A new study on rats has found that a new group of painkillers that block a receptor called TRPV1 may interfere with brain functions such as learning and memory.
The team of researchers led by Julie Kauer, has found that the TRPV1 receptor regulates a neural mechanism called long-term depression (LTD), believed to be essential for establishing memory pathways in the brain.
TRPV1, or "transient receptor potential vanilloid 1," is a pain receptor whose activation causes the pain in inflammation. It is also triggered by harmful chemicals such as the chili pepper compound capsaicin.
According to the researchers, their findings also suggest that the function of TRPV1 in neural tissue may explain reported side effects of the anti-obesity drug Acomplia, widely used outside the U.S and it was banned in U.S. because of concerns that the drug increases risk of depression and suicide.
Since long, drug companies have been testing TRPV1 receptor blockers to treat the pain of inflammation and nerve damage in the peripheral nervous system (PNS). But, in addition to being expressed in the PNS, TRPV1 is also expressed in areas of the central nervous system (CNS), including the hippocampus, the brain's learning center. However, its function in the brain was not well established.
The researchers conducted experiments with rat brain slices to explore if TRPV1 plays a role in LTD, which is a weakening of the signaling between neurons that takes place at the connections called synapses. LTD, and the counterpart strengthening of connections, called long-term potentiation, are important to a process called plasticity - the formation of neural pathways in learning.
It was found that researchers could block LTD in the brain slices using drugs that block TRPV1. Also, they could induce LTD using the TRPV1-activating compound capsaicin. They also found that genetically knocking out the TRPV1 receptor in mice drastically reduced LTD in the animals.
"In this study, we show for the first time that TRPV1 receptors are necessary and sufficient for a novel form of long-term depression at excitatory synapses. The broad distribution of TRPV1 receptors in the brain suggests that these receptors could play a similar role in synaptic plasticity throughout the CNS," concluded the researchers.
They said that their findings indicate that drugs targeting TRPV1 could act on pain receptors in the PNS, as well as in the brain. They also wrote that their findings and those of other researchers "indicate that drugs that bind to CNS TRPV1 receptors are likely to influence more than just pain-related functions. Further work will help to ascertain whether hippocampal TRPV1 receptors could provide novel drug targets for neurological disorders," they wrote.
They concluded that their findings suggest a mechanism for the reported side effects of the anti-obesity drug Acomplia.
"A large percentage of patients stop taking this drug as a result of psychiatric side effects, and our findings suggest the possibility that some of the central effects of [Acomplia] result from the antagonism of TRPV1 receptors ...," they wrote.
The findings of this study are published in the latest issue of the journal Neuron, published by Cell Press.