Archival ReportPharmacologic Rescue of Motivational Deficit in an Animal Model of the Negative Symptoms of Schizophrenia
Section snippets
Mice
The generation of D2R-OE mice, temporal regulation of the transgene, and food restriction protocol have been previously described (6) and are detailed in Supplement 1.
Behavior Testing
Behavioral testing was carried out as previously described for progressive ratio (8, 10), with some adjustments. For a detailed description of the apparatus and procedures used, please see outline and text in Supplement 1.
Drug Treatments
The 5-HT2C receptor antagonist SB24280 (Sigma Aldrich, St. Louis, Missouri) was dissolved in .9% saline and
Selective Overexpression of Dopamine D2 Receptors in Striatum Results in a Reversible Impairment in Incentive Motivation Across a Range of Work Requirements and Is Not Due to a Difference in Sensitivity to Satiety or Fatigue
We previously determined that mice with striatal specific overexpression of D2Rs display a reversible impairment in incentive motivation (8, 10). Using a doubling operant progressive ratio schedule (PR X2), we found that D2R-OE mice earned significantly fewer rewards than control littermates. This phenotypic difference was reversible; it was eliminated by doxycycline, which switched off the expression of the transgene. To determine if this genotypic difference was consistent for less onerous
Discussion
Two characteristic features of schizophrenia are deficits in incentive motivation and in cognition, each of which negatively impacts the other (22). Both of these features are evident in D2R-OE mice. We find that the transient motivational deficit observed in the D2R-OE mice is due to a reluctance to work for food, rather than a decrease in satiation threshold, a decreased tolerance for low rates of reward, or a difference in reactivity to reward itself. Systemic pharmacologic blockade of D2Rs
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Maternal immune activation alters sensitivity to action-outcome contingency in adult rat offspring
2017, Brain, Behavior, and ImmunityCitation Excerpt :Motivational impairments could arise due to an inability to experience pleasure (anhedonia) or an inability or unwillingness to work purposefully to obtain a rewarding outcome (avolition) (Barnes et al., 2014; Gard et al., 2007). Research in both human participants (Cohen and Minor, 2010; Gold et al., 2008) and with animal models of schizophrenia favours the latter idea (Simpson et al., 2011). For example, Ward et al. (2012) used a transgenic animal model of the negative symptoms of schizophrenia in which mice over-express striatal dopamine (DA) D2 receptors (D2R-OE mice).
The Neurobiology of Activational Aspects of Motivation: Exertion of Effort, Effort-Based Decision Making, and the Role of Dopamine
2024, Annual Review of Psychology
Authors EHS and CK contributed equally to this work.