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A General Method for Evaluating Deep Brain Stimulation Effects on Intravenous Methamphetamine Self-Administration

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Published on: January 22, 2016

Perseverative behavior in rats with methamphetamine-induced neurotoxicity.

Jong-Hyun Son¹, James Kuhn, Kristen A Keefe

¹Department of Pharmacology and Toxicology, 30 S. 2000 E., Rm 201, University of Utah, Salt Lake City, UT 84112, USA.

Neuropharmacology

|November 20, 2012

Summary

Methamphetamine neurotoxicity in rats caused perseverative behaviors, impacting their ability to switch tasks. This suggests frontal cortex serotonin may influence behavioral flexibility after drug exposure.

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Area of Science:

Neuroscience
Behavioral Pharmacology
Toxicology

Background:

Methamphetamine use leads to monoamine depletions, linked to cognitive and behavioral deficits.
Previous research indicated methamphetamine neurotoxicity impairs stimulus-response association formation.
Subjective observations suggested potential deficits in behavioral flexibility.

Purpose of the Study:

To investigate if methamphetamine neurotoxicity induces perseverative behavior in rats.
To examine the relationship between methamphetamine-induced monoamine depletions and behavioral flexibility.

Main Methods:

Rats were pretreated with methamphetamine or saline and later trained on an operant conditioning task.
Performance was assessed over four consecutive sessions at criterion level.

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Brain monoamine levels, specifically dopamine and serotonin, were determined post-experiment.

Main Results:

Methamphetamine-pretreated rats exhibited a ~50% loss of striatal dopamine and prefrontal serotonin.
No differences were observed in task acquisition or total lever presses.
Methamphetamine-treated rats earned fewer rewards due to perseverative lever pressing and slower behavioral switching.

Conclusions:

Partial monoamine toxicity from methamphetamine is associated with perseverative behavior.
The degree of perseveration negatively correlated with prefrontal cortex serotonin transporter binding.
Serotonin innervation of the frontal cortex may play a role in regulating behavioral flexibility after methamphetamine exposure.