Showing papers by "Eero Vasar published in 1994"

Opposite effects mediated by CCKA and CCKB receptors in behavioural and hormonal studies in rats.

Abstract: We compared the influence of two cholecystokinin (CCK) antagonists, devazepide and L,365,260 [3R-(+)-(2,3-dihydro-1-methyl-2-oxo-5-phenyl-1 H-1,4-benzodiazepine-3y1)-N′-(3-methyl-phenyl)urea], upon two distinct phenomena, behavioural and hormonal effects of caerulein (5 μg/kg s.c.), and unselective CCK agonist, in rats. Behavioural effects were assessed in the elevated plusmaze and open field tests. In separate experiments, effects on thyrotropin (TSH), prolactin (PRL) and growth hormone (GH) levels in serum of male rats were studied. Caerulein inhibited the exploratory behaviour in the plus-maze. Time spent in the open part, the number of line crossings and closed arm entries were significantly decreased, whereas the ratio of failed attempts/closed arm entries was increased. The anti-exploratory effect of caerulein was antagonized by the pretreatment with L-365,260 (10 μg/kg), a preferential antagonist at CCKB receptors, but was increased by devazepide (1–100 μg/kg), a preferential CCKA antagonist. L-365,260 (1–100 ⧎/kg) and devazepide (1–100 Fig/kg) given alone did not change the behaviour of rats in the plusmaze test. Caerulein (5 μg/kg) itself did not modify the locomotor activity of rats in open field. However, the concomitant administration of caerulein with devazepide (1–10 μg/kg) reduced the frequency of line crossings and rearings. In the hormonal studies caerulein significantly decreased the cold-induced increase of TSH levels in serum. GH and PRL levels were not markedly affected by caerulein. Pretreatment with devazepide (100 μg/kg) antagonized, while Lr365,260 (100 Ng/kg) even increased, the suppressing effect of caerulein on TSH levels. The concomitant administration of L-365,260 and caerulein reduced the levels of GH, whereas the combination of CCK agonist with devazepide caused the opposite effect. L-365,260 and devazepide alone did not change the levels of hormones in serum. The results support the idea that CCKA and CCKB receptors exert an opposite influence not only upon the exploratory behaviour in rats (CCKA receptor activation mediates an increase, CCKB receptor activation a decrease) but also upon the secretion of two anterior pituitary hormones, TSH and probably GH (CCKA receptor activation mediates a decrease, CCKB receptor activation an increase).

Pharmacological Comparison of Antipsychotic Drugs and σ-Antagonists in Rodents

Abstract: We compared antipsychotic drugs (haloperidol, chlorpromazine and clozapine) and sigma antagonists (remoxipride, cinuperone, alpha-(4-fluorophenyl)-4-(-fluoro-2-pyrimidinyl)-1-piperazine butanol (BMY 14802) and rimcazole) in the radio-ligand binding and behavioural experiments in rodents. A good correlation was established between the affinity of compounds at dopamine2-receptors in the striatum and their ability to block apomorphine-, amphetamine- and quipazine-induced behavioural effects in rodents. By contrast, no correlation was found between the behavioural effects of these drugs and their affinity at dopamine1-5-HT2- and sigma receptors. The rank order of potency among the studied antipsychotic drugs in the behavioural tests and at dopamine2-receptors was following: haloperidol >> chlorpromazine > or = clozapine. The effectiveness of chlorpromazine and clozapine was nearly similar against apomorphine-induced aggressiveness and yawning, whereas at 5-HT2-receptors clozapine was more active than chlorpromazine. The weak activity of sigma antagonists at dopamine2 receptors could be a possible reason why these compounds were less effective in the behavioural studies compared to antipsychotic drugs. However, the antagonism of remoxipride against apomorphine-induced stereotypy and aggressiveness is not related to its activity at sigma receptors, because the other sigma antagonists did not block these effects of apomorphine. It is probable that remoxipride exerts its action through blocking of dopamine2 receptors. In conclusion, the present study revealed only weak activity of sigma antagonists in the behavioural models widely used to study the antipsychotic drugs. Therefore, the antipsychotic activity of sigma antagonists is doubtful.