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R Samanin

Publications and source records attributed to R Samanin.

At least 19 recordsLinked to original sources
PubMed1992

Stimulation of 5-HT1A receptors in the dorsal hippocampus impairs acquisition and performance of a spatial task in a water maze.

8-Hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), a potent 5-HT1A receptor agonist, was infused in the dorsal hippocampus of rats and its effect on acquisition and performance of a 2-platform spatial discrimination task was studied using a water maze. The infusion (0.5 microliter/min) of 2 but not 0.4 microgram 8-OH-DPAT in the CA1 region of the dorsal hippocampus impaired rats' accuracy with no effect on latency (except day 3). At 5 micrograms 8-OH-DPAT impaired rats' accuracy and significantly increased choice latencies from day 2 to day 5 of the training period. The dose of 2 micrograms significantly increased the errors of omissions on the first day of training and animals which had received 5 micrograms 8-OH-DPAT made significantly more errors of omission on the first and second days of training. Intrahippocampal administration of 1 microgram spiroxatrine, a 5-HT1A receptor antagonist, antagonized the effect of 5 micrograms 8-OH-DPAT on accuracy and choice latency with no significant effect on the errors of omission on days 1 and 2 of training. Infusion of 2 and 5 micrograms 8-OH-DPAT in the dorsal hippocampus also impaired accuracy in well-trained rats. The results suggest that stimulation of 5-HT1A receptors in the CA1 region of the dorsal hippocampus causes an impairment of spatial discrimination in rats.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1992

Citalopram's ability to increase the extracellular concentrations of serotonin in the dorsal raphe prevents the drug's effect in the frontal cortex.

Administered intraperitoneally to rats at 1 mg/kg, citalopram, a potent and selective inhibitor of serotonin uptake, significantly increased dialysate serotonin in the dorsal raphe, but not in the frontal cortex. At 10 mg/kg citalopram had a greater effect on raphe serotonin and a moderate and short-lasting increase in the dialysate serotonin in the frontal cortex. Citalopram 1 mg/kg i.p. significantly increased the extracellular concentration of serotonin in the frontal cortex of rats which had received a continuous infusion of 1 microM methiothepine in the dorsal raphe, a condition which by itself did not change cortical serotonin concentrations. The results suggest that the ability of serotonin uptake inhibitors to enhance the extracellular concentrations of serotonin in the dorsal raphe attenuates the drug's effect in the frontal cortex.

Animals↗
PubMed1992

Role of 5-HT receptors in the effect of d-fenfluramine on feeding patterns in the rat.

The effect of d-fenfluramine, 1.5 mg/kg i.p., on meal patterns was studied in rats treated i.p. with 1 mg/kg metergoline or 0.5 mg/kg ritanserin or s.c. with 3 mg/kg (+/-)cyanopindolol. d-Fenfluramine significantly reduced eating rate, meal size and total intake in the first 4 h of testing and the effects were antagonized by metergoline. (+/-)Cyanopindolol reduced total intake and the effect of d-fenfluramine on this measure; the effect of d-fenfluramine on meal size (but not on eating rate) was also reduced by (+/-)cyanopindolol. Ritanserin only reduced the rate of eating and the effect of d-fenfluramine on this measure. The results suggest that 5-HT1 receptors, possibly of the 5-HT1B type, are involved in the ability of d-fenfluramine to cause satiety in freely feeding rats.

Animals↗
PubMed1992

Feeding pattern studies suggest that d-fenfluramine and sertraline specifically enhance the state of satiety in rats.

The effects of d-fenfluramine (1.5 mg/kg) and sertraline (10 mg/kg), administered intraperitoneally once daily for seven days were studied on feeding parameters of rats over various periods. On the first day of treatment both drugs markedly reduced meal size and meal duration during the first hour and, to a lesser extent, the first 4 h. No effects were seen later. The size and duration of eating bouts were also markedly reduced by both drugs in the first hour. There was no significant effect of either drug on meal frequency in any period. Only d-fenfluramine significantly reduced the rate of eating within 4 h from the start of testing. Sertraline, but not d-fenfluramine, markedly increased locomotor activity in the first 4 h after the start of testing. The d-fenfluramine effect on eating rate disappeared by the second day whereas total intake and meal size were still reduced on day five. By days six and seven however the d-fenfluramine-treated rats did not differ from the controls. During the seven-day treatment sertraline always reduced total food eaten and meal size but caused only transient changes of locomotor activity and eating rate. Since the effects of d-fenfluramine and sertraline on meal size and food intake could be separated from the effects on eating rate and arousal, it appears that at appropriate doses these drugs specifically increase the satiating effect of food. Tolerance to this effect appears to develop more rapidly for d-fenfluramine than for sertraline.

