Biomedical subjects

L Allikmets

Publications and source records attributed to L Allikmets.

At least 19 recordsLinked to original sources

PubMed2002

1-(1-naphthyl)-piperazine, a mixed 5-HT1A and 5-HT2A/2C receptor ligand, elicits an anxiolytic-like effect in the open-field test without changes in 5-HT metabolism.

The effects of acute 1-(1-naphthyl)-piperazine (1-NP, 2 mg/kg i.p.) on rat open-field and social interaction behaviors were studied followed by postmortem and in vivo microdialysis measurement of serotonin (5-HT) and 5-hydroxyidolacetic acid (5-HIAA) content. 1-NP treatment elicited an anxiolytic-like effect in the open-field test, which was not modified by citalopram (5 mg/kg i.p.) challenge. A statistically insignificant tendency toward prolongation of the social interaction time was also found. The only significant change in the postmortem experiment was found in the striatum: 5-HIAA content was reduced after combined 1-NP plus citalopram treatment. Using the in vivo microdialysis technique, no difference in the 5-HT or 5-HIAA output between the treatment groups was found in the frontal cortex of anaesthetized rats. Our present study demonstrates the anxiolytic-like properties of 1-NP in the open-field test, but this effect is irrelevant to changes in 5-HT metabolism.

Analysis of Variance↗

PubMed2001

Neuropeptide Y Y(5) receptor antagonist CGP71683A: the effects on food intake and anxiety-related behavior in the rat.

The effects of neuropeptide Y Y(5) receptor antagonist (trans-naphtalene-1-sulphonic acid [4-[(4-amino-quinazolin-2-ylamino)-methyl]-cyclohexylmethyl]-amide hydrochloride; CGP71683A), on food intake, anxiety and locomotor activity were studied. CGP71683A (1-10 mg/kg, i.p.) dose-dependently decreased nocturnal and fasting-induced food intake. CGP71683A did not have an anxiogenic-like effect in the rat social interaction test. In the elevated plus-maze test, where novel neuropeptide Y Y(1) receptor antagonist (2R)-5-([amino(imino)methyl)amino)-2-[(2.2-diphenylacetyl)-amino]-N-[(1R)-1-(4-hydroxyphenyl)ethyl-pentanamide (H 409/22) had anxiogenic-like effect, CGP71683A was inactive. In the open-field test, carried out immediately after the elevated plus-maze test, CGP71683A inhibited horizontal and vertical activity. CGP71683A did modify the habituation of locomotor response in novel environment. These data show that the inhibition of food intake induced by CGP71683A could not be explained by increased fearfulness, a state that is induced by neuropeptide Y Y(1) receptor antagonists. Thus, our data, obtained with first neuropeptide Y Y(5) receptor antagonist CGP71683A, suggest that in contrast to the neuropeptide Y Y(1) receptor, Y(5) receptor is not involved in tonic neuropeptide Y-induced anxiolysis.

Amides↗

PubMed2001

Acute trazodone and quipazine treatment attenuates apomorphine-induced aggressive behaviour in male rats without major impact on emotional behaviour or monoamine content post mortem.

We have studied the effect of acute trazodone (3--20 mg kg(-1)) and quipazine (1--3 mg kg(-1)) treatment on the apomorphine-induced (1 mg kg(-1), once daily over 2 weeks) aggressive behaviour in male Wistar rats. All doses of trazodone and quipazine tested attenuated the aggressiveness as evidenced by the abolished intensity of aggressive behaviour and increased time of latency before the first attack. The acute trazodone (3--10 mg kg(-1)) or quipazine (1--3 mg kg(-1)) treatment had no or only a minor effect on rat behaviour in the elevated plus-maze, open field, and forced swimming test. Concomitant apomorphine (1 mg kg(-1)) plus trazodone (3 mg kg(-1)), but not apomorphine (1 mg kg(-1)) plus quipazine (1 mg kg(-1)), treatment slowed the development of aggressive behaviour. Repeated apomorphine treatment moderately reduced the dopamine post mortem and increased the DOPAC and HVA contents in striatum. Other monoamines or their metabolites were unchanged. Neither trazodone and quipazine treatment nor forced swimming stress induced any changes in the monoamine contents. In conclusion, our results indicate that acute trazodone and quipazine treatment attenuates the apomorphine-induced aggressive behaviour in male rats, but this phenomenon cannot be implicated in the changes in emotional and motivational behaviour, or in changes of monoamine content post mortem.

