Oral fluoxetine treatment changes serotonergic sympatho-regulation in experimental type 1 diabetes

Fluoxetine Treatment Decreases Cardiac Vagal Input and Alters the Serotonergic Modulation of the Parasympathetic Outflow in Diabetic Rats

“…In the diabetic control group ( n = 5), this hyperglycaemia remained stable until day 28 (488 ± 12 mg/dL; p < 0.05 versus day 0). The chronic administration of fluoxetine ( n = 115) significantly diminished glucose levels in diabetic animals (270 ± 7 mg/dL; p < 0.05 versus day 0, day 14 and diabetic control group at day 28), even though glycaemia did not return to basal values, as already described [ 27 ]. In relation to body weight gain, as previously shown by our group [ 27 ], the chronic administration of fluoxetine restricted body weight increase (281 ± 10 g at day 0; 339 ± 5 g at day 28 in diabetic control group— p < 0.05 versus day 0; and, 287 ± 4 g at day 28 in FT diabetic group— p < 0.05 versus day 28 of diabetic control group).…”

“…After anaesthesia and pithing, fluoxetine treatment did not modify basal MBP and HR compared to FT normoglycaemic [ 25 , 30 ] and non-treated diabetic rats (current data, [ 19 , 20 , 27 ]). While most of the agonists and antagonists used in this work did not modify either MBP or HR, it is remarkable that all doses of 5-HT and α-methyl-5-HT induced increases in MBP that immediately restored to basal values as occurred in FT normoglycaemic animals [ 25 ].…”

“…In our experiments, alloxan administration induced, from day 2 after injection, a syndrome resembling human T1DM [ 19 , 20 , 28 ] that was confirmed by measurement of blood glucose levels. Our animals were chronically treated with the antidepressant fluoxetine, which increases extracellular serotonin levels [ 29 ] at a dose and period (10 mg/kg/day; 14 days) that originate levels in plasma similar to patients treated with therapeutic doses [ 25 , 27 , 30 , 31 , 32 ]. Our results reveal that chronic fluoxetine treatment significantly reduces blood glucose levels compared to diseased (alloxan) animals without treatment, even though glycaemia does not return to normal levels, as we have previously described [ 27 ].…”

“…Our animals were chronically treated with the antidepressant fluoxetine, which increases extracellular serotonin levels [ 29 ] at a dose and period (10 mg/kg/day; 14 days) that originate levels in plasma similar to patients treated with therapeutic doses [ 25 , 27 , 30 , 31 , 32 ]. Our results reveal that chronic fluoxetine treatment significantly reduces blood glucose levels compared to diseased (alloxan) animals without treatment, even though glycaemia does not return to normal levels, as we have previously described [ 27 ]. Similarly, body weight increase was significantly lower in FT compared to control diabetic rats [current results,27].…”

“…To further test the receptors involved in the 5-CT effect, selective receptor agonists and antagonists were tested. As 5-CT has affinity not only for 5-HT 1 receptor type, but also for 5-HT 7 receptor type [ 21 ], the possible implication of 5-HT 7 receptors was achieved by administering 5-CT at low and high doses in the presence of the selective 5-HT 7 receptor antagonist, SB269970 [ 27 , 37 ]. SB269970 did not modify the inhibitory effect of low doses of 5-CT, but confirmed the involvement of 5-HT 7 receptors in the high doses of 5-CT-mediated vagopotentiation, since in the presence of this antagonist, 5-CT manifested an inhibitory action.…”