1-Naphthylamine↗
PubMed1992

8-Hydroxy-2-(di-n-propylamino)tetralin, a 5-HT1A receptor agonist, impairs performance in a passive avoidance task.

The effects of various subcutaneous doses (30, 100 and 300 micrograms/kg) of 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), a serotonin (5-HT)1A receptor agonist, were studied on the performance of rats in a one-trial passive avoidance task. When administered 30 min before the training trial and the retention test, 8-OH-DPAT significantly reduced retention latencies at all doses. Similar results were obtained when 8-OH-DPAT was administered before either the training trial or the retention test. When administered 5 min after the training trial, 100 and 300 micrograms/kg 8-OH-DPAT significantly reduced the retention latencies whereas 30 micrograms/kg caused a non-significant tendency to a reduction. A dose of 300 micrograms/kg 8-OH-DPAT significantly raised the thresholds for various responses (flinch, jump and vocalization) elicited by electric shock applied to the grid floor while 30 and 100 micrograms/kg had no effect. When administered 30 min before the retention test to rats that could choose between a punished and unpunished compartment, 8-OH-DPAT at 100 and 300 micrograms/kg facilitated re-entry to either compartment but, like control animals, most 8-OH-DPAT-treated animals preferred the unpunished compartment. Although the effects of 8-OH-DPAT on pain perception, general activity or emotional behavior may interfere with the performance of rats in the passive avoidance task, the results suggest that at 100 and 300 micrograms/kg 8-OH-DPAT interferes with mechanisms related to the acquisition and consolidation of memory.

5,7-Dihydroxytryptamine↗
PubMed1992

Antidepressant-like effect of neurotensin administered in the ventral tegmental area in the forced swimming test.

Locomotor activity and behaviour in the forced swimming test were examined in rats which had received neurotensin (0.5-5.0 micrograms) in the ventral tegmental area. Doses of 5 micrograms neurotensin but not lower increased the locomotor activity for at least 2 h. At 0.5 and 1.0 microgram neurotensin significantly increased the time the animals spent in struggling with no changes in general motor activity (swimming). The effect of 1.0 microgram neurotensin on struggling was completely antagonized by 0.5 microgram (-)-sulpiride administered in the posterior nucleus accumbens. The results suggest that activation of the mesolimbic dopamine system through administration of neurotensin in the ventral tegmental area produces antidepressant-like effects. The significance of these findings for a role of endogenous neurotensin in depression remains to be clarified.

Analysis of Variance↗
PubMed1992

Serotonin2 receptor agonists and serotonergic anorectic drugs affect rats' performance differently in a five-choice serial reaction time task.

A five-choice serial reaction time task was used to study the effects of serotonin (5-HT) receptor agonists and antagonists on accuracy of performance and food-motivated behaviour. Lysergic acid diethylamide (LSD), 0.1 mg/kg IP and quipazine, 2.5 mg/kg IP significantly reduced the percentage of correct responses and increased the percentage of omissions with no effect on other measures such as latency to collect the reinforcement or to respond correctly. The effects of LSD and quipazine were reversed by 1-2 mg/kg ritanserin, a potent 5-HT2 and 5-HT1C receptor antagonist. Metachlorophenylpiperazine (mCPP) 2.5 mg/kg IP, an agonist at 5-HT1B and 5-HT1C receptors, and d-fenfluramine (DF) 1.25 mg/kg IP, a releaser of 5-HT from nerve terminals and inhibitor of 5-HT uptake, increased the percentage of omissions and the latency to respond correctly or to collect the reinforcement with no effects on the correct responses. Effects similar to those of mCPP and DF were obtained by 60 min access to food before testing. Haloperidol, 0.1 mg/kg IP, did not affect the percentage of correct responses or the latency to collect the reinforcement, but significantly increased the proportion of errors of omission and the latency to respond correctly. The results show that 5-HT2 receptor agonists cause attentional disturbances at doses that have no marked effect on motivation for food or speed.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

The role of serotonin and dopamine in brain in the antidepressant-like effect of clonidine in the forced swimming test.

