Abstract
Impulsivity, poorly conceived or prematurely executed behavior, is an important characteristic of human personality, but to some people, impulsivity is debilitating. They are unable to maintain jobs or friends. In this thesis, we study the differences and similarities of two different types of impulsivity. The first is a deficit of
... read more
response inhibition: an inability to inhibit planned or ongoing behavior. The second is delay aversion: an intolerance to delays to rewards. The aim of this thesis was to uncover differences and similarities between these types of behavior, and to find putative anti-impulsive drugs. The research consisted of three parts. In the first, we investigated the induction of both types of impulsivity in rats. In the second, we studied the relationship between baseline levels of impulsivity to several other types of behavior: locomotor activity, extinction learning, aggressive behavior, and sexual behavior in rats, and addictive behavior in human subjects. In the final part, we set out to find novel pharmacological strategies for the treatment of both types of impulsivity. We learned that social isolation in rats could lead to both a deficit of response inhibition and delay aversion, although the latter emerges only after a number of months. Administration of D-amphetamine lowered delay aversion and worsened response inhibition, in particular in isolated animals. Pre-existing (not-induced) differences in levels of delay aversion and response inhibition in rats were strongly related to extinction learning and aggressive behavior, but not locomotor activity and sexual behavior. In humans, delay aversion was found to be associated to addictive behaviors, in particular to smoking. These relationships suggested that known pharmacological targets for decreasing aggression, addiction, and extinction speed may also lower delay aversion. To that end, the effects of several psychoactive drugs on delay aversion of rats were tested. The results indicated that the dopamine D3-receptor, and in particular the serotonin 5-HT1A-receptor may be interesting targets for the treatment of impulsivity. Therefore, we tested the effects of the anti-aggressive drug eltoprazine (a serotonin 5-HT1A/1B-receptor agonist) on delay aversion and response inhibition and compared those effects to the effects of D-amphetamine. Both eltoprazine and D-amphetamine lowered delay aversion, but increased response inhibition failures. Local measurements in the brain suggested that the effects of eltoprazine were not due to changes in dopamine levels. Rather, changes in serotonin levels were hypothesized to be involved. This finding suggests that the mechanism by which eltoprazine affects impulsivity subtypes is very different from that of D-amphetamine, and could be of potential value in the treatment of psychiatric disorders in which impulsivity plays an important role.
show less