Behavioral and Serotonergic Changes in the Frontal Cortex Following Methamphetamine Self-Administration

BACKGROUND: Methamphetamine use is associated with a variety of negative health outcomes, including psychosis. The frontal cortex serotonin receptors are thought to contribute to psychosis-like behaviors. This study investigated changes in serotonergic markers in the frontal cortex following methamphetamine self-administration and hallucinogenic drug-induced behavior. METHODS: Consistent with previously published studies, freely cycling male and female rats were allowed to self-administer methamphetamine (males: 0.12 mg/infusion; females: 0.09 mg/infusion) or saline (10 µL) for 7 days. On the day following self-administration or following 10 days of extinction training, animals were given the serotonin 2A/2C agonist, 1-(2,5-Dimethoxy-4-iodophenyl)-2-aminopropane hydrochloride (2 mg/kg, i.p.), and head twitches were analyzed. Autoradiography was also used to assess serotonin receptors and transporters in the frontal cortex following self-administration. RESULTS: Methamphetamine self-administration led to an increase in DOI-induced head-twitch behavior compared to saline only on the day following self-administration. Increases in serotonin receptors in the orbitofrontal cortex and decreases in serotonin transporters in the orbitofrontal cortex and infralimbic cortex were observed following methamphetamine self-administration as assessed by autoradiography. CONCLUSIONS: Methamphetamine self-administration was associated with serotonergic alterations in the frontal cortex, which may underlie behavioral changes related to methamphetamine-associated psychosis.