Aggression↗

PubMed2001

Apomorphine-induced aggressive behaviour in para-chlorophenylalanine-treated male rats: implications to brain.

The aim of this study was to investigate the role of serotoninergic neurotransmission and the effect of acute para-chlorophenylalanine (350 mg/kg, intraperitoneally) treatment on apomorphine-induced aggressive behaviour in adult male Wistar rats. In addition, [3H]ketanserin binding and monoamine content were studied. Repeated administration of apomorphine (1.0 mg/kg, subcutaneously, once daily for two weeks) gradually induced aggressive behaviour. Acute p-chlorophenylalanine treatment down-regulated the [3H]ketanserin binding and reduced over 90 per cent the content of serotonin and 5-hydroxyindolacetic acid. In a half of the p-chlorophenylalanine-treated animals, the aggressive behaviour was suppressed, while there was no difference in [3H]ketanserin binding or monoamine content between the p-chlorophenylalanine treated aggressive and non-aggressive animals. In conclusion, the acute p-chlorophenylalanine treatment attenuates the aggressiveness only in half of the animals, while the latter phenomenon is independent on the CNS monoamine content or [3H]ketanserin binding.

Aggression↗

PubMed2000

Apomorphine-induced aggressive behaviour and post-mortem monoamine content in male Wistar rats.

The aim of this study was to investigate the monoamine content in post-mortem brain samples of control, apomorphine-aggressive, and apomorphine-non-aggressive adult male Wistar rats. The repeated apomorphine (1.0 mg/kg, (s.c.) once daily during 2 weeks) gradually induced aggressive behaviour in 18 animals out of 24. No unidirectional changes in the brain monoamine contents in four regions (frontal cortex, striatum, hippocampus, and hypothalamus) were detected as measured by high pressure liquid chromatography-electrochemical detection. In conclusion, our present experiment demonstrates that the development and intensity of apomorphine-induced aggressive behaviour do not correlate with the brain post-mortem monoamine content.

Aggression↗

PubMed2000

The serotonin 5-HT(2A) receptor subtype does not mediate apomorphine-induced aggressive behaviour in male Wistar rats.

We have studied the effect of the 5-HT(2A) receptor antagonists on apomorphine-induced aggressive behaviour in male Wistar rats. In acute behavioural experiments with apomorphine-pretreated (1.0 mg/kg, s.c., once daily, 2 weeks) animals, risperidone (0.5 and 1.0 mg/kg) inhibited aggressive behaviour, but ketanserin and ritanserin (0.5-5. 0 mg/kg) had no effect on the latency and intensity of aggressive behaviour. Concomitant risperidone (0.5 mg/kg) and haloperidol (0.03 and 0.3 mg/kg) administration blocked aggressive behaviour completely. In conclusion, our experiments confirm that inhibition of the apomorphine-induced aggressive behaviour is elicited by drugs with dopamine (DA) but not with 5-HT(2A) antagonistic activity. Moreover, it may be concluded that the serotonin 5-HT(2A) receptor subtype does not alter the DA-mediated behaviour.

Aggression↗

PubMed2000

Involvement of GABAergic neurotransmission in the neurobiology of the apomorphine-induced aggressive behavior paradigm, a model of psychotic behavior in rats.

