Synergistic enhancement of the acoustic startle reflex by dopamine D1 and 5-HT1A agonists and corresponding changes in c-Fos expression in the dorsal raphe of rats.

RATIONALE AND
OBJECTIVES: Several studies have reported an increase in dopamine (DA)-stimulated behavioral responses after manipulations that reduce brain serotonin (5-hydroxytryptamine, 5-HT) levels. Because others have shown that systemic administration of the 5-HT1A agonist 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT) reduces 5-HT levels throughout the brain, we tested the effects of 8-OH-DPAT on the enhancement of the acoustic startle reflex by the dopamine D1 receptor agonist SKF 82958. In addition, we used the expression of the c-Fos protein as a marker of neuronal activity to assess any corresponding drug-induced changes within the dorsal raphe (DR). METHODS AND
RESULTS: Male Sprague-Dawley rats pretreated (10 min) with 8-OH-DPAT (0.5 mg/kg) showed a marked potentiation of the enhancement of startle by SKF 82958 (0.1 mg/kg). Furthermore, SKF 82958 produced a dramatic induction of c-Fos in the DR, an effect that was blocked by 8-OH-DPAT. Double-labeling immunohistochemistry for c-Fos and 5-HT showed that SKF 82958-induced expression of c-Fos, and its blockade by 8-OH-DPAT, occurred in a percentage of 5-HT-containing cells of the DR.
CONCLUSIONS: These data suggest the possibility that inhibition of the DR by 8-OH-DPAT mediates the potentiation of startle by SKF 82958, perhaps through a reduction in 5-HT release in the striatum. Such an interpretation is consistent with the hypothesis of an inhibitory role of the 5-HT system on DA-mediated behaviors.