The effect of clonidine (0.1 mg/kg, i.p.), as a three-injection course, on behaviour in the forced swimming test was studied in rats injected intracerebroventricularly (i.c.v.) with 150 micrograms 5,7-dihydroxy-tryptamine (5,7-DHT) to destroy serotonin (5-HT) neurones or treated with 100 mg/kg (i.p.) (+/-)-sulpiride or 0.5 micrograms/0.5 microliter (-)-sulpiride in the nucleus accumbens. Clonidine significantly increased struggling and reduced floating and the effects were antagonized by both treatments with sulpiride but not by 5,7-DHT which markedly depleted 5-HT in brain. The results suggest that the mesolimbic dopaminergic system but not 5-HT neurones, plays a permissive role in the antidepressant-like effect of clonidine in the forced swimming test.

5,7-Dihydroxytryptamine↗
PubMed1992

Role of serotonin and catecholamines in brain in the feeding suppressant effect of fluoxetine.

The hypophagic effect of fluoxetine was studied in rats, injected intracerebroventricularly with 150 micrograms/20 microliters 5,7-dihydroxytryptamine, to destroy serotonin-containing neurones or 250 micrograms/20 microliters 6-hydroxydopamine, to destroy catecholamine-containing neurones. The effect of various serotonin receptor antagonists was assessed as well. Neither neurotoxin significantly modified the effect of 20 mg/kg (i.p.) fluoxetine on food intake. Metergoline (1-5 mg/kg), (-)-propranolol (16 mg/kg) and ICS 205-930 (0.1 and 1 mg/kg) did not modify the hypophagic effect of fluoxetine, while mianserin (1 and 5 mg/kg), ritanserin (0.5 and 1 mg/kg) and xylamidine (3 mg/kg) slightly but significantly reduced it. While the mechanism by which some 5-HT receptor antagonists modify the effect of fluoxetine remains to be elucidated, it seems clear that 5-HT receptors hardly have any significant role in the ability of the drug to suppress food intake.

5,7-Dihydroxytryptamine↗
PubMed1992

Tianeptine increases the extracellular concentrations of dopamine in the nucleus accumbens by a serotonin-independent mechanism.

The effect of various doses of tianeptine on the extracellular concentrations of dopamine was studied in the striatum and nucleus accumbens of the rat. At 5 (but not 2.5) mg/kg intraperitoneally, tianeptine increased the extracellular dopamine only in the nucleus accumbens. At 10 mg/kg, the effect was also seen in the striatum but it was less marked and shorter-lasting. At 10 mg/kg (i.p.), tianeptine significantly raised the extracellular concentrations of dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in both regions. The effect of 10 mg/kg tianeptine on dopamine and its metabolites was not significantly changed in animals which had received this dose twice daily for 15 days. Intracerebroventricular administration of 150 micrograms/20 microliters 5,7-dihydroxytryptamine, which markedly depleted serotonin in the brain, did not modify the effect of 10 mg/kg tianeptine on the extracellular concentrations of dopamine and HVA in the nucleus accumbens but reduced the effect on DOPAC. Various doses of tianeptine (1, 3 and 10 mg/kg i.p.) did not change the synthesis of serotonin and dopamine in the striatum and nucleus accumbens. The results show that tianeptine increased the extracellular concentrations of dopamine more in the nucleus accumbens than in striatum. The effect on the output of DA in the nucleus accumbens could be involved in the antidepressant activity of tianeptine.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1992

GAP-43 mRNA localization in the rat hippocampus CA3 field.

Gene expression of the axonal growth-associated protein, GAP-43, has been studied in the adult rat brain by in situ hybridization histochemistry. This protein is synthesized at high levels in neuronal somata in immature and regenerating neurons, but after establishment of mature synaptic relations its synthesis generally declines sharply, thus providing a marker denoting propensity for exhibiting synaptic plasticity. Detailed examination of the distribution of mRNA for GAP-43 in rat hippocampus is selectively and robustly expressed in the pyramidal neurons of field CA3 and, to a lesser extent, the polymorph neurons of the hilus of the dentate gyrus. Additional hippocampal regions of moderate expression include the tenia tecta and the subicular and entorhinal fields, but CA1 and CA2 are strikingly lower in signal. The significance of this pattern of localization is considered in the context of the phosphorylation of GAP-43 and its role in influencing synaptic events underlying the establishment and maintenance of long-term potentiation and plasticity in the hippocampus.

Animals↗
PubMed1992

Somatostatin release is enhanced in the hippocampus of partially and fully kindled rats.

