Chemogenetic tools for modulation of spatial learning in dopamine transporter deficient rats
Abstract
Objectives We used the chemogenetic tools for the activation of norepinephrine (NE) release in the prefrontal cortex (PFC) of dopamine transporter knockout (DAT-KO) rats. The objective of this study was to evaluate the effect of chemogenetic activation of NE release in the PFC on the performance of a spatial behavior task by DAT-KO rats. The rats DAT-KO rats with deletion of DAT gene were created as a valuable model for persistently elevated extracellular DA levels. The DAT-KO rats show marked behavioral abnormalities: impulsivity, stereotypy and reduced learning ability. Such hyperdopaminergia is thought to be one of the causes of disorders such as schizophrenia, mania and attention deficit hyperactivity disorder (ADHD). The Locus Coeruleus (LC) is a critical area in the brain that plays an important role in control of several physiological and behavioral processes due to the existence of extensive connections to cortical and subcortical structures. Its activity can modulate both norepinephrine and dopamine neurotransmission, particularly in the PFC. Materials and methods We used canine adenovirus type 2 (CAV2) to selectively activate LC-NA neurons in DAT-KO rats. The chemogenetic modulation of spatial learning in knockout and wild-type (WT) rats was tested in the Hebb-Williams maze. Variables such as the distance traveled, time taken to reach the goal box, number of errors and the perseverative patterns of activity were analyzed. Results Norepinephrine release from the LC…
Read the paper
Related studies
- The neurocircuitry of addiction: an overview
- Gender Differences in Human Brain: A Review
- Stratified medicine for mental disorders
- The neurobiology of drug addiction: cross-species insights into the dysfunction and recovery of the prefrontal cortex
- Annual Research Review: DNA methylation as a mediator in the association between risk exposure and child and adolescent psychopathology
- Schizophrenia: The new etiological synthesis
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.