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L Allikmets

Publications and source records attributed to L Allikmets.

31 records · Page 2Linked to original sources

Characterization of rat exploratory behavior using the exploration box test.

A method to measure various aspects of exploratory behavior was further characterized using standard pharmacological treatments known to induce anxiety, or anxiolysis, or locomotor activation. FG 7142, an anxiogenic beta-carboline, induced a dose-dependent reduction in the rat exploratory behavior. A single FG 7142 (20 mg/kg) treatment before behavioral testing had a carry-over effect on rats' behavioral performance on the two subsequent days. When FG 7142 (20 mg/kg) was administered during five consecutive days before behavioral testing, its anxiogenic-like effect first deepened, but waned off by the fifth session. Diazepam at the dose of 0.5 mg/kg had no effect of its own, but blocked the anxiogenic-like effect of FG 7142 (10 mg/kg) treatment. At a higher dose (1 mg/kg), diazepam treatment reduced exploratory behavior, but this effect was not carried over to the drug-free sessions on the subsequent day. Buspirone and gepirone (both 1 mg/kg), the 5-HT1A receptor agonists, had no effect. D-Amphetamine, a locomotion-enhancing drug which has anxiogenic-like properties in several tests of exploratory behavior, increased the activity of rats at the dose of 0.5 mg/kg, but at the dose of 1 mg/kg the only effect was a reduction in the number of rearings: this effect was not carried over to the subsequent retest. On the basis of the results described in this article and elsewhere, we suggest that this technique can be useful for separating a true anxiogenic drug from other compounds which influence exploratory activity.

Amphetamine↗

The effects of cholecystokinin A and B receptor antagonists, devazepide and L 365260, on citalopram-induced decrease of exploratory behaviour in rat.

The present study has been divided into two sets. In the first set, the aim of the experiments was to investigate the dose-response effect of selective serotonin re-uptake inhibitor (SSRI) citalopram on rat exploratory behaviour in the elevated plus-maze. In the second set of experiments, the effect of cholecystokinin (CCK) CCKA and CCKB receptor antagonists, devazepide and L 365260, on citalopram-induced decrease of exploratory behaviour in the elevated plus-maze was studied. Citalopram (5 and 10 mg/kg) decreased the number of open and total arm entries, line crossings on open arms, and percentage of time spent exploring in open arm. Dose 15 mg/kg was without any effect on rat exploratory behaviour. Devazepide (0.01 and 1.0 mg/kg) failed to modify any of the citalopram-induced changes observed. L 365260 (1.0 mg/kg) reversed most of the effects of citalopram: the numbers of open and total arm entries, the number of line crossings, and the percentage of time spent exploring in open arms. L 365260 at dose level 0.01 mg/kg was ineffective. These results support the involvement of the CCKB receptor subtype in SSRI-induced anxiogenic-like effects in rodents.

Animals↗

Possibilities for future cooperation within the field of respiratory physiology and pharmacology.

From the viewpoint of clinical research in respiratory diseases the situation seems promising. On one hand, there are a lot of unanswered questions in pulmonology. And on the other, there are possibilities to solve these questions, by the combination of research experience, facilities, patients, and last but not least--individual initiatives. Shortage of money has the positive effect in maintaining the simple and reliable old skills in research and clinical practice as there are few sophisticated and expensive apparatus to rely on. The physicians must also be very inventive to help their patients when medical supplies are insufficient. Therefore, success in science and in scientific cooperation is determined by the persons engaged. Finding capable and dedicated people is crucial and the most vital challenge to whatever project. And such people can be found on both sides of the Baltic Sea. In conclusion, this short description of differences between the Baltic States and the Nordic countries could, give some clues for future cooperation. Based on the well known key-lock model of pharmacology, team-work between different talents will give results not attainable individually. When all think alike, nobody thinks.

Animals↗

Similar behavioral and biochemical effects of long-term haloperidol and caerulein treatment in albino mice.

Behavioral and biochemical experiments on male albino mice have revealed similar effects after the cessation of repeated (15 days) haloperidol (0.5 mg/kg daily IP) and caerulein (0.1 mg/kg daily SC) treatment. Tolerance developed to the action of muscimol (a GABA-A agonist, 1 mg/kg IP), caerulein (a CCK-8 agonist, 15 micrograms/kg SC) and flumazenil (a benzodiazepine antagonist, 10 mg/kg IP). Muscimol and caerulein were not able to suppress the motor activity of mice after 15 days treatment with haloperidol and caerulein. Flumazenil, which increased motor activity in saline-treated animals, also failed to affect activity after extended haloperidol or caerulein treatment. In contrast, the motor excitation induced by amphetamine (an indirect dopamine agonist, 3 mg/kg IP) was increased after haloperidol or caerulein administration. In radioligand binding studies the density of dopamine-2-receptors in striatum, opioid receptors in mesolimbic structures, and benzodiazepine and GABA-A receptors in brainstem was significantly elevated after long-term haloperidol or caerulein treatment. Simultaneously, the number of CCK-8, benzodiazepine and GABA-A receptors in cerebral cortex was decreased. It is probable that CCK-8-ergic mechanisms are involved closely in the action of repeated haloperidol treatment. CCK-8 seems to modulate the action of haloperidol through altering the sensitivity of dopamine, opioid, GABA-A and benzodiazepine receptors.

Amphetamine↗

Stress-protection action of beta-phenyl(GABA): involvement of central and peripheral type benzodiazepine binding sites.

Forced swimming stress caused a significant increase in the density of central type benzodiazepine binding sites in rat cerebral cortex and hippocampus. The number of peripheral type benzodiazepine binding sites was also enhanced on blood platelets. The affinity of neither central nor peripheral type benzodiazepine binding sites was changed considerably after swimming stress. Pretreatment of rats with beta-(phenyl)GABA (100 mg/kg), a GABAB agonist, almost completely eliminated the described changes of the both types of benzodiazepine binding sites caused by swimming stress. In an elevated plus-maze model of anxiety beta-(phenyl)GABA itself was inactive but like diazepam effectively counteracted the behavioural effects of DMCM, a beta-carboline derivative with anxiogenic properties. The possible involvement of benzodiazepine receptors in the mechanism of action of beta-(phenyl)GABA is discussed.

Animals↗

Comparison of motor depressant effects of caerulein and N-propylnorapomorphine in mice.

The motor depressant effects of caerulein and N-propylnorapomorphine (NPA) were compared in male mice. Caerulein (1-50 micrograms/kg SC) in a dose dependent manner depressed the exploratory activity, whereas NPA in lower doses (0.5-10 micrograms/kg SC) decreased the motor activity, but in higher doses (over 50 micrograms/kg) had stimulating effect on the exploratory behavior. In mice selected according to their motor response after administration of 100 micrograms/kg NPA to weak and strong responders, the low dose of NPA (1 microgram/kg) similarly suppressed motor activity in both selected groups, while the effect of caerulein (2 micrograms/kg) was apparently higher in weak responders. Destruction of catecholaminergic terminals by 6-hydroxydopamine (60 micrograms ICV) reversed completely the motor depressant effect of NPA, whereas degeneration of serotoninergic terminals (5,7-dihydroxytryptamine 60 micrograms ICV or p-chloroamphetamine 2 X 15 mg/kg IP) enhanced the sedative effect of NPA. The motor depressant effect of caerulein remained unchanged after lesions of monoaminergic terminals in forebrain. Subchronic haloperidol (0.25 mg/kg IP, twice daily during 14 days) treatment, reducing significantly the density of high-affinity dopamine2- and serotonin2-receptors, decreased the motor depressant action of caerulein. It is possible that motor depressant effect of caerulein, differently from the action of NPA, is mediated through the high-affinity dopamine2-receptors and in lesser extent through the high-affinity serotonin2-receptors.

5,7-Dihydroxytryptamine↗

Additive effect of clonidine and fluoxetine on apomorphine-induced aggressive behavior in adult male Wistar rats.

BACKGROUND: Fluoxetine, a selective serotonin reuptake inhibitor, has been reported to be superior in its antiaggressive properties as compared with other antidepressants. The objective of the study was to investigate whether the effect of a minimal effective dose of fluoxetine could be potentiated by the alpha2-adrenergic agonist clonidine. METHODS: Vehicle (1.0 mL/kg), clonidine (0.1 mg/kg), fluoxetine (10 mg/kg), and their combination [clonidine (0.1 mg/kg) plus fluoxetine (10 mg/kg)] were injected into apomorphine-pretreated (1.0 mg/kg, once daily during 12 days) aggressive adult male Wistar rats. RESULTS: Repeated apomorphine treatment induced a gradual development of aggressive behavior. Combined clonidine and fluoxetine treatment attenuated the intensity of aggressive behavior, while these drugs alone had only a weak tendency toward reduction of aggression. Latency before the first attack was unchanged. CONCLUSIONS: Our experiments confirm that combined clonidine and fluoxetine treatment elicits an additive antiaggressive effect on apomorphine-induced aggressive behavior in rats.

Adrenergic alpha-Agonists↗

Development of apomorphine-induced aggressive behavior: comparison of adult male and female Wistar rats.

The development of apomorphine-induced (1.0 mg/kg s.c. once daily) aggressive behavior of adult male and female Wistar rats obtained from the same breeder was studied in two consecutive sets. In male animals, repeated apomorphine treatment induced a gradual development of aggressive behavior as evidenced by the increased intensity of aggressiveness and shortened latency before the first attack toward the opponent. In female rats, only a weak tendency toward aggressiveness was found. In conclusion, the present study demonstrates gender differences in the development of the apomorphine-induced aggressive behavior and indicates that the female rats do not fill the validation criteria for use in this method.

Aggression↗

Changes in [3H]citalopram binding in cerebral cortex after antidepressant treatment in monoamine-impaired rats.

The [3H]citalopram binding after three weeks vehicle, desipramine 10 mg/kg or citalopram 5 mg/kg treatment was studied in the cerebral cortex of normal, DSP-4-, and p-CPA-impaired rats. The DSP-4 50 mg/kg treatment decreased the affinity (Kd), but increased the maximal number of the apparent binding sites (Bmax) of the 5-hydroxytryptamine transporter (5-HTT). This effect was reversed by desipramine 10 mg/kg treatment. The p-CPA 350 mg/kg treatment decreased the Bmax value while the antidepressant treatment did not influence this parameter. In conclusion, our experiments demonstrate that the monoaminergic impairment induced by DSP-4 and p-CPA treatment evokes opposite changes in the 5-HTT binding characteristics and these changes are partially reversed by the chronic antidepressant treatment.

Animals↗