Fig 1.
Antagonistic effects of histone deacetylase (HDAC) inhibitors or cannabinoid type 1 (CB1) agonist against anxiety-like behaviors.
The parameter values of the elevated plus-maze test at the 2 h time point after the last nicotine (NC) (0.8 mg/kg, s.c.) or immobilization stress (IM) (10 min) treatment are shown as means ± S.D. (n = 10) for each HDAC inhibitor or CB1 ligand co-treatment group (with each i.p. dose (mg/kg)). (A) Sodium butyrate (SB) co-treatment groups (SB groups); (B) Valproic acid (VA) co-treatment groups (VA groups); (C) ACPA (arachidonylcyclopropylamide; AC) co-treatment groups (AC groups); (D) SR 141716A (N-(Piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide hydrochloride; SR) co-treatment groups (SR groups). The data for the control, NC, IM, and NC plus IM (NC-IM) groups without any HDAC inhibitor or CB1 ligand co-treatments, as well as the HDAC inhibitor- and CB1 ligand-only groups, are also shown. * (p<0.05), ** (p<0.01): significant attenuation as compared to the control group; ++ (p<0.01): significant increase as compared to the NC, IM, or NC-IM group without any co-treatments; ## (p<0.01): significant attenuation as compared to the IM group without any co-treatments.
Fig 2.
Antagonistic effects of histone deacetylase (HDAC) inhibitors or cannabinoid type 1 (CB1) agonist against depression-like behaviors.
The parameter values of the forced swimming test at the 2 h time point after the last nicotine (NC) (0.8 mg/kg, s.c.) or immobilization stress (IM) (10 min) treatment are shown as means ± S.D. (n = 10) for each HDAC inhibitor or CB1 ligand co-treatment group (with each i.p. dose (mg/kg)). (A) Sodium butyrate (SB) co-treatment groups (SB groups); (B) Valproic acid (VA) co-treatment groups (VA groups); (C) ACPA (arachidonylcyclopropylamide; AC) co-treatment groups (AC groups); (D) SR 141716A (N-(Piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide hydrochloride; SR) co-treatment groups (SR groups). The data for the control, NC, IM, and NC plus IM (NC-IM) groups without any HDAC inhibitor or CB1 ligand co-treatments, as well as the HDAC inhibitor- and CB1 ligand-only groups, are also shown. * (p<0.05), ** (p<0.01): significant attenuation as compared to the control group; + (p<0.05), ++ (p<0.01): significant increase as compared to the NC, IM, or NC-IM group without any co-treatments.
Fig 3.
Interacting effects between cannabinoid type 1 (CB1) antagonist (SR 141716A) and efficacious (anxiolytic-like) histone deacetylase (HDAC) inhibitors or CB1 agonist against anxiety-like behavioral alterations caused by nicotine (NC) and/or immobilization stress (IM).
The parameter values of the elevated plus-maze test at the 2 h time point after the last NC (0.8 mg/kg, s.c.) or IM (10 min) treatment are shown as means ± S.D. (n = 10) for each HDAC inhibitor or CB1 ligand “plus” SR 141716A (N-(Piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide hydrochloride; SR) co-treatment group (with each i.p. dose (mg/kg)). (A) Sodium butyrate (SB) plus SR co-treatment groups (SB+SR groups); (B) Valproic acid (VA) plus SR co-treatment groups (VA+SR groups); (C) ACPA (arachidonylcyclopropylamide; AC) plus SR co-treatment groups (AC+SR groups). The data for the control, NC, IM, and NC plus IM (NC-IM) groups without any HDAC inhibitor or CB1 ligand co-treatments, as well as the HDAC inhibitor-, CB1 agonist-, HDAC inhibitor plus SR-, and CB1 agonist plus SR-only groups, are also shown. * (p<0.05), ** (p<0.01): significant attenuation as compared to the control group; + (p<0.05), ++ (p<0.01): significant increase as compared to the NC, IM, or NC-IM group without any co-treatments; $ (p < 0.05), $ $ (p < 0.01): significant attenuation as compared to the NC, IM, or NC-IM group co-treated with the efficacious HDAC inhibitor or CB1 agonist.
Fig 4.
Interacting effects between cannabinoid type 1 (CB1) antagonist (SR 141716A) and efficacious (antidepressant-like) histone deacetylase (HDAC) inhibitors or CB1 agonist against depression-like behavioral alterations caused by nicotine (NC) and/or immobilization stress (IM).
The parameter values of the forced swimming test at the 2 h time point after the last NC (0.8 mg/kg, s.c.) or IM (10 min) treatment are shown as means ± S.D. (n = 10) for each HDAC inhibitor or CB1 ligand “plus” SR 141716A (N-(Piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide hydrochloride; SR) co-treatment group (with each i.p. dose (mg/kg)). (A) Sodium butyrate (SB) plus SR co-treatment groups (SB+SR groups); (B) Valproic acid (VA) plus SR co-treatment groups (VA+SR groups); (C) ACPA (arachidonylcyclopropylamide; AC) plus SR co-treatment groups (AC+SR groups). The data for the control, NC, IM, and NC plus IM (NC-IM) groups without any HDAC inhibitor or CB1 ligand co-treatments, as well as the HDAC inhibitor-, CB1 agonist-, HDAC inhibitor plus SR-, and CB1 agonist plus SR-only groups, are also shown. * (p<0.05), ** (p<0.01): significant attenuation as compared to the control group; + (p<0.05), ++ (p<0.01): significant increase as compared to the NC, IM, or NC-IM group without any co-treatments; $ (p < 0.05), $ $ (p < 0.01): significant attenuation as compared to the NC, IM, or NC-IM group co-treated with the efficacious HDAC inhibitor or CB1 agonist.