Ruth Rudissaar

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.

The serotonin 5-HT2A receptor subtype does not mediate apomorphine-induced aggressive behaviour in male Wistar rats

We have studied the effect of the 5-HT2A 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-HT2A antagonistic activity. Moreover, it may be concluded that the serotonin 5-HT2A receptor subtype does not alter the DA-mediated behaviour.

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.

Role of 5-HT1A receptors in the mediation of acute citalopram effects: a 8-OH-DPAT challenge study.

(1) The study was aimed to investigate the effects of the minimal effective doses of acute citalopram (5 mg/kg), (+/-)-8-hydroxydipropylaminotetralin HBr (8-OH-DPAT; 0.1 mg/kg), and their combined treatment on the rat open field and forced swimming behaviour and post-mortem monoamine content. (2) The animals were prospectively divided into the vehicle- and para-chlorophenylalanine (p-CPA)-pretreated (350 mg/kg) groups. (3) Acute citalopram (5 mg/kg), 8-OH-DPAT (0.1 mg/kg), or their combined treatment had no major effect on the rat open field and forced swimming behaviour. (4) The post-mortem catecholamine content in four brain regions studied was unchanged in all treatment groups. (5) The combined 8-OH-DPAT (0.1 mg/kg) and citalopram (5 mg/kg) treatment partially reversed the p-CPA-induced decrease of serotonin (5-HT) and 5-hydroxy-indolacetic acid (5-HIAA) content. (6) The present experiments demonstrate that the 5-HT1A receptors mediate some of the selective serotonin reuptake inhibitor (SSRI)-induced biochemical phenomena.