗
PubMed1995

The effect of 5-HT1A receptor ligands in a chronic mild stress model of depression.

Antidepressant properties of 5-HT1A receptor ligands (the full agonist 8-OH-DPAT, the partial agonists ipsapirone and buspirone, and the selective antagonist WAY 100135) were studied in a chronic mild stress model of depression. In this model, rats subjected to a variety of mild stressors for a prolonged period of time show a substantial decrease in the consumption of a 1% sucrose solution (anhedonia), an effect being sensitive to repeated treatment with antidepressant drugs. In the present study we found that the stress-induced deficit in the sucrose intake was gradually reversed by chronic (3-5 weeks) administration of buspirone (2.5 and 5 mg/kg, i.p., b.i.d.) or WAY 100135 (10 mg/kg, s.c., b.i.d.), but not 8-OH-DPAT (0.5 mg/kg, s.c., b.i.d.) or ipsapirone (5 mg/kg i.p., b.i.d.). The magnitude of the effect of buspirone and WAY 100135 was comparable to that observed following similar administration of the antidepressant drugs imipramine (10 mg/kg i.p.) or citalopram (10 mg/kg i.p.). Increases in the sucrose intake following chronic treatment with buspirone, WAY 100135, imipramine and citalopram were specific to the stressed animals; the behaviour of control non-stressed animals was unchanged by any drug. These results suggest that buspirone and WAY 100135 may have antidepressant properties. Possible links between the anti-anhedonic effect of these drugs and their interaction with 5-HT1A receptors and/or the dopamine system are discussed.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1995

The effect of chronic treatment with imipramine on the immunoreactivity of animals subjected to a chronic mild stress model of depression.

A depression-like state was induced in Wistar rats by chronic (3-week) exposure to very mild, unpredictable stress, which led to diminished food consumption and diminished preference for sweet drinks (anhedonia). Anhedonia was then abolished by 5 weeks of daily administration of imipramine to the continually stressed animals. One day after the last drug injection and stressful event, a statistically significant decrease in the proliferative activity of splenocytes to Con A stimulation in vitro was observed in those animals. Eight weeks of stress (without antidepressant therapy) affected likewise, but in a less potent and non-significant manner, the activity of splenocytes. Administration of imipramine alone for a period of 5 weeks did not modify the activity of these cells.

Animals↗
PubMed1995

The effect of chronic treatment with imipramine on the responsiveness of hippocampal CA1 neurons to phenylephrine and serotonin in a chronic mild stress model of depression.

The effect of chronic mild stress (CMS) and chronic treatment with the tricyclic antidepressant drug imipramine (10 mg/kg/day for 5 weeks) on neuronal responsiveness to the alpha 1-noradrenergic agonist phenylephrine and serotonin (5-HT) was examined ex vivo, in the CA1 cell layer of the rat hippocampal slice preparation. We corroborated some previous findings that CMS, which had been used as an animal model of depression, decreased the consumption of a 1% sucrose solution and that that effect was reversed by chronic administration of imipramine. Imipramine did not change the sucrose consumption in control animals. In both control and stressed animals, phenylephrine (5 microM) and 5-HT (10 microM) attenuated the amplitude of the population spikes evoked in the CA1 pyramidal cell layer by stimulation of Schaffer collateral/commissural fibers. Those inhibitory effects of phenylephrine and 5-HT were significantly potentiated by chronic treatment with imipramine. The imipramine-induced potentiation was similar in slices from control and stressed animals. These results suggest that the imipramine-induced functional changes in alpha 1-noradrenergic and serotonergic receptors in the hippocampus are not involved in the anti-anhedonic effect of chronic imipramine administration in the CMS model of depression.

Animals↗
PubMed1995

The effect of the long-acting somatostatin analogue octreotide on caerulein-induced pancreatic injuries in rats.

The efficacy of long acting somatostatin analogue, octreotide acetate (SMS 201-995) on the caerulein-induced acute pancreatitis and on the regeneration of the gland was examined. The effect of the drug on the acute injury was examined at 6 and 24 hours following the intervention, while the regeneration was examined on Day 3 and Day 5 in all cases by determination of plasma amylase levels and by analysis of the pancreatic tissue. The use of octreotide could not counteract the occurrence of acute pancreatitis, however, it has some benefit as seen by it's ability to moderate the increases of serum amylase levels. During the examination of pancreatic regeneration it was found that the weight of the pancrease decreased and this was not affected by octreotide. As a matter of fact, the octreotide coadministered with caerulein counteracted the caerulein-induced increase of pancreatic DNA content and therefore acted against the reactive pancreatic hyperplasia. Thus long term administration of octreotide in acute pancreatic injury may not be rational.

Acute Disease↗
PubMed1994

Antidepressant activity of non-competitive and competitive NMDA receptor antagonists in a chronic mild stress model of depression.

