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Neurotoxicity of drugs of abuse

 

 

Drugs of abuse are known to increase the levels of neurotransmitters in the brain, primarily via inhibition or reversal of neurotransmitter reuptake transporters. Several antidepressants use a similar mechanism of action, e.g. SSRIs (selective serotonin reuptake inhibitors). In collaboration with the National Poisons Information Center, we will investigate the potential interactions of SSRIs and drugs of abuse on the level of neurotransmitter reuptake transporters using Xenopus oocytes as heterologues expression system.

In addition to inhibition or reversal of neurotransmitter reuptake transporters, we recently demonstrated that drugs of abuse can also interact with GABA receptors, thereby potentially increasing the levels of neurotransmitters and altering neuronal activity. As a secondary aim, we therefore will investigate the effects of several drugs of abuse on neuronal network activity in primary cultures cortical neurons using multi-well multi-electrode arrays.

 

Approach / techniques:

Neurotransmitter transporter expression in Xenopus oocytes; Two-microelectrode voltage clamp technique; Cell culture of primary cultures of cortical neurons; Recordings of electrical activity of cultured cortical neurons using multi-well multi-electrode arrays; Structure-activity relations; Pharmacology & toxicology of inter- and intracellular signaling.