Improving the search for new schizophrenia treatments

Improving the search for new schizophrenia treatments

(Medical Xpress)—Controlling the symptoms of schizophrenia is the job of antipsychotic drugs which block a set of specific neural signals. But the way these drugs work can lead to a host of severe and debilitating long-term motor side-effects.

Current antipsychotic drugs receptors known as Dopamine receptor D2 (D2R). These receptors are responsible for the function of our and affect processes such as reward, motivation and cognition. 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.

Now psychologists at The University of Nottingham have made a discovery which could help in the search for drugs which would work without targeting such critical cellular functions. Their research, funded by the Wellcome Trust, has been published in the academic journal Neuropsychopharmacology.

It is commonly thought that symptoms of schizophrenia arise as a consequence of increased dopamine transmission and that antipsychotic drugs alleviate symptoms by blocking this activity. 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 was surprised to see the same behavioural effect in mice with D2 receptors genetically deleted. Their discovery 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.

The research was led by Dr Paula Moran, an expert in psychopharmacology. She said: "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 . It has always been assumed that DRD2 is necessary for behavioural effects of . These data also suggest the model could be used to identify novel non-D2 that could influence specific psychological processes associated with dysregulation of dopamine without interaction with DRD2."

More information: www.nature.com/npp/journal/vao… full/npp201350a.html

Related Stories

New dopamine brain target discovered

Jan 23, 2007

A team of Canadian researchers, lead by Dr. Susan George and Dr. Brian O'Dowd at the Centre for Addiction and Mental health (CAMH), discovered a distinct dopamine signalling complex in the brain. Composed of two different ...

Receptor limits the rewarding effects of food and cocaine

Jul 12, 2011

(Medical Xpress) -- Researchers have long known that dopamine, a brain chemical that plays important roles in the control of normal movement, and in pleasure, reward and motivation, also plays a central role in substance ...

Researchers identify new drug target for schizophrenia

Aug 13, 2012

(Medical Xpress) -- Researchers at Mount Sinai School of Medicine may have discovered why certain drugs to treat schizophrenia are ineffective in some patients. Published online in Nature Neuroscience, the research will p ...

Recommended for you

Mother-daughter research team studies severe-weather phobia

Sep 19, 2014

No one likes severe weather, but for some just the thought of a thunderstorm, tornado, hurricane or blizzard can severely affect their lives. When blood pressures spike, individuals obsessively monitor weather forecasts and ...

Study: Pupil size shows reliability of decisions

Sep 18, 2014

Te precision with which people make decisions can be predicted by measuring pupil size before they are presented with any information about the decision, according to a new study published in PLOS Computational Bi ...

User comments