The release of somatostatin (somatostatin-like immunoreactivity) from hippocampal slices during the development of hippocampal kindling in rats was measured under resting and depolarizing conditions. Preliminary experiments in naive rats showed that the spontaneous efflux of somatostatin (4.0 +/- 0.3 fmol/ml every 10 min) was independent of external Ca2+ but was reduced to 71.5 +/- 6% of baseline (P < 0.05) during 20 min incubation with 5 microM tetrodotoxin. Neuronal depolarization with 25, 50 and 100 mM KCl induced a Ca(2+)-dependent somatostatin release, respectively 4.3 +/- 0.4, 16.7 +/- 1.6 and 22.0 +/- 1.3 times baseline (P < 0.01). Veratridine caused a dose-dependent Ca2+ and tetrodotoxin (5 microM) sensitive release ranging from 6.5 +/- 0.1 to 13.0 +/- 1.4 times baseline at 1.4 microM and 50 microM respectively (P < 0.01). One week after the last of three consecutive stage 5 seizures (full seizure expression) or 48 h after the last stage 2 stimulation (preconvulsive stage), 50 mM KCl-induced somatostatin release was significantly higher (1.8 +/- 0.1, P < 0.01) than in shams (animals implanted with electrodes but not stimulated) in the stimulated and contralateral hippocampus. Somatostatin release measured under resting conditions was increased by 1.5 times in the stimulated hippocampus at stage 2 (P < 0.05) and by 2.2 and 1.7 times in both hippocampi at stage 5 (P < 0.01). Forty-eight hours after the induction of a single afterdischarge no significant changes were found in either spontaneous or 50 mM KCl-induced release of somatostatin.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

8-Hydroxy-2-(di-n-propylamino)tetralin impairs spatial learning in a water maze: role of postsynaptic 5-HT1A receptors.

1. The effects of 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), a 5-HT1A receptor agonist, on place navigation was studied by use of two spatial tasks in a water maze. 2. In the first experiment, rats treated subcutaneously with 100 and 300 (but not 30) micrograms kg-1 8-OH-DPAT were impaired in their ability to locate a hidden platform. The probe test confirmed the impairment of spatial navigation but the effect (time spent in the training quadrant) was quantitatively different, depending on whether 8-OH-DPAT was administered only before each training session, only before the probe test or in both conditions. 3. In the second experiment, rats received 150 micrograms 5,7-dihydroxytryptamine (5,7-DHT) intracerebroventricularly to destroy 5-hydroxytryptamine (5-HT)-containing neurones and 24 days later were examined for choice accuracy in a two-platform spatial discrimination task. 4. At 100 (but not 30) micrograms kg-1 8-OH-DPAT impaired rats' accuracy with no effect on latency and no errors of omission. In 5,7-DHT-treated rats, this dose had a greater effect, including errors of omission. Sham-operated rats injected with 300 micrograms kg-1 8-OH-DPAT were markedly impaired in accuracy but they had longer latencies and made more errors than controls. All the effects were increased in 5,7-DHT treated rats. 5. The results suggest that, at doses causing no apparent changes in motor behaviour or motivation, 8-OH-DPAT impairs spatial navigation by stimulating postsynaptic 5-HT1A receptors in the rat brain.

5,7-Dihydroxytryptamine↗
PubMed1992

Effect of amineptine on regional extracellular concentrations of dopamine and noradrenaline in the rat brain.

The effect of amineptine (1.25-20 mg/kg i.p.), an antidepressant inhibiting dopamine uptake, on extracellular concentrations of dopamine was studied in the rat striatum and nucleus accumbens by using the microdialysis technique and two Ca++ concentrations (1.26 and 3.4 mM) in the perfusion medium. In one experiment the effect of amineptine was studied on extracellular concentrations of dopamine and noradrenaline in the frontal cortex perfused with a medium containing 1.26 mM Ca++. Basal extracellular concentrations of dopamine in the striatum and nucleus accumbens were significantly higher at 3.4 mM Ca++. At 5 to 20 mg/kg, amineptine dose-dependently increased extracellular dopamine in the striatum and nucleus accumbens. No differences were found in the effect of amineptine in the two brain regions at the two calcium concentrations. When extracellular dopamine was expressed as a percentage of basal values, amineptine (20 mg/kg) caused greater increases in rats perfused with 1.26 mM Ca++ than in rats perfused with 3.4 mM Ca++ in both brain regions. A similar effect was found when 10 microM amineptine was infused through the dialysis fiber. The effect of 10 mg/kg i.p. of amineptine on dopamine output in the two brain regions was prevented by infusing 1 microM tetrodotoxin in the dialysis fiber. In the frontal cortex, 10 and 20 mg/kg of amineptine significantly raised dopamine and noradrenaline concentrations, whereas 5 mg/kg only increased noradrenaline output significantly. At 10 mg/kg i.p., amineptine also increased extracellular noradrenaline in the dorsal hippocampus. Amineptine had no consistent effects on the concentrations of dihydroxyphenylacetic acid and homovanillic acid in the various brain regions.(ABSTRACT TRUNCATED AT 250 WORDS)

3,4-Dihydroxyphenylacetic Acid↗
PubMed1991

Increased preproneuropeptide Y mRNA in the rat hippocampus during the development of hippocampal kindling: comparison with the expression of preprosomatostatin mRNA.

