Concurrent activation of dopamine D1 and D2 receptors is required to evoke neural and behavioral phenotypes of cocaine sensitization

Repeated exposure to psychomotor stimulants produces a striking behavioral syndrome involving repetitive, stereotypic behaviors that occur if an additional exposure to the stimulant is experienced. The same stimulant exposure produces specific alterations in gene expression patterns in the striatum. To identify the dopamine receptor subtypes required for the parallel expression of these acquired neural and behavioral responses, we treated rats with different D1-class and D2-class dopamine receptor agonists and compared the responses of drug-naive rats with those of rats given previous intermittent treatment with cocaine. In rats exposed to repeated cocaine treatment, the effects of a subsequent challenge treatment with either a D1-class agonist (SKF 81297) or a D2-class agonist (quinpirole) were not significantly different from those observed in drug-naive animals: the drugs administered singly did not induce robust stereotyped motor behaviors nor produce significantly striosome-predominant expression of early genes in the striatum. In contrast, challenge treatment with the D1-class and D2-class agonists in combination led to marked and correlated increases in stereotypy and striosome-predominant gene expression in the striatum. Thus, immediately after repeated psychomotor stimulant exposure, only the concurrent activation of D1 and D2 receptor subclasses evoked expression of the neural and behavioral phenotypes acquired through repeated cocaine exposure. These findings suggest that D1-D2 dopamine receptor synergisms underlie the coordinate expression of both network-level changes in basal ganglia activation patterns and the repetitive and stereotypic motor response patterns characteristic of psychomotor stimulant sensitization.

Cross-reactions vs co-sensitization evaluated by in silico motifs and in vitro IgE microarray testing

Using an in silico allergen clustering method, we have recently shown that allergen extracts are highly cross-reactive. Here we used serological data from a multi-array IgE test based on recombinant or highly purified natural allergens to evaluate whether co-reactions are true cross-reactions or co-sensitizations by allergens with the same motifs.

Electrophysiological and behavioral correlates of stable automatic semantic retrieval in aging

Previous studies have shown both declining and stable semantic-memory abilities during healthy aging. There is consistent evidence that semantic processes involving controlled mechanisms weaken with age. In contrast, results of aging studies on automatic semantic retrieval are often inconsistent, probably due to methodological limitations and differences. The present study therefore examines age-related alterations in automatic semantic retrieval and memory structure with a novel combination of critical methodological factors, i.e., the selection of subjects, a well-designed paradigm, and electrophysiological methods that result in unambiguous signal markers. Healthy young and elderly participants performed lexical decisions on visually presented word/non-word pairs with a stimulus onset asynchrony (SOA) of 150 ms. Behavioral and electrophysiological data were measured, and the N400-LPC complex, an event-related potential component sensitive to lexical-semantic retrieval, was analyzed by power and topographic distribution of electrical brain activity. Both age groups exhibited semantic priming (SP) and concreteness effects in behavioral reaction time and the electrophysiological N400-LPC complex. Importantly, elderly subjects did not differ significantly from the young in their lexical decision and SP performances as well as in the N400-LPC SP effect. The only difference was an age-related delay measured in the N400-LPC microstate. This could be attributed to existing age effects in controlled functions, as further supported by the replicated age difference in word fluency. The present results add new behavioral and neurophysiological evidence to earlier findings, by showing that automatic semantic retrieval remains stable in global signal strength and topographic distribution during healthy aging.