The Role of Serotonin in the Regulation of Patience and Impulsivity

Classic theories suggest that central serotonergic neurons are involved in the behavioral inhibition that is associated with the prediction of negative rewards or punishment. Failed behavioral inhibition can cause impulsive behaviors. However, the behavioral inhibition that results from predicting punishment is not sufficient to explain some forms of impulsive behavior. In this article, we propose that the forebrain serotonergic system is involved in “waiting to avoid punishment” for future punishments and “waiting to obtain reward” for future rewards. Recently, we have found that serotonergic neurons increase their tonic firing rate when rats await food and water rewards and conditioned reinforcer tones. The rate of tonic firing during the delay period was significantly higher when rats were waiting for rewards than for tones, and rats were unable to wait as long for tones as for rewards. These results suggest that increased serotonergic neuronal firing facilitates waiting behavior when there is the prospect of a forthcoming reward and that serotonergic activation contributes to the patience that allows rats to wait longer. We propose a working hypothesis to explain how the serotonergic system regulates patience while waiting for future rewards

Efeito do lítio sobre a hiperatividade locomotora induzida pela lesão eletrolítica da região do núcleo mediano da rafe em ratos Effect of lithium treatment on the locomotor hyperactivity induced by the lesion of the region of the median raphe nucleus in rats

A lesão do núcleo mediano da rafe (NMR) produz sintomas que sugerem validade de face ao episódio maníaco. Esta pesquisa avaliou o efeito do lítio sobre a hiperatividade locomotora induzida por esta lesão. Vinte e um ratos Wistar machos foram submetidos à lesão eletrolítica da região do NMR (LR) e 17 foram submetidos à lesão fictícia (LF). Após recuperação, a atividade locomotora foi avaliada na caixa de atividade (Med Associates/ENV-515). Parte dos animais destes grupos recebeu tratamentos com lítio (47,5 mg/kg/2x dia i.p.) por 10 dias, enquanto o restante foi tratado com salina no mesmo esquema. A reavaliação ao final dos tratamentos demonstrou que o lítio reduziu significantemente a atividade locomotora em relação à avaliação inicial no grupo LR (ANOVA/Bonferroni p < 0,05), tornando-a equivalente aos baixos níveis dos grupos LF. Estes dados sustentam a hipótese de que as manifestações induzidas pela lesão do NMR podem constituir um modelo animal de mania.<br>The lesion of the Median Raphe Nucleus (MRN) produces symptoms that suggest face validity for manic episodes. This research evaluated the effect of lithium treatment on the locomotor hyperactivity induced by this lesion. Twenty-one Wistar male rats were submitted to the lesion of the region of the MRN (LR) and 17 were sham lesioned (LF). After recovery, the locomotor activity was evaluated in an activity chamber (Med Associates/ENV-515). A subgroup received lithium (47.5 mg/kg/twice a day i.p.) for 10 days, while the other animals received saline in the same schedule. The reevaluation at the end of the treatments showed that only lithium significantly reduced the activity of LR group compared to baseline levels (ANOVA/Bonferroni p < 0.05), making it equivalent to low levels of LF groups. These data support the hypothesis that the behavioral manifestations induced by the lesion of the MRN may constitute an animal model of mania

Methylphenidate administration to adolescent rats determines plastic changes on reward-related behavior and striatal gene expression

Administration of methylphenidate (MPH, Ritalins) to children with attention deficit hyperactivity disorder (ADHD) is an elective therapy, but raises concerns for public health, due to possible persistent neurobehavioral alterations. Wistar adolescent rats (30 to 46 day old) were administered MPH or saline (SAL) for 16 days, and tested for reward-related and motivational-choice behaviors. When tested in adulthood in a drug-free state, MPH-pretreated animals showed increased choice flexibility and economical efficiency, as well as a dissociation between dampened place conditioning and more marked locomotor sensitization induced by cocaine, compared to SALpretreated controls. The striatal complex, a core component of the natural reward system, was collected both at the end of the MPH treatment and in adulthood. Genome-wide expression profiling, followed by RT-PCR validation on independent samples, showed that three members of the postsynaptic-density family and five neurotransmitter receptors were upregulated in the adolescent striatum after subchronic MPH administration. Interestingly, only genes for the kainate 2 subunit of ionotropic glutamate receptor (Grik2, also known as KA2) and the 5-hydroxytryptamine (serotonin) receptor 7 (Htr7) (but not GABAA subunits and adrenergic receptor a1b) were still upregulated in adulthood. cAMP responsive element-binding protein and Homer 1a transcripts were modulated only as a long-term effect. In summary, our data indicate short-term changes in neural plasticity, suggested by modulation of expression of key genes, and functional changes in striatal circuits. These modifications might in turn trigger enduring changes responsible for the adult neurobehavioral profile, that is, altered processing of incentive values and a modified flexibility/habit balance