A selective dopamine reuptake inhibitor improves prefrontal cortex-dependent cognitive function: potential relevance
Brooke E Schmeichel1, Frank P Zemlan, Craig W Berridge
1Psychology Department, University of Wisconsin, 1202 W. Johnson St., Madison, WI 53706, USA.
Neuropharmacology
|July 17, 2012
Summary
A novel benztropine analog, AHN 2-005, improved spatial working memory in rats, similar to ADHD medications. This compound selectively targets dopamine transporters but also increased norepinephrine and dopamine in the prefrontal cortex.
Area of Science:
- Neuroscience
- Pharmacology
- Cognitive Science
Background:
- Attention deficit hyperactivity disorder (ADHD) treatments enhance prefrontal cortex (PFC)-dependent cognition.
- Current ADHD medications include dual norepinephrine (NE) and dopamine (DA) reuptake inhibitors (psychostimulants) or selective NE reuptake inhibitors (SNRIs).
- Benztropine analogs offer selective DA reuptake inhibition without psychostimulant abuse potential.
Purpose of the Study:
- To evaluate the efficacy of the benztropine analog AHN 2-005 in treating ADHD.
- To assess AHN 2-005's effects on PFC-dependent spatial working memory in a rat model.
- To investigate the neurochemical mechanisms underlying AHN 2-005's cognitive-enhancing effects.
Main Methods:
- Rats were tested on a PFC-dependent delayed-alternation task for spatial working memory.
- AHN 2-005's effects on task performance were assessed dose-dependently.
- Microdialysis was used to measure extracellular DA and NE levels in the PFC and nucleus accumbens.
Main Results:
- AHN 2-005 dose-dependently improved performance on the spatial working memory task.
- Cognition-enhancing, non-locomotor activating doses of AHN 2-005 increased both DA and NE in the PFC.
- AHN 2-005 increased DA in the nucleus accumbens, but less than psychostimulants.
Conclusions:
- Benztropine analogs, like AHN 2-005, show potential for treating ADHD and other PFC dysfunction disorders.
- AHN 2-005 enhances cognitive function by increasing DA and NE in the PFC.
- Further research into AHN 2-005's mechanisms and clinical utility is warranted.
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