The effect of treatment with the acute GABAA receptor agonist THIP and the GABAB receptor agonist baclofen on apomorphine-induced aggressive behavior was studied in adult male Wistar rats. Both THIP (10 mg/kg i.p.) and baclofen (8 mg/kg i.p.) attenuated the aggressiveness, thereby indicating the involvement of GABAergic neurotransmission in the mediation of apomorphine-induced aggressiveness. On the basis of our data it can be proposed that both GABAA and GABAB receptor subtypes are involved in the neurobiology of apomorphine-induced aggressive behavior, as this phenomenon is evidently subject to the general inhibitory effect of GABAergic neurotransmission.

Aggression↗

PubMed2000

5-HT1A receptor agonists buspirone and gepirone attenuate apomorphine-induced aggressive behaviour in adult male Wistar rats.

We have studied the effects of acute serotonin (5-HT) 5-HT1A receptor agonist buspirone (0.5, 1.0, 2.5 and 5.0 mg/kg, s.c.), gepirone (5.0 and 10 mg/kg, s.c.), and 8-OH-DPAT (0.1, 0.25, and 0.5 mg/kg, i.p.) treatment on the apomorphine-induced aggressive behaviour in adult male Wistar rats. Buspirone in doses of 2.5 and 5.0 mg/kg completely blocked, gepirone (10 mg/kg) significantly attenuated the aggressiveness, and 8-OH-DPAT abolished aggressive behaviour only in the lowest dose used (0.1 mg/kg) which effect disappeared in higher doses. The antiaggressive effect of buspirone (2.5 mg/kg) and gepirone (10 mg/kg) was not reversed by a 5-HT1A receptor antagonist WAY 100635 (0.3 mg/kg). All 5-HT1A receptor agonists tested dose-dependently decreased the exploratory behaviour of experimentally naive rats, while buspirone (2.5 mg/kg) and gepirone (10 mg/kg) had only a weak effect on the locomotor activity and stereotyped behaviour in the apomorphine-pre-sensitised rats. In conclusion, our experiments demonstrate the 5-HTIA receptors may be involved in the mediation of the apomorphine-induced aggressive behaviour in adult male Wistar rats. However, the prominent antiaggressive effect of buspirone, and to a lesser extent--gepirone, seems to be mediated by some other mechanisms, evidently via the dopamine D2 receptors.

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

PubMed1999

Modulatory role of 5-HT3 receptors in mediation of apomorphine-induced aggressive behaviour in male rats.

We have studied the effects of serotonin (5-HT) 5-HT3 receptor agonists 1-phenylbiguanide (1-PBG) and 1-(m-chlorophenyl)biguanide (mCPBG), and antagonists 3-tropanyl-3,5-dichlorobenzoate (MDL-72222) and tropisetron (3-tropanyl-indole-3-carboxylate HCl; ICS-205930) on apomorphine-induced aggressive behaviour in normal or DSP-4 [N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine hydrochloride] pre-treated male Wistar rats. DSP-4 (50 mg/kg) pre-treatment significantly accelerated the development of apomorphine-induced aggressive behaviour. mCPBG (1.0 and 10 mg/kg) did not modify the aggressiveness, but 1-PBG (3.0 and 30 mg/kg) attenuated the aggressiveness in normal but not DSP-4 pre-treated rats. MDL-72222 (0.4 and 4.0 mg/kg) attenuated the aggressive behaviour in normal rats, tropisetron (0.3 mg/kg) had an antiaggressive effect only by citalopram (10 mg/kg) challenge. MDL-72222 and tropisetron were ineffective in DSP-4 pre-treated rats. In conclusion, our results indicate that the 5-HT3 receptors modulate the apomorphine-induced aggressive behaviour and the 5-HT3 receptor antagonists have moderate antiaggressive effect in this test.

Aggression↗

PubMed1999

Acute and chronic citalopram treatment differently modulates rat exploratory behavior in the exploration box test: no evidence for increased anxiety or changes in the [3H]raclopride binding.

