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

Psychopharmacology (Berl). 2000 Sep;151(4):359-67. doi: 10.1007/s002130000474.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 8-Hydroxy-2-(di-n-propylamino)tetralin / pharmacology
  • Animals
  • Benzazepines / pharmacology
  • Dopamine Agonists / pharmacology*
  • Drug Synergism
  • Immunohistochemistry
  • Male
  • Raphe Nuclei / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Dopamine D1 / agonists*
  • Receptors, Serotonin / drug effects*
  • Receptors, Serotonin, 5-HT1
  • Reflex / drug effects*
  • Reflex, Startle / drug effects*
  • Serotonin / analysis
  • Serotonin Receptor Agonists / pharmacology*


  • Benzazepines
  • Dopamine Agonists
  • Receptors, Dopamine D1
  • Receptors, Serotonin
  • Receptors, Serotonin, 5-HT1
  • Serotonin Receptor Agonists
  • Serotonin
  • 8-Hydroxy-2-(di-n-propylamino)tetralin
  • SK&F 82958