Comparison of risperidone and haloperidol in anxiolytic, antidepressant

and cognitive functions tests in rats.

Nowakowska E., Chodera A., Kus K., Rybakowski J.*, KuŠma A.**

Department of Pharmacology University of Medical Sciences Pozna˝, Poland

* Department of Adult Psychiatry University of Medical Sciences Pozna˝, Poland

** Jannsen Company, Poland.

Introduction

Risperidone is a dopaminergic as well as a 5-HT2 antagonist. The drug was found to exert beneficial effects on both positive and negative symptoms of schizophrenia. Since recently, schizophrenia is regarded as a composite of not only positive and negative but also affective and cognitive symptoms, in this study the effects of risperidone compared with typical neuroleptic haloperidol, on affective and cognitive functions were investigated in rats (locomotor activity, anxiolytic, antidepressive and memory tests).

Materials and methods

The experiments were carried out on male Wistar rats (180-200g). Risperidone (Janssen, Belgium) and Haloperidol (Polfa, Warsaw, Poland) were suspended in 0.5% solution of CMC and administered 0.15 mg/kg p.o. 60 min before the test for anxiolytic, locomotor activity, memory test and Porsolt`s test.

The anxiolytic activity was examined using the "Two compartment exploratory test" by Crawley. The locomotor activity of rats was determined in the "PAN - licensed activity meter". The antidepressive activity was investigated in forced swimming test by Porsolt. The memory assessment was performed by means of the maze test.

Statistic analysis

The statistical significance of the results were evaluated according to the 2-tailed Student "t" test.

Results

Fig.2. The effects of risperidone (0,15 mg/kg p.o.) and haloperidol (0,15 mg/kg p.o.) in the "two compartment exploratory test" for exploring anxiolytic activities.

WSE - white square entrance BSE - black square entrance BWT - black-white transition

 

Table 1. The influence of risperidone and haloperidol on immobility time in Porsolt's test.

 

Immobility time [s]

Drug

Single

administration

Prolonged administration (7 days)

Control group CMC p.o.

247,8 20,0

224,3 18,0

Risperidone 0,15 mg/kg p.o.

220,4 24,0

107,0 12,0*

Haloperidol 0,15 mg/kg p.o.

232,0 19,0

195,4 22,0

 

  • * Statistically significant differences vs. control group and single administration group (p < 0,05)

     

    Table 2. The influence of risperidone and haloperidol after single and prolonged administration on memory processes in the maze test in rats.

  •    

    Food finding time [s]

    Drug

    Doses

    Single administration

    Prolonged administration

       

    7 days

    14 days

    Control group CMC 0,5% p.o.

    21,2 1,3

    19,0 1,4

    17,3 1,5

    Risperidon 0,15 mg/kg p.o.

    15,4 1,4*

    18,4 1,7

    16,9 2,5

    Haloperidol 0,15 mg/kg p.o.

    23,4 2,5

    20,4 2,1

    22,4 2,4

    * Statistically significant differences vs. control group (p < 0,05)

     

    Concluding

    Summarizing we may state, that the antidepressive, anxiolytic and memory improving effects of risperidone found in our animal experiments as well as its LSD-antagonism proved by other authors; may help the understanding of multiple action mechanism of the drug in psychotic patients. It may be then assumed, that thanks to the additional effect of risperidone on 5-HT2 receptors, this drug, in contrast to haloperidol, acts therapeutically on negative symptoms of schizophrenia, but also may exert beneficial effect on mood and cognition in there patients.

    Discussion

    As shown by receptor binding studies, risperidone has not only antidopaminergic but also antiserotonergic properties. This may make it more effective than conventional antipsychotic agents in the treatment of the negative symptoms of schizophrenia.

    Several authors proposed that risperidone reverses the serotonin dysfunction and prefrontal hypoactivity, that are thought to be responsible for the pathogenesis of negative symptoms.

    Drugs which possess the potency to block both serotonergic (5-HT2A) as well as dopaminergic (D2) receptors - like risperidone produce a reliable response rate both to the positive as well as to the negative symptoms of schizophrenia. It deserves noting, that both drugs have a calming effect at doses below the EPS threshold, unlike haloperidol. It is true, that haloperidol is more potent in blocking motility, but at the risk of increased EPS and impaired cognitive function.

    The results of our experiments, my also correspond with favourable effect of risperidone an mood and cognition found in schizophrenic patient.

    Risperidone, in contrast to haloperidol, had a distinct anxiolytic effect and an antidepressive activity, appearing after a 7 days latency time. Our experiments also show, that risperidone unlike haloperidol is effective in improving cognitive functions such as learning and memory what was evidenced by the labyrinth test.