The antidepressant properties of the non-competitive NMDA receptor antagonist, MK-801 (dizocilpine), and the competitive NMDA receptor antagonist, CGP 37849 (DL-(E)-2-amino-4-methyl-5-phosphono-3-pentonoic acid) and its (R)-enantiomer CGP 40116, were studied in a chronic mild stress model of depression. In this model, animals subjected to a variety of mild stressors for a prolonged period of time show a substantial decrease in the consumption of palatable sucrose solution (anhedonia). It was previously demonstrated that the chronic mild stress-induced anhedonia can be reversed by chronic treatment with various antidepressant drugs. In this study we found that the stress-induced deficit in sucrose intake was gradually reversed by chronic (4-5 weeks) treatment with MK-801 (0.3 mg/kg i.p.), CGP 37849 (5 mg/kg i.p.) and CGP (25 mg/kg p.o.). The magnitude of this effect and its time course were comparable to those observed following similar administration of imipramine (10 mg/kg i.p. or p.o.). The increase in sucrose intake following chronic administration of imipramine and NMDA receptor antagonists was specific to stressed animals; the behaviour of non-stressed controls was unchanged by any of the drugs tested. These results confirm those of previous studies, carried out on 'normal' animals, suggesting that antagonists of NMDA receptors may have antidepressant properties.

2-Amino-5-phosphonovalerate↗
PubMed1994

Reversal by imipramine of beta-adrenoceptor up-regulation induced in a chronic mild stress model of depression.

Male Wistar rats were subjected to a chronic mild stress procedure involving different stress stimuli applied for 8 weeks. During this time the consumption of 1% sucrose solution was monitored at weekly intervals. After the first 3 weeks, when stressed animals displayed a reduction of sucrose consumption, the control and stressed groups were divided into subgroups receiving daily placebo or imipramine (10 mg/kg/day) treatment. After 5 weeks of treatment, 24 h after the last injection, the rats were killed and beta-adrenoceptor density and affinity in cortical membrane preparations and the accumulation of cyclic AMP in cortical slices stimulated with noradrenaline were assessed. While in stressed placebo-treated rats the sucrose consumption remained reduced, in the imipramine-treated group the level of consumption gradually returned to control values. The stressed placebo-treated rats also displayed an increase in cortical beta-adrenoceptor density (by 34%) with no changes in affinity, and an increase (22%) in the cyclic AMP response to noradrenaline in cortical slices. Imipramine, which in non-stressed rats did not affect sucrose intake but depressed the beta-adrenoceptor density and the cyclic AMP response, reversed the stress-induced decrease in sucrose consumption and the increase in the beta-adrenoceptor density; at physiological noradrenaline concentrations it also reduced the enhanced cyclic AMP response. The results suggest that the chronic mild stress procedure produces behavioral and biochemical changes consistent with a realistic model of depression in animals.

Adenylyl Cyclases↗
PubMed1994

Effects of imipramine on serotonergic and beta-adrenergic receptor binding in a realistic animal model of depression.

Chronic exposure to mild unpredictable stress (CMS) has previously been found to cause an antidepressant-reversible decrease in the consumption of palatable sweet solutions. In the present study, in addition to confirming these behavioural observations, the binding properties of cortical beta-adrenergic and 5HT2 receptors, and hippocampal 5HT1A receptors were studied (using the ligands [3H]-dihydroalprenolol, [3H]-ketanserin and [3H]-8-OH-DPAT, respectively), following 7 weeks of CMS and 4 weeks of imipramine treatment (10 mg/kg per day). CMS increased Bmax for all three receptor systems. Imipramine decreased Bmax, reversing the effect of CMS, for beta-adrenergic and 5HT2 receptor binding, but increased Bmax for 5HT1A receptor binding. KDs were unaffected by either treatment. The beta-receptor and 5HT2 receptor binding data are consistent with accounts of antidepressant action derived from studies in normal animals, but the 5HT1A receptor binding data are more difficult to reconcile. In no case was there a good correlation between receptor binding and behavioural data.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1994

Parallel changes in dopamine D2 receptor binding in limbic forebrain associated with chronic mild stress-induced anhedonia and its reversal by imipramine.

Chronic sequential exposure to a variety of mild stressors has previously been found to cause an antidepressant-reversible decrease in the consumption of palatable sweet solutions, associated with abnormalities of dopaminergic neurotransmission in the nucleus accumbens. In the present study, 5 weeks of treatment with imipramine (10 mg/kg b.i.d.) reversed the decreased sucrose intake of rats exposed to chronic mild stress. Stress also caused a decrease in D2-receptor binding in the limbic forebrain (but not the striatum), which was completely reversed by imipramine. In nonstressed animals, imipramine decreased D1-receptor binding in both regions. However, in stressed animals, imipramine did not significantly alter D1-receptor binding in either area. Stress alone slightly increased D1-receptor binding, in striatum only. Scatchard analysis showed that all changes in receptor binding resulted from changes in receptor number (Bmax) rather than receptor affinity (KD). The results support the hypothesis that changes in D2-receptor function in the nucleus accumbens are responsible for chronic mild stress-induced anhedonia and its reversal by antidepressant drugs. They do not support the hypothesis that the sensitization of D2-receptors seen following chronic antidepressant treatment is caused by a down-regulation of D1-receptors.

Animals↗