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Selective adrenergic alpha2C receptor antagonist ameliorates acute phencyclidine-induced schizophrenia-like social interaction deficits in rats

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Date
2018
Author
Savolainen, Katja
Ihalainen, Jouni
Jalkanen, Aaaro J
Forsberg, Markus M
Unique identifier
10.1007/s00213-018-5130-2
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Citation
Savolainen, Katja. Ihalainen, Jouni. Jalkanen, Aaaro J. Forsberg, Markus M. (2018). Selective adrenergic alpha2C receptor antagonist ameliorates acute phencyclidine-induced schizophrenia-like social interaction deficits in rats.  PSYCHOPHARMACOLOGY, [Epub ahead of print 10 Dec 2018], 10.1007/s00213-018-5130-2.
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CC BY http://creativecommons.org/licenses/by/4.0/
Abstract

Rationale
Social withdrawal is a core feature of the negative symptoms of schizophrenia. Currently available pharmacotherapies have only limited efficacy towards the negative symptoms, i.e., there is a significant unmet medical need in the treatment of these symptoms.

Objective
We wanted to confirm whether selective adrenergic α2C receptor (AR) antagonist therapy could ameliorate acute phencyclidine (PCP)-induced schizophrenia-like social interaction deficits in rats, and to compare the effects of an α2C AR antagonist to another putative therapeutic alternative, an α7 nicotinic acetylcholine receptor (nAChR) partial agonist, as well against three commonly used atypical antipsychotics.

Methods
Here, we used acute PCP administration and modified a protocol for testing social interaction deficits in male Wistar rats and then used this model to compare the effects of an α2C AR antagonist (ORM-13070 0.3 and 1.0 mg/kg s.c.) with an α7 nAChR partial agonist (EVP-6124 0.3 mg/kg s.c.) and three atypical antipsychotics (clozapine 2.5 mg/kg i.p., risperidone 0.04 and 0.08 mg/kg s.c., olanzapine 0.125 and 0.5 mg/kg s.c.) on social interaction behavior.

Results
Acute PCP (1.5 mg/kg s.c.) produced robust and reproducible deficits in social interaction behavior without affecting locomotor activity. The selective α2C AR antagonist significantly ameliorated PCP-induced social interaction deficits. In contrast, neither the partial α7 nAChR agonist nor any of the three atypical antipsychotics were able to reverse the behavioral deficits at the selected doses.

Conclusion
Our findings confirm that α2C AR antagonism is a potential mechanism for the treatment of the negative symptoms of schizophrenia.

Subjects
α2C adrenergic receptor antagonist   α7 nicotinic acetylcholine receptor partial agonist   atypical antipsychotics   rat   schizophrenia   social interaction deficit   
URI
https://erepo.uef.fi/handle/123456789/7197
Link to the original item
http://dx.doi.org/10.1007/s00213-018-5130-2
Publisher
Springer Nature
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  • Terveystieteiden tiedekunta
University of Eastern Finland
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