Synergistic interaction between serotonin-2 receptor and dopamine D1 receptor stimulation on striatal preprotachykinin mRNA expression in the 6-hydroxydopamine lesioned rat

Brain Res Mol Brain Res. 1999 Jun 18;70(1):125-34. doi: 10.1016/s0169-328x(99)00138-2.

Abstract

The regulation of striatal preprotachykinin (PPT) mRNA expression can be mediated through both dopamine (DA) D1 and serotonin (5-HT) 5-HT2A/2C receptors. In the present study, we used in situ hybridization to examine possible synergistic interactions between 5-HT2A/2C and D1 receptor-mediated regulation of striatal PPT mRNA levels in the rat depleted of DA with 6-hydroxydopamine. Acute administration of the 5-HT2A/2C receptor agonist DOI (2 mg/kg) significantly increased (+75%) PPT mRNA levels in the dorsal striatum. Acute administration of the D1 receptor agonist SKF-38393 (2 mg/kg) did not significantly alter PPT mRNA levels in the dorsal striatum. However, the co-administration of SKF-38393 and DOI produced a significant increase (+300%) in striatal PPT mRNA expression restricted to the periventricular region of the dorsal-medial striatum. This synergistic interaction was not observed in the remaining aspect of the dorsal striatum where DOI alone increased PPT mRNA expression. These data show that 5-HT2A/2C and D1 receptors can act in a synergistic manner to regulate striatal PPT mRNA in a subregion of the DA-depleted striatum.

Publication types

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

MeSH terms

  • 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / pharmacology*
  • Amphetamines / pharmacology*
  • Animals
  • Chromatography, High Pressure Liquid
  • Corpus Striatum / drug effects*
  • Corpus Striatum / metabolism
  • Denervation
  • Dopamine / pharmacology*
  • Dopamine Agonists / pharmacology*
  • Drug Synergism
  • Gene Expression Regulation / drug effects*
  • In Situ Hybridization
  • Male
  • Nerve Tissue Proteins / biosynthesis*
  • Nerve Tissue Proteins / genetics
  • Neurons / drug effects
  • Neurons / metabolism
  • Oxidopamine / toxicity*
  • Parkinson Disease, Secondary / chemically induced
  • Protein Precursors / biosynthesis*
  • Protein Precursors / genetics
  • RNA, Messenger / biosynthesis*
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, Serotonin, 5-HT2A
  • Receptor, Serotonin, 5-HT2C
  • Receptors, Dopamine D1 / drug effects
  • Receptors, Dopamine D1 / physiology*
  • Receptors, Serotonin / drug effects
  • Receptors, Serotonin / physiology*
  • Serotonin / pharmacology*
  • Serotonin Receptor Agonists / pharmacology*
  • Tachykinins / biosynthesis*
  • Tachykinins / genetics

Substances

  • Amphetamines
  • Dopamine Agonists
  • Nerve Tissue Proteins
  • Protein Precursors
  • RNA, Messenger
  • Receptor, Serotonin, 5-HT2A
  • Receptor, Serotonin, 5-HT2C
  • Receptors, Dopamine D1
  • Receptors, Serotonin
  • Serotonin Receptor Agonists
  • Tachykinins
  • preprotachykinin
  • Serotonin
  • 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine
  • Oxidopamine
  • 4-iodo-2,5-dimethoxyphenylisopropylamine
  • Dopamine