Fluoxetine and hyperforin appear to act like a known glutamate reuptake inhibitor by increasing EPSP duration in the crayfish neuromuscular junction

Abstract

Commonly used antidepressants, fluoxetine and hyperforin inhibit serotonin reuptake to treat patients. There is evidence that one of these selective serotonin reuptake inhibitors (SSRIs), hyperforin, also affects glutamate, another neurotransmitter (Di Carlo, 2001). Our study was to determine if another SSRI, fluoxetine, had similar effects on glutamate reuptake inhibition as hyperforin. We first examined the effects of the known glutamate reuptake inhibitor, aminocaproic acid, in order to establish a framework through which to compare the effects of SSRIs on glutamate reuptake inhibition. In addition we examined the effects of the SSRIs when they were used in conjunction. The study was conducted in the crayfish neuromuscular junction due to its simplicity. We compared the duration of EPSPs under normal and experimental conditions, in order to determine the similarities of the effects on glutamate reuptake inhibition between the chemicals. It was shown that fluoxetine exhibited the largest increase in duration, hyperforin showed the smallest increase, and the combination of fluoxetine and hyperforin exhibited an increase in EPSP duration that was between that of the two SSRIs alone. We contend that fluoxetine had a greater effect on the reuptake inhibition of glutamate than hyperforin. This questions the safety of using fluoxetine, the main active ingredient in Prozac due to unsuspected side effects. An unexpected result came when fluoxetine and hyperforin were used together in that the averaging affect of the two chemicals presents that possibility that combining these two drugs is safer than using fluoxetine alone, in regards to glutamate reuptake inhibition.