Neuropharmacology of Motivation and Reinforcement in Mouse Models of Autistic Spectrum Disorders

Completed

Malanga, C.J.

University of North Carolina

$450,000.00

3 years

Basic & Clinical

Chapel Hill

NC

United States

2008

http://www.unc.edu

City: 
Chapel Hill
State/Province: 
NC
State/Province Full: 
North Carolina
Country: 
United States

Behavioral and drug therapies are commonly used in combination to treat children with autism spectrum disorders. Behavioral therapies involve positive and negative reinforcement of motivated behaviors, the effectiveness of which rely on neural pathways involved in the perception of "reward." However, the degree to which drug therapies can influence behavioral therapies by either enhancing or interfering with “reward” pathways is not well understood. In this study, mouse models of autism spectrum disorders will be used to investigate the effects of drug treatment on motivated behaviors. To model behavioral therapy in mice, intracranial electrical stimulation, or ICSS will be used. ICSS measures motivated behaviors: an electrode implanted in a specific region of a mouse's brain provides a "reward" sensation when a lever is pressed. Animals will self-stimulate by pressing the lever, and the administration of drugs known to affect the reward pathway can modulate this response. In this study, researchers will use ICSS to study motivated behaviors in three commonly used mouse models of autism (Fragile-X syndrome, Rett syndrome, and Angelman syndrome). These mice will be treated with drugs which are known to affect reward pathways, and drugs which are commonly used to treat autism, such as dopamine-blocking neuroleptics. These experiments will determine whether these drugs enhance or impair motivated behaviors in animals with autistic behaviors. Understanding how drug treatment affects behavioral therapy and may allow for the better design of combined therapies in autistic children.