Enhanced amphetamine-induced motor impulsivity and mild attentional impairment in the leptin-deficient rat model of obesity.

Evidence suggests that impulse control deficits contribute to excessive food intake in some individuals with obesity. In addition to its known role in regulating appetite and glucose metabolism, the hormone leptin also directly modulates the activity of central dopamine systems. Although dopamine is involved in regulating impulsivity, the influence of leptin per se on this cognitive domain remains unclear. This study explored the performance of male leptin knockout (KO) and wild type (WT) rats in the 5-Choice Serial Reaction Time task (5CSRTT) of motor impulsivity and visuospatial attention. Behavioural performance was assessed under baseline conditions, following 4 weeks high-fat diet (HFD; 60 kcal%) consumption, and after acute pharmacological challenge with the indirect dopamine agonist, amphetamine. Subjects were also tested for glucose tolerance and insulin sensitivity, and dorsal and ventral striatal tissue was assayed ex vivo for markers of dopaminergic transmission. Obese KO rats learned the 5CSRTT at a slower rate compared to WT rats, in a manner suggestive of mild attentional impairment. However, task performance at baseline and after HFD intake was similar to that of WT controls. HFD intake reduced omissions across all subjects, whereas amphetamine challenge revealed a prominent genotype effect on 5CSRTT performance, with potentiated levels of impulsive responding and faster response times in KO rats compared to WT animals. Effects of amphetamine on other variables were similar between genotypes. Notably, the expression of striatal dopaminergic markers was unchanged in KO rats, and neither chronic food restriction nor HFD intake altered the impairments in glucose or insulin metabolism previously reported in these animals. These data suggest that leptin deficiency enhances impulsive action under conditions of dopaminergic challenge, yet this seems independent of overt changes in the expression of post-synaptic markers of dopamine signalling in striatal regions.