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Methamphetamine‐Induced Changes to Serotonergic Markers in the Frontal Cortex

Methamphetamine use is associated with a variety of negative health outcomes including psychosis. Alternations in the frontal cortex including changes in serotonin (5HT) 2A receptors are thought to contribute to psychosis‐like behaviors. Previously we have reported that methamphetamine self‐administration changes serotonin in the frontal cortex of rats. The purpose of this study was to investigate changes in serotonergic markers in the frontal cortex following methamphetamine self‐administration and how these changes relate to hallucination‐like behavior. Male and female rats were allowed to self‐administer either methamphetamine or saline and were sacrificed either one hour after the last self‐administration session or following extinction training. Serotonin transporters (SERT) and 5HT2A receptors were assessed in the frontal cortex via autoradiography. No changes in SERT autoradiography was observed in the orbitofrontal, prelimbic, or infralimbic cortices one hour after self‐administration or after extinction training. However, preliminary findings suggest time dependent changes in 5HT2A receptors in the frontal cortex. One hour after the last self‐administration session 5HT2A receptors were increased in the orbitofrontal cortex. Further, there was a trend towards an increase in prelimbic 5HT2A receptors in rats that self‐administered methamphetamine. However, no changes were found in male rats following extinction training. To assess the functioning of the 5HT2A receptors, the 5HT2A/2C agonist, DOI, was administered in a separate group of animals following extinction training. Preliminary results suggest that rats with a history of METH self‐administration have reduced hyperthermia following the administration of DOI. Efforts are underway to quantify DOI‐induced head twitches which are thought to reflect 5HT2A receptor function in the brain and hallucination‐like behavior. Overall, results of the current study suggest that methamphetamine self‐administration causes time dependent changes in 5HT2A receptors but not SERT in the frontal cortex. Ongoing studies will examine how methamphetamine‐induced changes in the frontal cortex may result in changes in behaviors associated with psychosis such as hallucinations.