Project 11

Pharmacogenetics of potentiated apomorphine effects: an animal genetic model of neuroleptic malignant syndrome in schizophrenia?

We have bred lines of mice that inherit a potentiated hypothermic response to the dopamine agonist, apomorphine. This is of interest, because the psychotic symptoms of schizophrenia appear to depend on an enhanced sensitivity of the dopamine system, and because treatment of patients with dopaminergic drugs sometimes leads to a fatal fever, called “neuroleptic malignant syndrome”. This project will be directed towards assessing whether an abnormal hyperthermic response occurs in this mouse model, also investigating neural substrates for the mechanism of the inherited phenotype.

References

Lagerspetz KYH, Koprowski H, Darnell M, Tarkkonen H (1973) Thermoregulation in group B arbovirus-resistant and group B arbovirus-susceptible mice. Am J Physiol 225, 532-537.

Brown JS Jr (1994) Geographic correlation of schizophrenia to ticks and tick-borne encephalitis. Schizophr Bull 20, 755-775.

Stoddart CW, Martin-Iverson MT, Jablensky A, Urosevic N (2004) A novel mouse Chr5 locus Diht controls dopamine-induced hypothermia. Mammalian Genome 15: 901-913

Silvia OJ, Shellam GR, Urosevic N (2001) Innate resistance to Flavivirus infection in mice controlled by Flv is nitric oxide-independent. J Gen Virol 82, 603-607.