Apomorphine-induced Aggressive Behaviour Research Articles

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 α2-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.

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.

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.

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.

Role of serotonin and serotonin receptors in the apomorphine-induced aggressive behaviour of adult male Wistar rats

Role of serotonin and serotonin receptors in the apomorphine-induced aggressive behaviour of adult male Wistar rats

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.

Modulatory role of 5-HT 3 receptors in mediation of apomorphine-induced aggressive behaviour in male rats

We have studied the effects of serotonin (5-HT) 5-HT 3 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-HT 3 receptors modulate the apomorphine-induced aggressive behaviour and the 5-HT 3 receptor antagonists have moderate antiaggressive effect in this test.

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 ( K d) 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 K d, the maximal number of apparent binding sties ( B max) 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-HT 1A receptor subtype may be involved in the mediation of the aggressive behavior in this paradigm.

6-(alkylamino)-9-alkylpurines. A new class of potential antipsychotic agents.

A series of 6-(alkylamino)-9-alkylpurines was synthesized and evaluated for the property of antagonizing the behavioral effects in animals of the dopamine agonist apomorphine. This model for identifying potential antipsychotic agents is based on the hypothesis that agents that antagonize apomorphine-induced aggressive behavior in rats and apomorphine-induced climbing in mice, but that do not block stereotyped behavior, could have an antipsychotic effect in humans without producing extrapyramidal side effects. The antiaggressive-behavior activity of lead compound 1 (6-(dimethylamino)-9-(3-phenylalaninamidobenzyl)-9H-purine) was improved 48-fold with 6-(cyclopropylamino)-9-(cyclopropylmethyl)-2-(trifluoromethyl)-9H- purine (80) (po ED50 of 2 mg/kg), which was obtained through an iterative sequence of structure--activity relationship studies that encompassed evaluation of the effects of structure variations at the purine 9-, 6-, and 2-positions. Potency was enhanced with a 9-cyclopropyl group, the duration of action was improved with the 6-(cyclopropylamino) substituent, potency was further enhanced with an N-formyl prodrug, and an agent with reduced cardiovascular effect emerged with the 2-trifluoromethyl purine 80. This potential antipsychotic agent was not developed further due to undesirable effects on the stomach.

Role of N-methyl-D-aspartic acid and cholecystokinin receptors in apomorphine-induced aggressive behaviour in rats.

We studied the aggressive behaviour induced by repeated treatment with apomorphine, a dopamine agonist (0.5 mg/kg s.c. twice daily, 10 days), in rats. The first signs of defensive aggressiveness appeared on the third day of apomorphine treatment and were generally seen on the 7th day. Aggressiveness induced by a challenge dose of apomorphine (0.5 mg/kg s.c.) on the 11th day was antagonized by haloperidol (0.05 and 0.1 mg/kg i.p.) and clozapine (10 mg/kg i.p.). An antagonist of N-methyl-D-aspartate (NMDA)-gated channels, dizocilpine (MK-801), also blocked the aggressive behaviour at 0.25 and 0.5 mg/kg i.p. but caused ataxia. When dizocilpine (0.25 mg/kg i.p.) and apomorphine were coadministered for 10 days, aggressive behaviour did not develop. At 0.025 mg/kg i.p., dizocilpine even accelerated the appearance of apomorphine-induced aggressive behaviour, which manifested on the 3rd day in all rats. In a separate study, a 7-day treatment with dizocilpine (0.25-1 mg/kg i.p.) of rats, sensitized by a prior 10-day apomorphine treatment, did not reverse the established aggressive behaviour. The coadministration of apomorphine and cholecystokinin (CCK) -A or -B antagonists, devazepide or L-365,260 (0.01-2.5 mg/kg i.p.) respectively, neither affected development of apomorphine-induced aggressive behaviour nor intensity of aggressiveness in the sensitized rats. In binding studies neither density nor affinity of striatal dopamine D2 receptors was changed by acute or chronic apomorphine treatment. The number of [3H]pCCK-8 binding sites in the frontal cortex increased already after a single injection of apomorphine.(ABSTRACT TRUNCATED AT 250 WORDS)

Chronic treatment with antidepressant drugs: Potentiation of apomorphine-induced aggressive behaviour in rats

Chronic (14 days) but not acute treatment with antidepressants (amitriptyline, imipramine, desipramine, clomipramine, mianserin, danitracen, iprindole) potentiated the aggressive behaviour induced by apomorphine (APO) in rats. The APO stereotypy was not changed. A similar potentiation was caused by chronic treatment with phentolamine or thioridazine but not with spiperone or diazepam. In rats treated chronically with amitriptyline the APO-induced fighting was antagonized by phenoxybenzamine or spiperone, and not by metergoline. The results allow us to postulate that the chronic treatment with antidepressants potentiates the APO-induced aggressiveness via the noradrenergic mechanism, i.e., through an enhanced response to the endogenous NA.

Tentative analysis of apomorphine-induced intraspecific aggressive behavior in the rat according to Adams's classification

Tentative analysis of apomorphine-induced intraspecific aggressive behavior in the rat according to Adams's classification

Effets de l�sions de l'hypothalamus et du globus pallidus et d'injections d'apomorphine dans le globus pallidus, le noyau caud�, la substantia nigra et le septum sur le ?comportement d'agressivit� induit par l'apomorphine? chez le rat

Intraspecific apomorphine-induced aggressive behavior in the rat was not affected following electrolytic lesions of the ventromedial hypothalamus. Some inhibition of the aggressive behavior was found after lateral lesions and an almost total suppression after destruction of globus pallidus. These results, as well as those following localized injections of apomorphine into the septum, substantia nigra, caudate nucleus, and globus pallidus suggested that the latter anatomical region may be the major site of the action of apomorphine in the behavior studies. The role of acetylcholine is discussed.

Apomorphine-induced aggression in the rat

Summary Spontaneous aggression in male rats was observed following injections of apomorphine, 10–30 mg/kg subcutaneously. The aggressive response could be elicited following smaller doses of apomorphine, 5–10 mg/kg, by pinching the tail 30 min after apomorphine treatment. The occurrence of spontaneous fighting and pain-induced fighting following apomorphine depended upon the age of the animals. Aggression was not observed until animals had attained the age of 49–56 days. Pretreatment with reserpine lowered the threshold for induction of aggressive responses by apomorphine. With reserpine pretreatment, spontaneous aggression was observed following apomorphine in doses of 0.5–2.5 mg/kg subcutaneously. If one assumes that apomorphine is a specific agonist at dopaminergic receptors, then these results suggest that the apomorphine-induced aggressive behaviour as well as the similar mock-fighting behaviour following l -DOPA or dexamphetamine, as reported by other authors, is probably a consequence of enhanced activity at dopaminergic receptors.