Actions of Novel Antipsychotic Agents on Apomorphine-Induced PPI Disruption: Influence of Combined Serotonin 5-HT1A Receptor Activation and Dopamine D2 Receptor Blockade

Auclair, Agnès; Kleven, Mark S.; Besnard, Joël; Depoortère, R.; Newman‐Tancredi, Adrian

doi:10.1038/sj.npp.1301015

Cited by 60 publications

(48 citation statements)

References 62 publications

(75 reference statements)

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“…Moreover, aripiprazole (10 and 30 mg / kg) improved the disruption of the PPI induced by apomorphine and DOI dose-dependently. The effect of aripiprazole on the PPI disruption induced by apomorphine was previously reported by other researchers (13). In their investigation, not only high dose of aripiprazole (10 mg / kg), but also Fig.…”

Section: Discussionmentioning

confidence: 65%

Effect of Aripiprazole on 5-HT2 Receptor–mediated Wet-Dog Shake Responses and Disruption of Prepulse Inhibition in Rats

et al. 2008

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Abstract. Aripiprazole, an atypical antipsychotic drug, is a D 2 dopamine-receptor partial agonist, but also has affinity to several serotonin receptors (5-HT 1A,2A,2C,7 ). However, little is known about the contribution of serotonin receptors in the action of aripiprazole. The present study investigated the effects of aripiprazole on 5-HT 2A receptor-mediated behaviors and compared them with the effects on dopamine receptor-mediated behavior in rats. Aripiprazole (10, 30 mg/ kg, p.o.) inhibited the stereotyped behavior induced by apomorphine (1 mg / kg, s.c.), a dopamine-receptor agonist, and the wet-dog shake responses induced by DOI (2,5-dimethoxy-4-iodoamphetamine, 2 mg / kg, s.c.), a 5-HT 2A -receptor agonist. Moreover, aripiprazole improved the disruption of prepulse inhibition induced by both apomorphine and DOI significantly. These data suggest that not only the dopaminergic system, but also the serotonergic system are involved in the antipsychotic effect of aripiprazole.

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Section: Discussionmentioning

confidence: 65%

Effect of Aripiprazole on 5-HT2 Receptor–mediated Wet-Dog Shake Responses and Disruption of Prepulse Inhibition in Rats

et al. 2008

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“…Of the antipsychotics we also included, pretreatment with haloperidol, risperidone, and olanzapine blocked the effect of apomorphine, whereas clozapine and aripiprazole were less effective (Auclair et al, 2006). Interestingly, when pretreatment with mixed D 2 /5-HT 1A ligands was combined with a 5-HT 1A receptor antagonist, the ability to block the action of apomorphine was enhanced.…”

Section: Discussionmentioning

confidence: 99%

“…In a recent study, several antipsychotics were tested against the disruption of PPI induced by treatment with the dopamine receptor agonist, apomorphine (Auclair et al, 2006). Of the antipsychotics we also included, pretreatment with haloperidol, risperidone, and olanzapine blocked the effect of apomorphine, whereas clozapine and aripiprazole were less effective (Auclair et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

Differential Effects of Antipsychotic Drugs on Serotonin-1A Receptor-Mediated Disruption of Prepulse Inhibition

Buuse¹,

Gogos²

2006

J Pharmacol Exp Ther

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Serotonin-1A (5-HT 1A ) receptors have been implicated in the symptoms of schizophrenia. However, there is limited in vivo evidence for an interaction of antipsychotic drugs with 5-HT 1A receptor-mediated behavioral effects. We therefore investigated in rats the action of several antipsychotic drugs on prepulse inhibition (PPI), a measure of sensorimotor gating that is deficient in schizophrenia. Disruption of PPI at the 100-ms interstimulus interval (ISI), but not the 30-ms ISI, was induced by treatment with 0.5 mg/kg 8-hydroxy-di-propylaminotetralin

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“…Apomorphine-induced PPI deficits can be reversed by haloperidol (Auclair et al, 2006). Some reports describe reversal of apomorphine-induced PPI deficits by clozapine, although its effects are often limited to a narrow dose range (Martin et al, 2003).…”

Section: Attentional Processesmentioning

confidence: 99%

Behavioral Indices in Antipsychotic Drug Discovery

Porsolt

Moser²,

Castagné³

2010

J Pharmacol Exp Ther

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Schizophrenia is characterized by three major symptom classes: positive symptoms, negative symptoms, and cognitive deficits. Classical antipsychotics (phenothiazines, thioxanthenes, and butyrophenones) are effective against positive symptoms but induce major side effects, in particular, extrapyramidal symptoms (EPS). The discovery of clozapine, which does not induce EPS and is thought effective against all three classes of symptom, has driven research for novel antipsychotics with a wider activity spectrum and lower EPS liability. To increase predictiveness, current efforts aim to develop translational models where direct parallels can be drawn between the processes studied in animals and in humans. The present article reviews existing procedures in animals for their ability to predict compound efficacy and EPS liability in relation to their translational validity. Rodent models of positive symptoms include procedures related to dysfunction in central dopamine and glutamatergic (N-methyl-D-aspartate) and serotonin (5-hydroxytryptamine) neurotransmission. Procedures for evaluating negative symptoms include rodent models of anhedonia, affective flattening, and diminished social interaction. Cognitive deficits can be assessed in rodent models of attention (prepulse inhibition) and of learning/memory (object and social recognition, Morris water maze and operant-delayed alternation). The relevance of the conditioned avoidance response is also discussed. A final section reviews procedures for assessing EPS liability, in particular, parkinsonism (catalepsy in rodents), acute dystonia (purposeless chewing in rodents, dystonia in monkeys), akathisia (defecation in rodents), and tardive dyskinesia (long-term antipsychotic treatment in rodents and monkeys). It is concluded that, with notable exceptions (attention, learning/ memory, EPS liability), current predictive models for antipsychotics fall short of clear translational validity.Schizophrenia is characterized by three major classes of symptom: positive symptoms (delusions, hallucinations, bizarre speech and thought, paranoia); negative symptoms (anhedonia, affective flattening, impoverishment of speech and thought, social withdrawal); and cognitive deficits (impairments in attention, learning, and memory).Despite intensive research, the etiology of schizophrenia remains far from understood. Most hypotheses have evolved from the actions of drugs in clinical use or as a result of similarities between the symptoms of schizophrenia and the effects of certain drugs of abuse, notably the indirect dopamine (DA) receptor agonist amphetamine, the glutamate receptor antagonist phencyclidine (PCP), and the 5-HT 2 receptor agonist lysergic acid diethylamide. The major hypothesis has centered around central DA neurotransmission because all classical antipsychotics (phenothiazines, thioxanthenes, and butyrophenones) have as principal mechanism the blockade of central DA receptors (Carlsson, 1988).The introduction of the atypical antipsychotic clozapine in the early 1970s an...

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Actions of Novel Antipsychotic Agents on Apomorphine-Induced PPI Disruption: Influence of Combined Serotonin 5-HT1A Receptor Activation and Dopamine D2 Receptor Blockade

Cited by 60 publications

References 62 publications

Effect of Aripiprazole on 5-HT2 Receptor–mediated Wet-Dog Shake Responses and Disruption of Prepulse Inhibition in Rats

Effect of Aripiprazole on 5-HT2 Receptor–mediated Wet-Dog Shake Responses and Disruption of Prepulse Inhibition in Rats

Differential Effects of Antipsychotic Drugs on Serotonin-1A Receptor-Mediated Disruption of Prepulse Inhibition

Behavioral Indices in Antipsychotic Drug Discovery

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