The effects of early life stress on impulsivity.

Elevated impulsivity is a symptom shared by various psychiatric disorders such as substance use disorder, bipolar disorder, and attention-deficit/hyperactivity disorder. However, impulsivity is not a unitary construct and impulsive behaviors fall into two subcategories: impulsive action and impulsive choice. Impulsive choice refers to the tendency to prefer immediate, small rewards over delayed, large rewards, whereas impulsive action involves difficulty inhibiting rash, premature, or mistimed behaviors. These behaviors are mediated by the mesocorticolimbic dopamine (DA) system, which consists of projections from the ventral tegmental area to the nucleus accumbens and prefrontal cortex. Early life stress (ELS) alters both impulsive choice and impulsive action in rodents. ELS also changes DA receptor expression, transmission, and activity within the mesocorticolimbic system. This review integrates the dopamine, impulsivity, and ELS literature to provide evidence that ELS alters impulsivity via inducing changes in the mesocorticolimbic DA system. Understanding how ELS affects brain circuits associated with impulsivity can help advance treatments aimed towards reducing impulsivity symptoms in a variety of psychiatric disorders.

Modulating chronic stress.

Social rank differentially influences how male and female mice respond to chronic stress.

The long-term effects of stress and kappa opioid receptor activation on conditioned place aversion in male and female California mice.

Psychosocial stress leads to the activation of kappa opioid receptors (KORs), which induce dysphoria and facilitate depression-like behaviors. However, less is known about the long-term effects of stress and KORs in females. We examined the long-term effects of social defeat stress on the aversive properties of KOR activation in male and female California mice (Peromyscus californicus) using a conditioned place aversion paradigm. Female California mice naïve to social defeat, formed a place aversion following treatment with 2.5mg/kg of the KOR agonist U50,488, but females exposed to defeat did not form a place aversion to this dose. This supports the finding by others that social defeat weakens the aversive properties of KOR agonists. In contrast, both control and stressed males formed an aversion to 10mg/kg of U50,488. We also examined EGR1 immunoreactivity, an indirect marker of neuronal activity, in the nucleus accumbens (NAc) and found that stress and treatment with 10mg/kg of U50,488 increased EGR1 immunoreactivity in the NAc core in females but reduced activation in males. The effects of stress and U50,488 on EGR1 were specific to the NAc, as we found no differences in the bed nucleus of the stria terminalis. In summary, our data indicate important sex differences in the long-term effects of stress and indicate the need for further study of the molecular mechanisms mediating the behavioral effects of KOR in both males and females.