Françoise Dellu-Hagedorn

PubMed2006

Dimensional analysis of ADHD subtypes in rats.

BACKGROUND: Attention-deficit/hyperactivity disorder is a heterogeneous disorder that is classified into three subtypes in which the main symptoms, inattention, hyperactivity, and impulsivity, are expressed with various degrees of severity. The nature of the biological dysfunction sustaining each subtype (common or distinct) is unknown, and animal models encompassing different subtypes are needed. METHODS: A cluster analysis separated subgroups of rats on the basis of similarities in both impulsivity and attentional scores in the five-choice serial reaction time task. These subgroups were characterized behaviorally and were compared for several aspects of spontaneous hyperactivity in different environmental contexts. The dose effects of two agents used clinically (methylphenidate and atomoxetine) were tested on attention and impulsivity. RESULTS: Four distinct subgroups were demonstrated: efficient, middle, inattentive, and inattentive-impulsive. Hyperactivity expressed in a cage, characterized the last subgroup. Subgroups were differentially sensitive to environmental and pharmacologic challenges. Methylphenidate increased impulsivity mainly in the combined subgroup, whereas atomoxetine decreased impulsivity, neither with any effect on the efficient subgroup and on accuracy. CONCLUSIONS: This new approach is the first to demonstrate behavioral subtypes in rats that parallel those observed in human beings and is a promising tool to clarify the biological bases of these behavioral subtypes and to explain therapeutic effects.

Adrenergic Uptake Inhibitors↗

PubMed2006

Relationship between impulsivity, hyperactivity and working memory: a differential analysis in the rat.

BACKGROUND: Impulsivity is a behavioural trait that comprises several distinct processes. It is a key feature of many psychopathologies such as mania, addictive disorders or attention deficit-hyperactivity disorders. To date, the aspects of impulsiveness involved in these pathologies have not yet been explicitly defined. In these disorders, sensation or drug seeking and cognitive deficits are closely related, but the nature of these relationships remains largely unknown. A new animal model of impulsiveness based on spontaneous inter-individual differences is proposed here to help clarify the relationship between characteristic aspects of impulsive-related pathologies. METHODS: Rats were divided into sub-groups according to their scores in three operant tasks with varying degrees of behavioural inhibition, timing and motor vs. cognitive impulsivity demands. These tasks included a fixed consecutive number schedule (ability to complete an action to receive a reinforcer), a multiple fixed-interval/extinction schedule of reinforcement (high level of responding), and a delayed reward task (delay discounting). In addition, measurements of locomotor responses to novelty and to amphetamine in a circular corridor, and working memory in an 8-arm radial maze were obtained. RESULTS: Substantial behavioural inter-individual differences were observed in each task, whereas few inter-task relationships were found. Impulsive rats, as defined in a task requiring inhibition of premature responses, presented a higher increase in amphetamine-induced locomotion. Reduced working memory performance was only observed in hyperactive rats in an extinction schedule. CONCLUSION: This novel approach shows that distinct aspects of impulsiveness and hyperactivity can be expressed based on large inter-individual differences that vary from poorly to highly adapted behaviours ones in a normal population of rats. Inhibitory deficit was related to a higher response to psychostimulants a characteristic of rats predisposed to amphetamine self-administration and related to higher limbic dopaminergic activity, whereas working memory capacity was only related to hyperactivity. This approach allows for the identification of particular individuals presenting distinct behavioural characteristics of impulsive-related psychopathologies. These individuals may be of great interest in the modelling of these disorders and the exploration of their neurobiological bases.

Journal Article↗