1 Consequences of Serotonin Transporter Depletion on Amphetamine Intake – A behavioural Analysis

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BACKGROUND: Psychostimulant abuse is a major societal burden. Stimulants such as amphetamine (AMPH) act on the monoaminergic systems, including the serotonin transporter (SERT). Serotonin (5- hydroxytryptamine, 5-HT) has been implicated in the development of AMPH addiction and a reduced expression of SERT is associated with higher psychostimulant intake in both humans and rats. Moreover, brain-derived neurotrophic factor (BDNF) and corticotropin-releasing factor (CRF) are known to be involved in psychostimulant abuse. We aim to give insights into the role of SERT in moderate and compulsive AMPH intake and the accompanying changes in BDNF and CRF protein levels. METHODS: Serotonin transporter knockout (SERT KO) and wildtype (SERT WT) rats were subjected to either short access (ShA, 1hour) or long access (LgA, 6hours) AMPH self-administration followed by a progressive ratio test. Western Blot protocols of brain punches of the paraventricular nucleus of the hypothalamus (PVN) and the central nucleus of the amygdala (CeA) have been set-up. RESULTS: AMPH self-administration was increased in SERT KO rats as compared to SERT WT animals in the LgA condition. No differences between SERT KO and SERT WT were found during ShA selfadministration. The progressive ratio test revealed no differences between animals of the two genotypes in either access condition. Western Blot procedures have been validated. LgA-induced changes in CRF and BDNF protein expression have to be analysed in the future. CONCLUSIONS: SERT KO animals are more prone to escalate drug intake under extended, but not short access to amphetamine. This might have implications for humans carrying the short allelic serotonin transporter-linked polymorphism with a long drug history.
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