Haplo-Insufficiency or Knockout of the Serotonin Transporter Does not Affect Heroin Self-Administration but Decreases BDNF in the Frontal Cortex

Abstract

(1) Background: Drug addiction places a heavy burden on those affected by it but only a small percentage of individuals (~20%), regardless of their drug of abuse, go on to develop the compulsive behaviours that define drug addiction. Clinical studies have shown that genetic variations that reduce serotonin transporter (SERT) activity increase the vulnerability to developing a variety of psychiatric disorders such as depression, anxiety and drug addiction. (2) Methods: To investigate the influence of reduced SERT function in the laboratory, we studied the effects of heroin self-administration in a SERT knockout rat model. Groups of homozygous knockout (HOM), heterozygous (HET) or wild type (WT) animals completed a series of heroin self-administration experiments. In addition, quantitative reverse transcription polymerase chain reaction was used to measure relative abundance of brain derived neurotrophic factor (BDNF) transcripts of in the frontal cortex and striatum in animals that had previously self-administered heroin. (3) Results: There were no differences between the genotypes for acquisition, maintenance and progressive ratio responding for heroin self-administration. However, relative expression of total BDNF and the BDNF III and BDNF VI isoforms were significantly decreased in the frontal cortex of animals that had self-administered heroin for all genotypes, however, no differences in BDNF expression were found in RNA isolated from the striatum relative to untreated control animals. (4) Conclusions: These data suggest that reduced SERT function does not augment the addictive properties of heroin and support the hypothesis that different classes of addictive substances act through different neurobiological pathways.