Psychologists at the University of Nottingham (UoN) have made a discovery which could help in the search for drugs to treat the symptoms of schizophrenia without debilitating long-term motor side-effects.
Current antipsychotic drugs target cell receptors known as Dopamine receptor D2 (D2R). These receptors are responsible for the function of our brain cells and affect processes such as reward, motivation and cognition.
Blocking schizophrenia signals
Blocking these signals reduces the symptoms associated with schizophrenia but can cause movement problems similar to Parkinson's disease, weight gain and diabetes, and lower life expectancy.
However, researchers at UoN have developed drug treatments which would work without targeting such critical cellular functions.
Study lead Dr Paula Moran explained: "Our study shows the very surprising finding that antipsychotic drugs haloperidol and clozapine can reduce amphetamine-induced disruption of the ability to ignore irrelevant stimuli in mice that have D2 receptors genetically deleted.
"This suggests that these drugs can have behavioural effects without interacting with D2 receptors. It has always been assumed that DRD2 is necessary for behavioural effects of antipsychotic drugs.
"These data also suggest the model could be used to identify novel non-D2 drug targets that could influence specific psychological processes associated with dysregulation of dopamine without interaction with DRD2."
Same behaviour with D2 deleted
The study team used D-amphetamine (a drug that can induce psychotic symptoms in humans) to model psychotic symptoms seen in schizophrenia in an animal model.
D-amphetamine increases dopamine release disrupting the mouse’s ability to ignore relevant stimuli in the environment. This effect is reversed by administering antipsychotic drugs.
The research team found the same behavioural effect in mice with D2 receptors genetically deleted. A discovery which suggests that this model could be used to identify new non-D2 drug targets that could influence the symptoms of schizophrenia without the side-effects that are seen in current drug treatments.
Read the full paper at: http://www.nature.com/npp/journal/vaop/ncurrent/full/npp201350a.html