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. 2020 Dec 5;21(23):9281. doi: 10.3390/ijms21239281

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© 2020 by the authors.

Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).

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Effects of A₁R and A_2AR antagonists on anxiolytic-like effect of GUO evaluated by EPM test during a 5 min session. (A–C) Functional competition between GUO and nonselective ARs antagonist caffeine (Caff). Caffeine alone (30 mg/kg) induced anxiolytic effects, as shown by significant increase in time spent in open arms and ratio of time in open arms and total time in arms as compared to control group (Ctrl). Pretreatment with caffeine (30 mg/kg) did not block anxiolytic-like effect of GUO and showed significant increase in time in open arms and ratio of time in open arms and total time in arms as compared to control group. (A–C) Functional competition between caffeine (30 mg/kg) and ADO (30 mg/kg) showed preservation of caffeine anxiolytic effect with significant increase in time spent in open arms and ratio of time in open arms and total time in arms as compared to control group. (D–F) Functional competition between GUO and selective AR antagonists. Selective A₁R antagonist DPCPX (1 mg/kg) was not able to block GUO anxiolytic-like effect, as shown by significant increase in time in open arms and ratio of time in open arms and total time in arms as compared to control group. DPCPX alone did not show significant changes of all EPM parameters as compared to control group. Pretreatment with selective A_2AR antagonist ZM241385 (0.4 mg/kg) was not able to block GUO (30 mg/kg) anxiolytic-like effect, as shown by significant increase in time in open arms and ratio of time in open arms and total time in arms as compared to control group, and ZM241385 alone did not show significant changes of all EPM parameters as compared to control group. Caffeine pretreatment: number of open arm entries [F_(4,61) = 4.021, p < 0.01], time spent in open arms [F_(4,61) = 6.074, p < 0.0005], ratio time in open arms and total time in arms [F_(4,61) = 6.267, p < 0.0005]. DPCPX and ZM241385 pretreatment: number of open arm entries [F_(5,76) = 2.558, p < 0.05], time spent in open arms [F_(5,76) = 4.637, p = 0.001], ratio time in open arms and total time in arms [F_(5,76) = 4.303, p < 0.002]. Each bar represents the mean value ± SD. Tukey test: * p < 0.05, ** p < 0.01, *** p < 0.001. Ctrl raw mean values: (A) 6.07; (B) 55.35 s; (C) 0.31; (D) 8.44; (E) 75.79 s; (F) 0.33.