Treatment with the selective serotonin reuptake inhibitor, fluoxetine, attenuates the fish hypoxia response

Abstract

The selective serotonin reuptake inhibitor (SSRI) fluoxetine (FLX), the active ingredient of the antidepressant drug Prozac, inhibits reuptake of the neurotransmitter, serotonin (5-HT; 5-hydroxytryptamine), into cells by the 5-HT transporter (SERT). Given the role of 5-HT in oxygen detection and the cardiovascular and ventilatory responses of fish to hypoxia, we hypothesized that treatment of the Gulf toadfish, Opsanus beta, with FLX would interfere with their response to hypoxia. Toadfish treated intra-arterially with 3.4 μg.g(-1) FLX under normoxic conditions displayed a transient tachycardia and a biphasic caudal arterial blood pressure (PCA) response that are in direct conflict with the typical hypoxia response. Fish injected intraperitoneally with FLX under normoxia had resting cardiovascular and ventilatory parameters similar to controls. Upon exposure to hypoxia, control toadfish exhibit a significant bradycardia, reduction in PCA and an increase in ventilatory amplitude (VAMP) without any changes in ventilatory frequency (fV). Fish treated IP with 10 μg.g(-1) FLX showed an interference in the cardiovascular and ventilatory response to hypoxia. Interestingly, when treated with 25 μg.g(-1) FLX, the bradycardia and VAMP response to hypoxia were similar to control fish while the PCA response to hypoxia was further inhibited. These results suggest that SERT inhibition by FLX may hinder survival in hypoxia.

Figure 1

The effect of IA saline (1 μl saline⁻¹.g fish⁻¹; N = 7) or FLX (3.4 μg. μl saline⁻¹.g fish⁻¹; N = 9) injection on (A) fH, (B) P_P or (C) P_CA. Injections occur at t = 0. Δ values are means ± S.E.M; *P < 0.05 indicates a significant change across the time points specified by the line as measured by one-way RM ANOVA; ^†P < 0.05 indicates a significant difference from the value at t = 0; ^‡P < 0.05 indicates a significant difference from the value at t = 1.

Figure 2

The effect of IA saline (1 μl saline⁻¹.g fish⁻¹; N = 7) or FLX (3.4 μg. μl saline⁻¹.g fish⁻¹; N = 9) injection on (A) V_AMP or (B) fV. Injections occur at t = 0. *P < 0.05 indicates a significant change across the time points specified by the line as measured by one-way RM ANOVA.

Figure 3

Heart rate (fH) in (A) fish treated with 0 μg FLX·g fish⁻¹ (control; N = 11) (B) 10 μg FLX·g fish⁻¹ (N = 9) or (C) 25 μg FLX·g fish⁻¹(N = 6) during normoxia and in response to hypoxia exposure over time. Gray boxes indicate hypoxia exposure. Δ values are means ± S.E.M; *P < 0.05 indicates a significant change across the time points specified by the line as measured by one-way RM ANOVA; ^†P < 0.05 indicates a significant difference from the value at t = 0.

Figure 4

Pulse pressure (P_P) in (A) fish treated with 0 μg FLX·g fish⁻¹ (control; N = 8) (B) 10 μg FLX·g fish⁻¹ (N = 4) or (C) 25 μg FLX·g fish⁻¹ (N = 6) during normoxia and in response to hypoxia exposure over time. Δ values are means ± S.E.M; *P < 0.05 indicates a significant change across the time points specified by the line as measured by one-way RM ANOVA; ^†P < 0.05 indicates a significant difference from the value at t = 0.

Figure 5

Caudal arterial blood pressure (P_CA) in (A) fish treated with 0 μg FLX·g fish⁻¹ (control; N = 8) (B) 10 μg FLX·g fish⁻¹ (N = 4) or (C) 25 μg FLX·g fish⁻¹ (N = 6) during normoxia and in response to hypoxia exposure over time. Δ values are means ± S.E.M; *P < 0.05 indicates a significant change across the time points specified by the line as measured by one-way RM ANOVA.

Figure 6

Ventilatory amplitude (V_AMP) in (A) fish treated with 0 μg FLX·g fish⁻¹ (control; N = 12) (B) 10 μg FLX·g fish⁻¹ (N = 5) or (C) 25 μg FLX·g fish⁻¹ (N = 5) during normoxia and in response to hypoxia exposure over time. Δ values are means ± S.E.M; *P < 0.05 indicates a significant change across the time points specified by the line as measured by one-way RM ANOVA.