The effect of acute and chronic desipramine (10 mg/kg) and citalopram (10 mg/kg) treatment on rat exploratory behavior in the recently developed exploration box test was studied on 5 consecutive days. Acute desipramine but not citalopram treatment decreased the time spent exploring, the number of line crossings, rears, investigative approaches, entries into the large arena, and sum of exploratory events. After 3 weeks of pretreatment, both desipramine and citalopram attenuated rat exploratory behavior, whereas the number of entries into the large arena was unchanged. In the open field test, acute desipramine or citalopram treatment (5, 10, 15 mg/kg) attenuated rat exploratory behavior in a dose-dependent manner. In the subsequent rota-rod test, neither desipramine nor citalopram treatment (0-20 mg/kg) impaired motor performance capacity. In an additional experiment, [3H]raclopride binding was unchanged after single as well as 3 weeks of desipramine or citalopram treatment in the rat brain neostriatum. Our experiments demonstrate that acute citalopram treatment in the open field test and chronic citalopram treatment in the exploration box test attenuate rat exploratory behavior, but these effects may not be implicated with enhanced anxiety or changed dopamine D2 receptor characteristics.

Adrenergic Uptake Inhibitors↗

PubMed1999

Effects of anxiogenic drugs in rat forced swimming test.

The effect of antidepressants and anxiogenics in the forced swimming (Porsolt') test was investigated in rats. On the second day of an experiment, desipramine (10 mg/kg), pentylenetetrazole (20 mg/kg), picrotoxin (2.5 mg/kg), and clonidine (1.0 mg/kg) shortened while buspirone (1.0 mg/kg), yohimbine (2.5 mg/kg), DMCM (1.0 mg/kg), and Ro-15-4513 (1.0 mg/kg) prolonged the time of immobility or behavioral despair; fluoxetine (10 and 20 mg/kg), citalopram (10 mg/kg), and flumazenil (10 mg/kg) were ineffective. While clonidine, given in a subeffective dose (0.1 mg/kg), augmented the effect of desipramine (10 mg/kg), buspirone (1.0 mg/kg) had an opposite effect. The picrotoxin (2.5 mg/kg) challenge prominently shortened the time of immobility after desipramine (10 mg/kg) or citalopram (10 mg/kg) treatment. In conclusion, our results indicate that pharmacologically enhanced anxiety interacts with the effects of acute drug treatment in the forced swimming test.

Animals↗

PubMed1999

Apomorphine-induced upregulation of serotonin 5-HT2A receptors in male rats is independent from development of aggressive behaviour.

The [3H]ketanserin binding characteristics in the apomorphine-induced aggressive and nonaggressive adult male Wistar rats were studied. Repeated apomorphine (0.5 mg/kg, once daily) treatment gradually induced aggressive behaviour in sixteen animals from twenty. Thereafter the animals were retrospectively divided into apomorphine-induced aggressive and nonaggressive group. The maximal number of the [3H]ketanserin binding sites was increased in the apomorphine-treated animals in the frontal (233.9+/-26.5, 364.6+/-31.7, and 367.0+/-34.8 fmol/mg protein for the vehicle, apomorphine-nonaggressive, and apomorphine-aggressive group, respectively) and cerebral cortex (164.2+/-6.7, 289.7+/-29.3, and 249.0+/-15.4 fmol/mg protein for the vehicle, apomorphine-nonaggressive, and apomorphine-aggressive group, respectively). In conclusion, our experiments demonstrate that repeated apomorphine treatment upregulates the maximal number of the 5-HT2A receptors in rat frontal and cerebral cortex as measured by [3H]ketanserin binding and this phenomenon is independent from the development of aggressive behaviour.

Aggression↗

PubMed1999

[3H]-ketanserin binding and elevated plus-maze behavior after chronic antidepressant treatment in DSP-4 and P-CPA pretreated rats: evidence for partial involvement of 5-HT2A receptors.

