Antipsychotic drugs may not be triggering apt response in brain cells

January 1st, 2008 - 2:48 pm ICT by admin  

Washington, Jan 1 (ANI): Researchers at the Ohio State University Medical Centre have revealed that some of the antipsychotic drugs that treat depression, schizophrenia and other psychotic conditions by targeting a particular protein on brain cells, might not be prompting appropriate response in the cells.

The study, led by Laura M. Bohn, an associate professor of pharmacology and psychiatry, observed the early chemical events happening inside the neurons when the 2A receptor, a protein on brain cells sensitive to the neurotransmitter serotonin, is stimulated by serotonin and synthetic hallucinogenic agent.

The findings revealed that both the compounds activating the receptor prompted different chemical pathways inside the neuron.

Researchers believe that the findings can harbour the development of drugs that affect serotonin 2A receptor, which is a key target in the treatment of several important mental disorders.

This new insight into how serotonin and a hallucinogenic drug affect this serotonin receptor could lead to changes in how new drugs are screened and developed for depression, schizophrenia and other neuropsychiatric disorders, said Bohn.

Bohn and her colleagues used laboratory-grown cells and a strain of mice that lacked a protein called beta arrestin. They injected normal and experimental mice with a drug hallucinogen DOI. Both groups showed a head-twitch behaviour, a characteristic response in mice to hallucinogens.

Results showed that the receptor responded to serotonin by activating beta-arrestin inside the cell and synthetic hallucinogen caused the receptor to activate only the G proteins.

When the mice were given high doses of serotonin, which typically also causes the head-twitch behaviour, the behaviour occurred in the control animals only, and not in the mice lacking beta-arrestin.

That demonstrates that the signal for serotonin requires beta-arrestin for that biological effect. The synthetic hallucinogen, on the other hand, induces the head-twitch behavior whether beta-arrestin is present or not, Bohn said.

Overall, our findings suggest that the screening of agents intended to be serotonin mimics must also determine if the agent signals through beta-arrestin. That isnt done now, she added.

The findings are published online in the early edition of the Proceedings of the National Academy of Sciences. (ANI)

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