Alpha7 nicotinic acetylcholine receptor agonists and PAMs as adjunctive treatment in schizophrenia. An experimental study

Autor: Ninni Påhlsson, Monica M. Marcus, Kent Jardemark, Anna Malmerfelt, Björn Schilström, Annie Möller, Kristin Feltmann, Carl Björkholm, Åsa Konradsson-Geuken, Torgny H. Svensson
Rok vydání: 2016
Předmět:
Male
N-Methylaspartate
alpha7 Nicotinic Acetylcholine Receptor
medicine.drug_class
Dopamine
Prefrontal Cortex
Atypical antipsychotic
Citalopram
Pharmacology
Rats
Sprague-Dawley
Nicotine
Bridged Bicyclo Compounds
03 medical and health sciences
0302 clinical medicine
mental disorders
Excitatory Amino Acid Agonists
medicine
Animals
Pharmacology (medical)
Nicotinic Agonists
Rats
Wistar
Prefrontal cortex
Biological Psychiatry
Risperidone
Depression
Phenylurea Compounds
Pyramidal Cells
medicine.disease
Antidepressive Agents
030227 psychiatry
Disease Models
Animal
Psychiatry and Mental health
Nicotinic agonist
Neurology
Schizophrenia
Benzamides
Adjunctive treatment
Schizophrenic Psychology
Neurology (clinical)
Psychology
Selective Serotonin Reuptake Inhibitors
030217 neurology & neurosurgery
Antipsychotic Agents
medicine.drug
Zdroj: European Neuropsychopharmacology. 26:1401-1411
ISSN: 0924-977X
DOI: 10.1016/j.euroneuro.2016.07.004
Popis: Nicotine has been found to improve cognition and reduce negative symptoms in schizophrenia and a genetic and pathophysiological link between the α7 nicotinic acetylcholine receptors (nAChRs) and schizophrenia has been demonstrated. Therefore, there has been a large interest in developing drugs affecting the α7 nAChRs for schizophrenia. In the present study we investigated, in rats, the effects of a selective α7 agonist (PNU282987) and a α7 positive allosteric modulator (PAM; NS1738) alone and in combination with the atypical antipsychotic drug risperidone for their utility as adjunct treatment in schizophrenia. Moreover we also investigated their utility as adjunct treatment in depression in combination with the SSRI citalopram. We found that NS1738 and to some extent also PNU282987, potentiated a subeffective dose of risperidone in the conditioned avoidance response test. Both drugs also potentiated the effect of a sub-effective concentration of risperidone on NMDA-induced currents in pyramidal cells of the medial prefrontal cortex. Moreover, NS1738 and PNU282987 enhanced recognition memory in the novel object recognition test, when given separately. Both drugs also potentiated accumbal but not prefrontal risperidone-induced dopamine release. Finally, PNU282987 reduced immobility in the forced swim test, indicating an antidepressant-like effect. Taken together, our data support the utility of drugs targeting the α7 nAChRs, perhaps especially α7 PAMs, to potentiate the effect of atypical antipsychotic drugs. Moreover, our data suggest that α7 agonists and PAMs can be used to ameliorate cognitive symptoms in schizophrenia and depression.
Databáze: OpenAIRE
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