[3H]-Ketanserin binding in rat neocortex (frontal and cerebral cortex) after 3-week treatment with desipramine (10 mg/kg) and citalopram (5 mg/kg) in vehicle-, DSP-4- (50 mg/kg) and p-CPA- (350 mg/kg before the beginning of experiments and once per week on the first and second week plus 100 mg/kg in the last week) pretreated rats was measured. The antidepressant activity of DSP-4 and p-CPA was evaluated indirectly using the elevated plus-maze test. Acute antidepressant treatment revealed an anxiogenic effect while chronic treatment elicited an anxiolytic effect. DSP-4 and p-CPA pretreatment elicited an antiexploratory effect that was not blocked by acute antidepressant treatment. After 3 weeks of antidepressant treatment, only desipramine + DSP-4 or p-CPA treatment revealed an antiexploratory effect. Three-week antidepressant treatment downregulated [3H]-ketanserin binding in the cerebral cortex. Citalopram treatment partially reversed p-CPA-induced downregulation of [3H]-ketanserin binding in rat whole neocortex. In conclusion, our experiments suggest that the 5-HT2A receptors in monoamine-impaired rats are involved in the mediation of antidepressant-induced behavioral phenomena, but chronic antidepressant treatment downregulates [3H]-ketanserin binding independently from the state of monoaminergic neurotransmission.

Animals↗

PubMed1998

Apomorphine-induced aggressiveness and [3H]citalopram binding after antidepressant treatment in rats.

The effects of acute and repeated administration of antidepressive drugs on apomorphine-induced aggressive behavior and [3H]citalopram binding were studied. In acute behavioral experiments with apomorphine pretreated (1.0 mg/kg, once daily) animals, desipramine (10 mg/kg) and clomipramine (10 mg/kg) enhanced, buspirone (2.5 and 5.0 mg/kg) completely blocked, but fluoxetine, amitriptyline, imipramine (10 mg/kg), and citalopram (10 and 20 mg/kg) had no effect on the intensity of aggressive behavior. Repeated concomitant apomorphine (1.0 mg/kg) and citalopram (10 mg/kg) administration reduced the affinity (Kd) of the 5-HT transporter binding sites in three brain regions. This finding was confirmed by an additional experiment as the effect of citalopram treatment. Repeated apomorphine (1.0 mg/kg) or apomorphine (1.0 mg/kg) plus desipramine (10 mg/kg) treatment had no unidirectional effect on Kd, the maximal number of apparent binding sties (Bmax) was unchanged in all experiments. Our study indicates that the 5-HT reuptake blockade has no major influence on the apomorphine-induced aggressive behavior, but the 5-HT1A receptor subtype may be involved in the mediation of the aggressive behavior in this paradigm.

Aggression↗

PubMed1998

The effect of antidepressants on rat aggressive behavior in the electric footshock and apomorphine-induced aggressiveness paradigms.

The effects of acute antidepressant treatment were studied in the electric footshock and apomorphine-induced aggressiveness paradigms and found to be ineffective in both experimental models. In the apomorphine-induced aggressiveness test, 100 mg/kg L-tryptophan challenge manifested the antiaggressive effect of 10 mg/kg fluoxetine (a selective serotonin reuptake inhibitor) treatment. Thus, concomitant L-tryptophan plus fluoxetine treatment decreased the intensity of aggressive postures and increased the time of latency before first attack. In conclusion, our study demonstrates the involvement of the serotoninergic neurotransmission in the neurobiology of aggressive behavior, but after acute treatment in normal rats, the antidepressants do not elicit antiaggressive effects.

Aggression↗

PubMed1997

Different molecular forms of cholecystokinin and CCKB receptor binding in the rat brain after chronic antidepressant treatment.

