Central 5-HT4 receptors and dopamine-dependent motor behaviors: Searching for a functional role

Philippe De Deurwaerdère, Luigi Cervo, Luis Stinus, Umberto Spampinato

Research output: Contribution to journalArticle

Abstract

In this study, we evaluated the role of central 5-HT4 receptors in the control of motor behaviors related to change of nigrostriatal dopamine (DA) transmission, namely, stereotyped behavior and catalepsy in rats. Indeed, given that 5-HT4 receptors indirectly modulate nigrostriatal DA neuron activity, we hypothesized that these receptors would regulate nigrostriatal DA transmission in the basal ganglia, and consequently, associated motor responses. Stereotypy was induced either by an acute administration of apomorphine (0.3 and 1.5 mg/kg sc), or by a single morphine administration (15 mg/kg sc) in chronically morphine-treated (15 mg/kg sc, twice daily for 10 days) rats. Catalepsy was induced by the typical neuroleptic haloperidol (HAL; 1 mg/kg sc). The selective 5-HT4 antagonist, GR 125487 (1 mg/kg ip), modified neither apomorphine- nor morphine-induced stereotypy. HAL-induced catalepsy, while reduced by the systemic administration of the 5-HT1A agonist 8-OH-DPAT (0.1 mg/kg sc), was insensitive to GR 125487, systemically (1, 3, 10 mg/kg ip) or locally (20 and 40 nmol/20 μl) administered into the third ventricle. Also, HAL-induced catalepsy was not affected by the selective 5-HT4 antagonist GR 113808 (3 mg/kg ip). The obtained results indicate that 5-HT4 receptor antagonism does not modulate motor behaviors related to change of striatal DA transmission.

Original languageEnglish
Pages (from-to)627-633
Number of pages7
JournalPharmacology, Biochemistry and Behavior
Volume71
Issue number4
DOIs
Publication statusPublished - 2002

Keywords

  • 5-HT receptors
  • Apomorphine
  • Catalepsy
  • GR 113808
  • GR 125487
  • Haloperidol
  • Morphine
  • Stereotypy

ASJC Scopus subject areas

  • Biochemistry
  • Behavioral Neuroscience
  • Pharmacology

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