Angel's Dust/Uppers and Schizophrenia
The answer turns out to be, surprisingly, a lot. The two most popular hypotheses about the neurology about schizophrenia are the dopamine and glutamine hypotheses, which both state that an imbalance of neurotransmitters in the brain causes clinical symptoms of psychosis including delusions, halllucinations, disorganized speech, catatonic behavior, poor memory/concentration, and other cognitive deficiencies. The dopamine hypothesis' stance that psychotic behavior is caused by an imbalance of dopamine is supported by the fact that when normal people are given amphetamine, a D_2 receptor agonist (stimulator of a dopamine receptor), they exhibit symptoms indistinguishable from the symptoms that true schizophrenics exhibit. The glutamergic hypothesis basically states that a lack of the neurotransmitter glutamate in the brain; the hypothesis is supported by the state of psychosis that PCP (phenocyclidine/angel's dust), an antagonist (agent that binds to a particular receptor but doesn't stimulate it) of a major set of receptors in the glutamatergic system. So the lab is studying not just one of these neurotransmitters but the neuropathways that these transmitters affect through the testing of pharmaceuticals. Of course, it's a lot more complicated than that, but I don't think the grant will fit on the post.
What I've been doing/will be doing is just a miniscule, miniscule, miniscule part of the entire five year project. I'm studying sensorimotor gating through examining prepulse inhibition (PPI). Sensorimotor gating is the ability of an organism to filter out overwhelmingly large amount of information it receives, and schizophrenics are less capable of filtering out the information than controls. "Prepulse inhibition is the process whereby a relatively mild stimulus – the prepulse – acts through CNS synapses to suppress the response to a strong, startle-eliciting stimulus when the prepulse precedes the startle stimulus by a brief duration (in mammals, about 10–500milliseconds)" (Sensorimotor Gating: Startle Submits to Presynaptic Inhibition Current Biology, Volume 14, Issue 6, Pages R247-R249 M. Nusbaum, D. Contreras).
Schizophrenics exhibit a reduction in PPI, but the reduction can be corrected using neuroleptics (antipsychotics that help the patients ameliorate their symptoms). The trials that I've been helping doing test the PPI responses of mice after they've been given a stimulant that causes psychosis and then either a neuroleptic or a vehicle, which is saline that acts as a control that shows how effective the neuroleptic really is.