The levels of preproneuropeptide Y (ppNPY) mRNA and preprosomatostatin (ppSOM) mRNA were analyzed in different brain regions during the development of hippocampal kindling in rats. ppNPY mRNA levels were markedly elevated in the dorsal hippocampus bilaterally, two days after stage 2 (preconvulsive stage) and stage 5 (full seizure expression). The contents of ppSOM mRNA were slightly, although not significantly, increased in the dorsal hippocampus at stage 2 whereas a significant increase was observed in the ipsilateral hippocampus of fully kindled rats. ppNPY and ppSOM mRNA levels were unchanged in the cortex and striatum at both stages of kindling. These results show that an increased synthesis of somatostatin and neuropeptide Y, with a greater effect for the latter, occurs during hippocampal kindling in rats. The relative role of the two peptides in the development and expression of kindling phenomenon remains to be elucidated.

Animals↗
PubMed1991

Changes in pre- and postsynaptic components of noradrenergic transmission in hippocampal kindling in rats.

We investigated whether modifications in noradrenergic neurotransmission occurred during the development of hippocampal kindling in rats. We measured the release of [3H]norepinephrine (NE) induced by field-electrical stimulation, NE-stimulation of inositol phosphates [( 3H]IP) accumulation in the presence of LiCl and isoproterenol-induced accumulation of cAMP in hippocampal slices taken from rats electrically kindled at stages 2 and 5 in the dorsal hippocampus. One week after the last of at least 3 consecutive stage 5 seizures or 48 h after the last stage 2 stimulation, 2 min electrical stimulation of stratum pyramidale CA1-CA3 or dentate gyrus (DG) slices from kindled and contralateral hippocampi induced frequency-dependent NE release (respectively 2, 4 and 8 times spontaneous release measured at 2, 5 and 10 Hz) which did not significantly differ from that observed in shams (implanted with electrodes but not stimulated). Basal release of NE from kindled and sham-treated rats did not differ either. Isoproterenol induced a dose-dependent increase above basal cAMP concentration ranging from 40% at 0.01 microM to 180% at 10 microM (P less than 0.01, Dunnett's test) which did not differ between stages 2 and 5 and sham-hippocampi. NE (1-1000 microM) induced a dose-dependent, prazosin-sensitive increase in [3H]IP accumulation in the hippocampal slices. A significantly higher increase was found at stages 2 (P less than 0.05, Tukey's test) and 5 (P less than 0.05 and P less than 0.01, Tukey's test) compared to shams at all doses studied.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Role of 5-HT receptors in the effect of d-fenfluramine on gastric emptying and feeding behaviour as examined in the runway test.

In one experiment, the effect of d-fenfluramine (DF) on gastric emptying was studied in rats treated i.p. with metergoline, a non-selective serotonin (5-HT) receptor antagonist, ritanserin, a selective 5-HT2 and 5-HT1C receptor antagonist, and xylamidine, a 5-HT antagonist which has poor access to the brain. Metergoline (1 mg/kg) but not ritanserin (0.5 mg/kg) or xylamidine (3 mg/kg) blocked the effect of 2.5 mg/kg DF studied 2 and 4 h after injection. In a second experiment, we studied the ability of metergoline to antagonise the effect of DF, administered after a meal, on runway performance, food intake and gastric emptying assessed 4 h later. Metergoline at a dose of 1 mg/kg did not antagonise the effect of DF (2.5 mg/kg) on runway performance but completely blocked the effect on gastric emptying. The data clearly show that DF delays gastric emptying by indirectly activating 5-HT1 receptors; this effect is not important for the ability of DF to reduce runway performance and food intake when the drug is injected after a pre-feeding period. While there is evidence that DF hastens the termination of the meal by a 5-HT mechanism, the data suggest that DF may prolong the satiating effect of food during the post-absorptive phase by mechanisms other than 5-HT.

Animals↗