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The GABA B receptor agonist CGP44532 and the positive modulator GS39783 reverse some behavioural changes related to positive syndromes of psychosis in mice
Author(s) -
Wierońska JM,
Kusek M,
Tokarski K,
Wabno J,
Froestl W,
Pilc A
Publication year - 2011
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.2011.01301.x
Subject(s) - allosteric modulator , amphetamine , catalepsy , pharmacology , haloperidol , agonist , excitatory postsynaptic potential , chemistry , neurotransmission , psychosis , gabaa receptor , neuroscience , receptor , biology , medicine , biochemistry , dopamine , psychiatry
BACKGROUND AND PURPOSE An important role of GABAergic neurotransmission in schizophrenia was proposed a long time ago, but there is limited data to support this hypothesis. In the present study we decided to investigate GABA B receptor ligands in animal models predictive for the antipsychotic activity of drugs. The GABA B receptor antagonists CGP51176 and CGP36742, agonist CGP44532 and positive allosteric modulator GS39783 were studied. EXPERIMENTAL APPROACH The effects of all ligands were investigated in MK‐801‐ and amphetamine‐induced hyperactivity tests. The anti‐hallucinogenic‐like effect of the compounds was screened in the model of head twitches induced by (±)1‐(2.5‐dimethoxy‐4‐iodophenyl)‐2‐aminopropane (DOI). Furthermore, the effect of GS39783 and CGP44532 on DOI‐induced frequency of spontaneous excitatory postsynaptic currents (EPSCs) in slices from mouse brain frontal cortices was investigated. The anti‐cataleptic properties of the compounds were also assessed. KEY RESULTS The GABA B receptor activators CGP44532 and GS39783 exhibited antipsychotic‐like effects both in the MK‐801‐ and amphetamine‐induced hyperactivity tests, as well as in the head‐twitch model in mice. Such effects were not observed for the GABA B receptor antagonists. DOI‐induced increased frequency of spontaneous EPSCs was also decreased by the compounds. Moreover, CGP44532 and GS39783 inhibited haloperidol‐induced catalepsy and EPSCs. CONCLUSION AND IMPLICATIONS These data suggest that selective GABA B receptor activators may be useful in the treatment of psychosis.