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

ABSTRACT: Methamphetamine (METH) use is associated with a variety of negative health outcomes including psychosis. The frontal cortex serotonin (5-HT)-2 receptors are thought to contribute to psychosis-like behaviors. This study investigated changes in serotonergic markers in the frontal cortex following METH self-administration and hallucinogenic drug-induced behavior.Consistent with previously published studies, freely-cycling male and female rats were allowed to self-administer METH (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 d of extinction training, animals were given the 5-HT2A/2C agonist, DOI (2 mg/kg, i.p.), and head-twitches were analyzed.METH self-administration lead to an increase in DOI-induced head-twitch behavior compared to saline only on the day following self-administration. Increases in 5-HT2 receptors in the orbitofrontal cortex and decreases in 5-HT transporters in the orbitofrontal cortex and infralimbic cortex were observed following METH self-administration as assessed by autoradiography.Methamphetamine self-administration was associated with serotonergic alterations in the frontal cortex which may underlie behavioral changes related to METH-associated psychosis.

SUBMITTER: McFadden LM

PROVIDER: S-EPMC6070086 | biostudies-other | 2018 May

REPOSITORIES: biostudies-other

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

McFadden Lisa M LM Cordie Rebecca R Livermont Tamee T Johansen Andrew A

The international journal of neuropsychopharmacology 20180801 8

<h4>Background</h4>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.<h4>Methods</h4>Consistent with previously published studies, freely cycling male and female rats were allowed to self-admi ...[more]

PMID: 29762664

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Project description:BACKGROUND:Although hair testing is well established for the assessment of past drug exposure, uncertainties persist about mechanisms of drug incorporation into hair and interpretation of results. The aim of this study was to administer methamphetamine (MAMP) under controlled conditions as a model drug to investigate drug incorporation into human hair. MATERIAL AND METHODS:Seven volunteers with a history of stimulant use received 4×10 mg (low) doses of sustained release S-(+)-MAMP HCl within 1 week, with weekly head hair samples collected by shaving. 3 weeks later, 4 of them received 4×20 mg (high) doses. After extensive isopropanol/phosphate buffer washing of the hair, MAMP and its metabolite amphetamine (AMP) concentrations were determined in all weekly hair samples by LC-MS-MS in selected reaction monitoring mode with the undeca- and deca-deuterated drugs, respectively, as internal standards (LLOQ, 0.005 ng mg(-1)). RESULTS:MAMP T(max) occurred from 1 to 2 weeks after both doses, with C(max) ranging from 0.6 to 3.5 ng mg(-1) after the low and 1.2 to 5.3 ng mg(-1) after the high MAMP doses. AMP C(max) in hair was 0.1-0.3 ng mg(-1) and 0.2-0.5 ng mg(-1), respectively, for low and high doses. Highly dose-related concentrations within subjects, but large variability between subjects were observed. MAMP concentrations were above the 0.2 ng mg(-1) cut-off for at least 2 weeks following administration of both low and high doses. The overall AMP/MAMP ratio ranged from 0.07 to 0.37 with a mean value of 0.15 ± 0.07, and a median of 0.13. The percentage of MAMP and AMP removed with the washing procedure decreased with time after administration. A strong correlation was found between area under the curve of MAMP (r(2)=0.90, p=0.00) and AMP (r(2)=0.94, p=0.00) concentrations calculated for the 3-week period following administration and the total melanin concentration in hair. Significant correlations were observed also between C(max) and melanin. CONCLUSIONS:This study demonstrated that despite large inter-individual differences, the incorporation of MAMP and AMP into hair is dose-related with much of the observed scatter of MAMP and AMP concentrations explained by melanin concentration in hair.

Dataset Information

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

Publications

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

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