Effect of repeated co-treatment with antidepressant drugs and a low dose of risperidone on the behavioral reactivity of central serotonin and dopamine systems in mice
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1
Institute of Pharmacology PAS, Poland
Major depression occurs in up to 10% of the human population, and all the currently used antidepressant drugs (ADs) are effective as a monotherapy in ca. 60-70% of patients. Among agents that are expected to potentiate the efficacy of ADs there are atypical antypsychotics (e.g., olanzapine, risperidone). Several clinical reports have postulated a beneficial effect of an additional low dose of risperidone in the ongoing treatment with ADs. The latter drug is ca. 10-20 times more potent in its binding to serotonin 5-HT2A receptors than to dopamine D2 ones; moreover, it produces minimal extrapyramidal side-effects compared to classical antipsychotics. To understand the mechanism of the clinical efficacy of an AD and an atypical antipsychotic (a combination therapy) in treatment-resistant depression, in the present study we examined the effect of co-treatment with ADs belonging to different pharmacological groups and a low dose of risperidone, given separately or jointly, on the behavioral reactivity of the central 5-HT1A and 5-HT2A or dopamine systems in male C57BL/6J mice. The obtained results showed that repeated citalopram, fluoxetine or mirtazapine (but not desipramine), co-administered with risperidone (0.1 mg/kg), induced a more potent inhibition of the behavioral syndrome evoked by 5-HT1A and 5-HT2A receptor agonists (8-OH-DPAT and DOI, respectively), but did not change the action of amphetamine (a dopamine agent) compared to the treatment with either drug alone. The presented results indicate that a low dose of risperidone enhances the action of citalopram, fluoxetine or mirtazapine, and that central 5-HT1A and 5-HT2A receptors may play some role in these effects. Furthermore, they may be of importance to the pharmacotherapy of drug-resistant depression. Funding: Supported by grant POIG. 01.01.02-12-004/09-00 from the European Regional Development Fund.
Keywords:
Depression,
Neuropsychiatry
Conference:
XI International Conference on Cognitive Neuroscience (ICON XI), Palma, Mallorca, Spain, 25 Sep - 29 Sep, 2011.
Presentation Type:
Poster Presentation
Topic:
Poster Sessions: Neuropsychiatric Applications
Citation:
Rogoz
Z,
Kabzinski
M and
Sadaj
W
(2011). Effect of repeated co-treatment with antidepressant drugs and a low dose of risperidone on the behavioral reactivity of central serotonin and dopamine systems in mice.
Conference Abstract:
XI International Conference on Cognitive Neuroscience (ICON XI).
doi: 10.3389/conf.fnhum.2011.207.00231
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Received:
21 Nov 2011;
Published Online:
28 Nov 2011.
*
Correspondence:
Dr. Zofia Rogoz, Institute of Pharmacology PAS, Krakow, Poland, rogoz@if-pan.krakow.pl