Anxiolytic and antidepressant-like activities of the novel and potent non-imidazole histamine H₃ receptor antagonist ST-1283

Figures & data

Figure 1 Effects of acute ST-1283 pretreatment on exploratory behavior on the ele vated plus maze test. ST-1283 dose-dependently increased the percentage of time spent on the open arms of the elevated plus maze (A), increased the number of entries into the open arms (B) and the percentage of entries into the open arms (C). Pretreatment with the H₃R antagonist did not affect the number of closed arm entries (D).

Notes: *Denotes significant differences between drug doses and saline controls (P<0.05); ^#denotes significant differences between diazepam and saline controls (P<0.001). Vehicle n=9; ST-1283 5 mg/kg n=10; ST-1283 7.5 mg/kg n=7, diazepam n=8. Data are shown as the mean ± standard error of the mean.
Abbreviations: DZP, diazepam; OA, open arms.

Figure 2 Effects of acute ST-1283 pretreatment on anxiety-like behavior in the open field test and marbles burying test. In the open field test, ST-1283 had no effect on total line crossing (A) but dose-dependently increased the time spent in the center of the arena (B). In the marbles burying test, acute ST-1283 decreased the number of buried marbles (C) and the time spent digging (D).

Notes: *Denotes significant differences between drug doses and saline controls (P<0.05); ^#denotes significant differences between diazepam and saline controls (P<0.001). Vehicle n=9; ST-1283 5 mg/kg n=10; ST-1283 7.5 mg/kg n=7, DZP n=8. Data are shown as the mean ± standard error of the mean.
Abbreviation: DZP, diazepam.

Figure 3 Effects of acute ST-1283 pretreatment on depression-like behavior in the TST, the novelty suppressed feeding test, and the forced swim test. Acute ST-1283 decreased immobility time in the TST (A) and decreased the feeding latency in the novelty suppressed feeding test (B). However, ST-1283 did not affect eating in the home cage (C). Similarly, ST-1283 dose-dependently decreased the immobility time in the forced swim test (D).

Notes: *Denotes significant differences between drug doses and saline controls (P<0.05); ^#denotes significant differences between fluoxetine and saline controls (P<0.001). Vehicle n=9; ST-1283 5 mg/kg n=10; ST-1283 7.5 mg/kg n=7, fluoxetine n=8. Data are shown as the mean ± standard error of the mean.
Abbreviations: TST, tail suspension test; FXT, fluoxetine; FST, forced swim test.

Figure 4 Effects of acute RAMH pretreatment on ST-1283-induced anxiolytic effects in the elevated plus maze test. RAMH pretreatment abrogated the effects of ST-1283 on the percentage of time spent in the open arms (A), the number of entries into the open arms (B), and the percentage of entries into the open arms (C). Pretreatment with the H₃R agonist RAMH did not affect the number of closed arm entries (D).

Notes: *Denotes significant differences between ST-1283 and saline controls (P<0.05); ^#denotes significant differences between RAMH and ST-1283 (P<0.05). Vehicle n=7; ST-1283 7.5 mg/kg n=6, RAMH n=8. Data are shown as the mean ± standard error of the mean.
Abbreviations: CA, closed arm; OA, open arm; RAMH, R-α-methylhistamine.

Figure 5 Effects of acute RAMH pretreatment on ST-1283-induced anxiolytic effects in the open field test and marbles burying test. In the open field test, RAMH pretreatment had no effect on total line crossing (A) but abrogated the effects of ST-1283 on the time spent in the center of the arena (B). In the marbles burying test, acute RAMH pretreatment blocked the effects of ST-1283 on the number of buried marbles (C) and time spent digging (D).

Notes: *Denotes significant differences between ST-1283 and saline controls (P<0.05); ^#denotes significant differences between RAMH and ST-1283 (P<0.05). Vehicle n=7; ST-1283 7.5 mg/kg n=6, RAMH n=8. Data are shown as the mean ± standard error of the mean.
Abbreviation: RAMH, R-α-methylhistamine.

Figure 6 Effects of acute RAMH pretreatment on ST-1283-induced antidepressant effects in the TST, feeding latency and food intake in the NSF, and FST.

Notes: *Denotes significant differences between ST-1283 and saline controls (P<0.05); ^#denotes significant differences between RAMH and ST-1283 (P<0.05). Vehicle n=7; ST-1283 7.5 mg/kg n=6, RAMH n=8. Data are shown as the mean ± standard error of the mean.
Abbreviations: RAMH, R-α-methylhistamine; FST, forced swim test; NSF, novelty suppressed feeding; TST, tail suspension test.