Sensitivity to Amphetamine Depends on a lack of Serotonin Transporters
Keywords
No Thumbnail Available
Authors
Issue Date
2016-07-01
Language
en
Journal Title
Journal ISSN
Volume Title
Publisher
Abstract
Background: Amphetamine abuse is a worldwide problem. Serotonin and dopamine are important neurotransmitters which are implicated in the acquisition, maintenance and relapse phase of amphetamine addiction. By blocking and reversing the action of dopamine reuptake transporters and reversing the action of serotonin reuptake transporters, amphetamine increases extracellular dopamine and serotonin levels. The present study aims to give insights in the role of the serotonin transporter and accumbal serotonin in amphetamine reward and addiction by combining microdialysis and behavioural testing in serotonin transporter knock out rats (SERT KO) and their wildtype (SERT WT) counterparts.
Method: SERT KO and SERT WT were subjected to an acute amphetamine challenge (2.5 mg/kg) while locomotor activity, ultrasonic vocalizations and extracellular serotonin and dopamine levels were measured in the nucleus accumbens shell. A separate cohort of SERT KO and SERT WT was subjected to amphetamine self-administration (0.03 mg/kg/infusion) followed by a progressive ratio test to measure motivation.
Results: Microdialysis revealed an increase of both serotonin and dopamine levels after amphetamine (2.5 mg/kg) administration, but no significant genotype differences were found. However, the increase in extracellular accumbal serotonin, but not dopamine levels of SERT KO animals was more prolonged. SERT KO rats emitted more 50 kHz ultrasonic vocalizations and had higher locomotor activity compared to SERT WT rats after amphetamine. Self-administration revealed that SERT KO rats self-administered more amphetamine (0.03 mg/kg/infusion) compared to SERT WT rats. SERT KO animals showed a quadratic increase in their intake, whereas SERT WT showed a linear increase in their intake. Furthermore, SERT KO scored higher on the progressive ratio test.
Discussion and conclusion: All our results linked together support the hypothesis that SERT KO rats are more sensitive to amphetamine, which may lead to an increased intake compared to SERT WT rats. Accumbal dopamine levels did not differ between the genotypes, which may imply an important role for accumbal serotonin in individual differences in drug reward and sensitivity. While being careful in generalizing to humans, our findings could have implications for individualized treatments for patients with amphetamine addiction.
Description
Citation
Supervisor
Faculty
Faculteit der Sociale Wetenschappen