Dataset Information

Loss of dendrite stabilization by the Abl-related gene (Arg) kinase regulates behavioral flexibility and sensitivity to cocaine.

ABSTRACT: Adolescence is characterized by increased vulnerability to developing neuropsychiatric disorders and involves a period of prefrontal cortical dendritic refinement and synaptic pruning that culminates in cytoskeletal stabilization in adulthood. The Abl-related gene (Arg) acts through p190RhoGAP to inhibit the RhoA GTPase and stabilize cortical dendritic arbors beginning in adolescence. Cortical axons, dendrites, and synapses develop normally in Arg-deficient (arg(-/-)) mice, but adult dendrites destabilize and regress; thus, arg(-/-) mice present a model of adolescent-onset dendritic simplification. We show that arg(-/-) mice are impaired in a reversal task and that deficits are grossly exacerbated by low-dose cocaine administration. Although ventral prefrontal dopamine D2 receptor levels predict "perseverative" error counts in wild-type mice, no such relationship is found in arg(-/-) mice. Moreover, arg(-/-) mice are insensitive to the disruptive effects of the D2/D3 antagonist haloperidol in reversal but show normal sensitivity to its locomotor-depressant actions. Arg deficiency and orbitofrontal cortical Arg inhibition via STI-571 infusion also enhance the psychomotor stimulant actions of cocaine. These findings provide evidence that stabilization of dendritic structure beginning in adolescence is critical for the development of adaptive and flexible behavior after cocaine exposure.

SUBMITTER: Gourley SL

PROVIDER: S-EPMC2742404 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:Depressive symptoms and binge eating are both prevalent in weight management populations and may be associated with reduced benefit from behavioral weight loss, including higher attrition, more perceived barriers, lower weight loss, and increased weight regain. These two potential risk factors for poor behavioral weight loss outcomes may also be associated with each other as depressive symptoms may trigger binge eating, and binge eating-related distress could increase depressive symptoms. The depressive symptom-binge eating link has not been well studied in weight management samples, and psychological processes involved in this relationship have not yet been elucidated. Psychological flexibility, an individual's ability to be connected with and conscious of the present moment and to engage in values-consistent behavior even in the presence of difficult internal experiences, may be one psychological process that changes the depressive symptom-binge eating relationship. High psychological flexibility may be a protective factor in the association of depressive symptoms with binge eating. This study examined the relationship between depressive symptom and binge eating and a potential interactive role of psychological flexibility. Participants (N = 468, 76% female) completed self-report questionnaires of binge eating, depressive symptoms, and psychological flexibility at baseline prior to initiating behavioral weight loss. Depressive symptoms were positively associated with binge eating (B = 1.00, p < 0.001). Psychological flexibility had an interactive role (B = -0.03, p = 0.005). Among participants with minimal to mild depressive symptoms, those with higher psychological flexibility had less severe binge eating. Findings suggest that psychological flexibility may be a protective factor in the association between depressive symptoms and binge eating in the majority of individuals initiating behavioral weight loss. Psychological flexibility is a psychological process to consider targeting for enhancing efficacy of weight loss treatment, especially among individuals with minimal to mild depressive symptoms and binge eating behavior.

Dataset Information

Loss of dendrite stabilization by the Abl-related gene (Arg) kinase regulates behavioral flexibility and sensitivity to cocaine.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure