THE ROLE OF THE D3 DOPAMINE RECEPTOR IN RODENT BEHAVIORAL RESPONSES TO NOVELTY AND PSYCHOSTIMULANTS

 
 
 
 

THE ROLE OF THE D3 DOPAMINE RECEPTOR IN RODENT BEHAVIORAL RESPONSES TO NOVELTY AND PSYCHOSTIMULANTS

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Title: THE ROLE OF THE D3 DOPAMINE RECEPTOR IN RODENT BEHAVIORAL RESPONSES TO NOVELTY AND PSYCHOSTIMULANTS
Author: PRITCHARD, LAUREL M.
Description: Brain dopamine signaling is important for regulation of a variety of complex functions, including locomotor activity, cognition, motivation, and emotion. In particular, abnormalities in dopamine signaling have been implicated in psychiatric disorders, including psychotic disorders, such as schizophrenia, and substance abuse and addiction. The D3 dopamine receptor is of particular interest due to its restricted localization in limbic brain regions, which are associated with motivation and emotion, and to its apparently inhibitory role in regulating cellular and behavioral responses to dopamine. However, a clear understanding of the functional role of the D3 receptor has been hampered by a lack of sufficiently selective pharmacological tools. The aims of these studies were to clarify the role of the D3 receptor in rodent behaviors by establishing appropriate conditions for the use of currently available agonists, assessing the behavioral effects of new, highly selective antagonists, and examining relationships between D3 receptor expression and individual differences in behavior. In the first set of studies, the effects of preferential D3 receptor agonists on mouse locomotor behavior were assessed. When administered prior to placement in a novel environment, these agonists inhibited locomotor activity in wild-type mice, but not those lacking functional D3 receptors, suggesting that the behavioral effects were mediated by D3 receptors. Additionally, these compounds were without effect in mice that had been acclimated to the testing chamber prior to drug administration. These results suggest that D3 receptor stimulation is inhibitory to novelty-stimulated locomotion and establish appropriate conditions for selective D3 receptor activation in vivo. In the second set of studies, the behavioral effects of a highly-selective D3 receptor antagonist were assessed. This antagonist stimulated basal locomotor activity and enhanced amphetamine-stimulated locomotion in wild-type, but not D3 receptor mutant mice, in support of an inhibitory role for the D3 receptor in rodent locomotor behavior. In the third set of studies the role of the D3 receptor in regulation of behavioral responses to novelty was examined in a rat model of individual differences in response to novelty. Reduced D3 receptor mRNA expression in medial prefrontal cortex was associated with increased locomotor response to a novel environment. These results also support an inhibitory role for the D3 receptor in regulating novelty-stimulated locomotion and suggest that individual variations in D3 receptor expression may underlie, at least in part, individual differences in reactivity to novelty.
Permanent Link: http://rave.ohiolink.edu/etdc/view?acc_num=ucin1088538631
http://hdl.handle.net/2374.OX/10550
Date: 2004

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