Potential programming of dopaminergic circuits by early life stress

Abstract

Stress and high levels of glucocorticoids during pre- and early postnatal life seem to alter developmental programs that assure dopaminergic transmission in the mesolimbic, mesocortical, and nigrostriatal systems. The induced changes are likely to be determined by the ontogenetic state of development of these brain regions at the time of stress exposure and their stability is associated with increased lifetime susceptibility to psychiatric disorders, including drug addiction. This article is intended to serve as a starting point for future studies aimed at the attenuation or reversal of the effects of adverse early life events on dopamine-regulated behaviors.

Mechanisms of initiation and reversal of drug-seeking behavior induced by prenatal exposure to glucocorticoids

“…Furthermore, the dopaminergic system seems particularly sensitive to the effects of GCs (5,12,30). Thus, we next data not shown), the NAcc is seemingly most sensitive to the effects of prenatal GC.…”

“…CPP was assessed on day 5 (20 min) when all compartments were accessible to the animal. Results are expressed as the difference of 5 time spent in the drug-paired and saline-paired side.…”

“…The programming effects of stress are most likely mediated by endogenous glucocorticoids (GC) whose ability to produce structural re-organization and dysfunction of the neural substrates that underpin these stress-related pathologies are well known (1,(5)(6)(7). Although administration of prenatal GC does not mimic prenatal stress, synthetic GC such as dexamethasone (DEX) are widely used in obstetrics, e.g.…”

Early life stress and psychopharmacology

“…From the developmental perspective, Rudolph et al (2010) present a study showing how individual differences in stress sensitivity shape the clinical response to peer victimization in children. This is mirrored in the preclinical arena, with findings that animals exposed to ELS are affected in their response to drugs of abuse (Rodrigues et al 2010), cognitive function (Hedges and Woon 2010;Oomen et al 2010), anxiety-related behaviors (Peleg-Raibstein and Feldon 2010), depression-and psychosis-related behaviors (Markham and Koenig 2010), stress sensitivity and hypothalamic-pituitary-adrenal (HPA) axis function (Claessens et al 2010), and sleep (Pryce et al 2010), as well as in the brain-gut axis (modeling aspects of irritable bowel syndrome) (O'Mahony et al 2010). Certainly, limitations to these models do exist (Schmidt et al 2010;Van Waes et al 2010), reflecting a variety of individual differences (Claessens et al 2010), including whether animals are tested during adolescence or adulthood (Peleg-Raibstein and Feldon 2010).…”

“…Matsuzaki et al (2010) and Groenink et al (2010) investigate the role of 5-HT1A receptors in fear conditioning, and startle reactivity and prepulse inhibition, respectively. Rodrigues et al (2010) review the effects of ELS on the function of the dopaminergic system. Moreover, it becomes increasingly obvious that perinatal exposure to pharmacological stressors, such as alcohol (Marche et al 2010) or cannabinoids (Campolongo et al 2010), can be conceptualized as ELS, accompanied by altered stress sensitivity, motor, cognitive, and emotional function later on in life.…”