Cholecystokinin (CCK) is a neuropeptide recently implicated in affective disorders. This study aimed at measuring the levels of different molecular forms of CCK and the binding characteristics of CCKB receptors in the rat brain after three weeks of treatment with four different antidepressants, imipramine, amitriptyline, desipramine, and citalopram (all at the dose of 10 mg/kg once per day i.p.). Chronic treatment with imipramine and desipramine had a significant immobility-reducing effect in the Porsolt's swim test. The effect of amitriptyline, albeit in the same direction, was not significant, and citalopram had no effect in this test. In the elevated plus-maze test of anxiety, all drugs tended to increase the number of open arm entries and the ratio open/total arm entries, but only the effects of imipramine were statistically significant. None of the treatments affected the total levels of CCK or the levels of CCK-8-sulphated, CCK-8-nonsulphated, CCK-5, or CCK-4 in the frontal cortex. There was no effect of the treatments on CCKB receptor binding in the frontal cortex, hippocampus, or striatum. Imipramine and amitriptyline, however, increased the affinity of CCKB receptor binding in the hypothalamus. Thus, no consistent effect of chronic antidepressant treatment on the CCK-ergic neurotransmission in the rats was found.

Animals↗

PubMed1997

The effects of cholecystokinin A and B receptor antagonists on exploratory behaviour in the elevated zero-maze in rat.

The aim of the present study was to investigate the effects of cholecystokinin (CCK) CCK(A) and CCKB receptor antagonists SR 27897 B, devazepide, L 365260 and PD 135158 (CAM 1028) on exploratory behaviour in the elevated zero-maze in the rat. For further validation of the elevated zero-maze, the effects of a reference anxiolytic diazepam (0.25, 0.5, 1.0, 2.0 mg/kg), a non-benzodiazepine (BDZ) anxiolytic buspirone (0.04, 0.2, 1.0, 5.0 mg/kg), BDZ receptor inverse agonists FG 7142 (5, 10, 15, 20 mg/kg) and DMCM (0.1, 0.5, 1.0, 1.5 mg/kg), and a BDZ receptor antagonist flumazenil (10 mg/kg) were studied. Diazepam decreased the number of stretched-attend postures in all doses used and increased the percentage of time spent exploring in open parts at doses of 0.5 and 1.0 mg/kg. The effects of diazepam were blocked by flumazenil. FG 7142 and DMCM had effects only in subconvulsive doses (20 mg/kg and 1.5 mg/kg). Flumazenil and buspirone failed to show any effect. The CCK(A) receptor antagonists were also without any effect. The CCK(B) receptor antagonists L 365260 (1.0 and 5.0 mg/kg) and PD 135158 (100 microg/kg) had a significant anxiolytic-like effect. The CCK(B) receptor antagonists increased the number of open part entries, the number of head dips, the percentage of time spent exploring in the open part and decreased the number of stretched-attend postures. These data support the hypothesis of the involvement of the CCK(B) receptor subtype in the neurobiological mechanisms of anxiety.

Animals↗

PubMed1997

The effect of drugs acting on CCK receptors and rat free exploration in the exploration box.

The effects of cholecystokinin (CCK) CCKA receptor antagonist devazepide (10 micrograms/kg and 1.0 mg/kg), CCKB receptor antagonist L 365260 (1.0 mg/kg), and CCKB receptor agonist CCK tetrapeptide (CCK-4, 75 micrograms/kg), and their concomitant administration with antidepressants desipramine (10 mg/kg) and citalopram (10 mg/kg) on rat exploratory behaviour were studied in the recently developed exploration box test. In addition, the effects of repeated administration of despiramine (10 mg/kg) and citalopram (10 mg/kg) were studied. After acute administration, CCK-4 decreased significantly the number of line crossings, rears, investigative approaches, and the time spent exploring. The time of latency and the number of entries into large arena were unchanged. Desipramine reduced all observed criterions of rat behaviour, but citalopram was ineffective. Devazepide (1.0 mg/kg) and L 365260 (1.0 mg/kg) had no effect on rat behaviour after acute or repeated administration. L 365260 (1.0 mg/kg) blocked the antiexploratory effect of CCK-4, whereas devazepide (10 micrograms/kg) did not. No interaction of CCK-4, devazepide, or L 365260 treatment with antidepressant treatment was found. Our results suggest that the administration of a CCKB agonist diminishes rat exploratory behaviour, but neither CCKA nor CCKB receptor blockade induces changes on rat exploratory behaviour in the free exploration paradigm.

Adrenergic Uptake Inhibitors↗