Dose determination of haloperidol, risperidone and olanzapine using an in vivo dopamine D2-receptor occupancy method in the rat

Naiker, Dineshree; Catts, Stanley V.; Catts, Vibeke S.; Bedi, K. S.; Bryan-Lluka, Lesley J.

doi:10.1016/j.ejphar.2006.04.048

Cited by 24 publications

(22 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A 0.75 mg/kg aripiprazole dosage in rats is equivalent to ~7.5 mg in humans (60 kg body weight), while 0.8 mg/kg bifeprunox and 0.1 mg/kg haloperidol is equivalent to ~8 mg and ~1 mg respectively, all of which are within the used/recommended clinical dosages (Casey et al, 2008, Emsley, 2009, Mace and Taylor, 2009. It was reported that aripiprazole and bifeprunox, at these dosages, had over 90% D 2 receptor occupancy in rat brains (Wadenberg, 2007), while haloperidol reached approximately 70% D 2 R occupancy , Naiker et al, 2006, Natesan et al, 2006. Furthermore, the dosages used in this study have been shown to be physiologically and behaviourally effective in rodents (Assie et al, 2006, De Santis et al, 2014, Han et al, 2009, Kesby et al, 2006, Wadenberg, 2007, whilst not causing EPS side-effects (Natesan et al, 2006, Wadenberg, 2007.…”

Section: Animals and Drug Administrationmentioning

confidence: 84%

Aripiprazole Increases the PKA Signalling and Expression of the GABAA Receptor and CREB1 in the Nucleus Accumbens of Rats

et al. 2016

View full text Add to dashboard Cite

The GABAA receptor is implicated in the pathophysiology of schizophrenia and regulated by PKA signalling. Current antipsychotics bind with D2-like receptors, but not the GABAA receptor. The cAMP-responsive element-binding protein 1 (CREB1) is also associated with PKA signalling and may be related to the positive symptoms of schizophrenia. This study investigated the effects of antipsychotics in modulating D2-mediated PKA signalling and its downstream GABAA receptors and CREB1. Rats were treated orally with aripiprazole (0.75 mg/kg, ter in die (t.i.d.)), bifeprunox (0.8 mg/kg, t.i.d.), haloperidol (0.1 mg/kg, t.i.d.) or vehicle for 1 week. The levels of PKA-Cα and p-PKA in the prefrontal cortex (PFC), nucleus accumbens (NAc) and caudate putamen (CPu) were detected by Western blots. The mRNA levels of Gabrb1, Gabrb2, Gabrb3 and Creb1, and their protein expression were measured by qRT-PCR and Western blots, respectively. Aripiprazole elevated the levels of p-PKA and the ratio of p-PKA/PKA in the NAc, but not the PFC and CPu. Correlated with this elevated PKA signalling, aripiprazole elevated the mRNA and protein expression of the GABAA (β-1) receptor and CREB1 in the NAc. While haloperidol elevated the levels of p-PKA and the ratio of p-PKA/PKA in both NAc and CPu, it only tended to increase the expression of the GABAA (β-1) receptor and CREB1 in the NAc, but not the CPu. Bifeprunox had no effects on PKA signalling in these brain regions. These results suggest that aripiprazole has selective effects on upregulating the GABAA (β-1) receptor and CREB1 in the NAc, probably via activating PKA signalling.

show abstract

Section: Animals and Drug Administrationmentioning

confidence: 84%

Aripiprazole Increases the PKA Signalling and Expression of the GABAA Receptor and CREB1 in the Nucleus Accumbens of Rats

et al. 2016

View full text Add to dashboard Cite

show abstract

“…The dose of risperidone used in our study was relatively low. This probably resulted in a relatively low rate of spatial impairment during the task, since D2-receptor occupancy is achieved with risperidone at 5mg/kg/day (Naiker et al, 2006. Risperidone, which has a high D2 receptor occupancy, also has a high affinity for 5-HT2 receptors (Knable et al, 1997;Schotte et al, 1996;Zhang & Bysmaster, 1999, Beninger, 2006 and it has been suggested that this may act to counterbalance the D2 stimulation, thereby reducing the occurrence of spatial orientation impairments. This provides a distinction in the mechanisms of action of risperidone vs. other antipsychotics agents in developing animals, though the behavioral correlations of such molecular changes are not well difined.…”

Section: Discussionmentioning

confidence: 97%

Clozapine and Olanzapine but not Risperidone Impair the Pre-Frontal Striatal System in relation to Egocentric Spatial Orientation in a Y-Maze

Castro¹,

Reis-Lunardelli²,

Schmidt³

et al. 2007

CNR

View full text Add to dashboard Cite

Many studies indicate a dissociation between two forms of orientation: allocentric orientation, in which an organism orients on the basis of cues external to the organism, and egocentric spatial orientation (ESO) by which an organism orients on the basis of proprioceptive information. While allocentric orientation is mediated primarily by the hippocampus and its afferent and efferent connections, ESO is mediated by the prefronto-striatal system. Striatal lesions as well as classical neuroleptics, which block dopamine receptors, act through the prefronto-striatal system and impair ESO. The purpose of the present study was to determine the effects of the atypical antipsychotics clozapine, olanzapine and risperidone which are believed to exert its antipsychotic effects mainly by dopaminergic, cholinergic and serotonergic mechanisms. A delayed-two-alternative-choice-task, under conditions that required ESO and at the same time excluded allocentric spatial orientation was used. Clozapine and olanzapine treated rats made more errors than risperidone treated rats in the delayed alternation in comparison with the controls. Motor abilities were not impaired by any of the drugs. Thus, with regard to the delayed alternation requiring ESO, clozapine and olanzapine but not risperidone affects the prefronto-striatal system in a similar way as classical neuroleptics does.

show abstract

“…Based on this clinical data and the effects of chronic risperidone administration in rats, we chose a daily estimated drug dose of 3 mg/ kg (31)(32)(33). Total drug load was calculated based on a 400-g animal for a total duration of either 30 (for 50:50 implants) or 150 days (for all other implants), resulting in risperidone doses of 36 or 180 mg, respectively.…”

Section: Drug Dosagementioning

confidence: 99%

In Vitro–In Vivo Correlations of Scalable PLGA-Risperidone Implants for the Treatment of Schizophrenia

et al. 2010

View full text Add to dashboard Cite

show abstract

Dose determination of haloperidol, risperidone and olanzapine using an in vivo dopamine D2-receptor occupancy method in the rat

Cited by 24 publications

References 20 publications

Aripiprazole Increases the PKA Signalling and Expression of the GABAA Receptor and CREB1 in the Nucleus Accumbens of Rats

Aripiprazole Increases the PKA Signalling and Expression of the GABAA Receptor and CREB1 in the Nucleus Accumbens of Rats

Clozapine and Olanzapine but not Risperidone Impair the Pre-Frontal Striatal System in relation to Egocentric Spatial Orientation in a Y-Maze

In Vitro–In Vivo Correlations of Scalable PLGA-Risperidone Implants for the Treatment of Schizophrenia

Contact Info

Product

Resources

About