Ethanol self-administration in serotonin transporter knockout mice: unconstrained demand and elasticity

Abstract

<jats:p><jats:bold>Low serotonin function is associated with alcoholism, leading to speculation that increasing serotonin function could decrease ethanol consumption. Mice with one or two deletions of the serotonin transporter (<jats:styled-content style="fixed-case">SERT</jats:styled-content>) gene have increased extracellular serotonin. To examine the relationship between <jats:styled-content style="fixed-case">SERT</jats:styled-content> genotype and motivation for alcohol, we compared ethanol self‐administration in mice with zero (knockout, <jats:styled-content style="fixed-case">KO</jats:styled-content>), one (<jats:styled-content style="fixed-case">HET</jats:styled-content>) or two copies (<jats:styled-content style="fixed-case">WT</jats:styled-content>) of the <jats:styled-content style="fixed-case">SERT</jats:styled-content> gene. All three genotypes learned to self‐administer ethanol. The <jats:styled-content style="fixed-case">SSRI</jats:styled-content>, fluvoxamine, decreased responding for ethanol in the <jats:styled-content style="fixed-case">HET</jats:styled-content> and <jats:styled-content style="fixed-case">WT</jats:styled-content>, but not the <jats:styled-content style="fixed-case">KO</jats:styled-content> mice. When tested under a progressive ratio schedule, <jats:styled-content style="fixed-case">KO</jats:styled-content> mice had lower breakpoints than <jats:styled-content style="fixed-case">HET</jats:styled-content> or <jats:styled-content style="fixed-case">WT</jats:styled-content>. As work requirements were increased across sessions, behavioral economic analysis of ethanol self‐administration indicated that the decreased breakpoint in <jats:styled-content style="fixed-case">KO</jats:styled-content> as compared to <jats:styled-content style="fixed-case">HET</jats:styled-content> or <jats:styled-content style="fixed-case">WT</jats:styled-content> mice was a result of lower levels of unconstrained demand, rather than differences in elasticity, i.e. the proportional decreases in ethanol earned with increasing work requirements were similar across genotypes. The difference in unconstrained demand was unlikely to result from motor or general motivational factors, as both <jats:styled-content style="fixed-case">WT</jats:styled-content> and <jats:styled-content style="fixed-case">KO</jats:styled-content> mice responded at high levels for a 50% condensed milk solution. As elasticity is hypothesized to measure essential value, these results indicate that <jats:styled-content style="fixed-case">KO</jats:styled-content> value ethanol similarly to <jats:styled-content style="fixed-case">WT</jats:styled-content> or <jats:styled-content style="fixed-case">HET</jats:styled-content> mice despite having lower break points for ethanol</jats:bold>.</jats:p>